hepatitis c - Journal of the International AIDS Society

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Abstract supplement
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ONLINE
International Congress of Drug Therapy in HIV Infection
2–6 November 2014, Glasgow, UK
CO-MORBIDITIES AND COMPLICATIONS
ANTIRETROVIRAL
THERAPY
ADVERSE
EVENTS
ISSUES FOR HIV CARE
COST
EFFECTIVENESS
HEPATITIS C
NEW
HIV DRUGS
INITIATIVES
TREATMENT
PREVENTION HIV STRATEGIES
ART
ARV-BASED
30 YEARS OF
RESISTANCE HEALTHCARE
RESOURCES
ART AND REPRODUCTIVE HEALTH
AND TROPISM
STRATEGIES
COMMUNITY INFLAMMATION AND IMMUNE RECOVERY
VIROLOGY
FIRST LINE TREATMENT ISSUES
MANAGEMENT OF CO-MORBIDITIES
Joint Academic Sponsors
University College
London Medical School
(UCLMS), UK
Karolinska Institutet
Stockholm
Sweden
Volume 17, Supplement 3
November 2014
Academic Medical Centre
University of Amsterdam
The Netherlands
Weill Cornell Medical College
of Cornell University
New York, USA
International
AIDS Society
Scan this QR code with
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FSC® C020438
Abstract supplement
International Congress of Drug Therapy in HIV Infection
2–6 November 2014, Glasgow, UK
Contents
Keynote Lectures
1
Oral Abstracts
Inflammation and Immune Recovery Investing in the Future: T
he Work of The Congress HIV Research Trust
Art and Reproductive Health
Lock Lecture First Line Treatment Issues
Making Resources for Healthcare Count: What is The Optimal Way of Managing HIV?
Hepatitis C
When East Meets West: Issues for HIV Care Across Europe
Co-Morbidities and Complications Part I Co-Morbidities and Complications Part II
Resistance and Tropism
ARV-Based Prevention
ART Strategies
New HIV Drugs
2
3
4
5
6
7
9
10
14
18
21
23
23
26
Poster Abstracts
Adherence Adverse Events – Cardiovascular Adverse Events – Metabolic
Adverse Events – Renal
Adverse Events – Bone
Adverse Events – Other
Clinical Pharmacology
Community Initiatives Cost Effectiveness
Evaluation of ARV Delivery and Coverage
HIV-Related Infections, Co-Infections and Cancers, etc – Opportunistic Infections
HIV-Related Infections, Co-Infections and Cancers, etc – Opportunistic Tuberculosis
HIV-Related Infections, Co-Infections and Cancers, etc – Opportunistic Hepatitis Co-Infection (HCV and HBV)
HIV-Related Infections, Co-Infections and Cancers, etc – Cancers
HIV-Related Infections, Co-Infections and Cancers, etc – Others
Laboratory Monitoring of Disease and Therapy – General
Laboratory Monitoring of Disease and Therapy – Tropism Assays
Late Presenters
Volume 17, Supplement 3
November 2014
http://www.jiasociety.org/index.php/jias/issue/view/1470
29
36
42
48
53
56
64
69
76
82
87
89
90
101
106
115
126
128
Mother-To-Child Transmission
New Treatment and Targets
Non-AIDS Morbidities and Mortality, and Ageing
Pre- and Post- Exposure Prophylaxis and Treatment as Prevention
Resistance Treatment of Adolescents and Children
Treatment Strategies – Naïve Patients
Treatment Strategies – Experienced Patients
Treatment Strategies – Switch Studies
Treatment Strategies – Simplification Treatment Strategies – Other
130
135
136
148
152
164
165
176
181
190
201
Author Index
208
Abstracts of the HIV Drug Therapy Glasgow Congress 2014
Journal of the International AIDS Society 2014, 17 (Suppl 3)
http://www.jiasociety.org/index.php/jias/article/view/19856
KEYNOTE LECTURES
KL1
Curbing the epidemic on both sides of the Atlantic: a public
health perspective
Kevin Fenton
Health and Wellbeing, Public Health England, London, UK.
HIV/AIDS continues to place a devastating toll on individuals, families
and communities globally, and western industrialized countries are
by no means exempt. Today, there are more than 1 million Americans
and 100,000 Britons living with HIV, with a disproportionate burden
of new and prevalent HIV infections borne by gay, bisexual and
other men who have sex with men (MSM), racial/ethnic minorities,
migrants and persons who use drugs. Epidemic concentration in
urban areas, especially among: population sub-groups with high
prevalence of risk behaviours; the socio-economically marginalized;
or those with poor access to services, has been well documented.
Recent increases in HIV incidence in the rural south US, and in MSM
in both countries, reflect the dynamic and evolving nature of these
epidemics. New national HIV prevention strategies in both countries
have refocused attention on these domestic epidemics, prioritizing
HIV testing scaling up, linkage to quality care and tackling longstanding health inequalities. There are also significant differences
between the two countries in part a reflection of the different
health and social care systems; historical approaches to the funding
and coordination of HIV prevention; and underlying patterns of
health inequalities and their social and structural determinants.
In addition, the socialpolitical acceptability of using the sexual
health frame to guide more holistic and integrated approaches to
HIV prevention efforts remains a key difference. This presentation
will compare and contrast HIV prevention responses in the US and
UK over the past decade, identifying opportunities for enhancing
the prevention response in these and other western industrialized
countries in the 21st century.
http://dx.doi.org/10.7448/IAS.17.4.19476
KL2
Mechanisms underlying abnormalities of immune
activation/coagulation in HIV infection
Clifford Lane
Clinical and Molecular Retrovirology Section, National Institute of
Allergy and Infectious Diseases, National Institute of Health,
Bethesda, MD, USA.
Immune activation has been recognized as an important component
of the pathogenesis of HIV infection since the first recognition of
cases of AIDS in the early 1980s. Early in the AIDS epidemic, patients
with HIV infection were noted to have elevated levels of serum
immunoglobulins. CD38 expression on CD4 T cells was shown to be
an independent predictor of survival in 1999. The characterization of
HIV-associated immune activation has become progressively sophisticated over the past several years. A consistent finding has been
an association of poor clinical outcomes with markers of monocyte
activation (IL-6 and sCD14) and/or coagulation (D-dimer). These
relationships have been shown to exist even in patients with plasma
levels of HIV-1 B50 copies/ml. While it is generally accepted that
immune activation is related to HIV infection, there is less clarity
regarding the pathways that lead to its expression. Among the
forces reported to drive HIV-associated immune activation are innate
and adaptive immune responses to HIV and related co-infections,
homeostatic responses to CD4 T cell depletion and translocation
of microbial products across the intestinal wall. Recent work has
identified a potential role for ‘‘defective’’ HIV-1 transcripts in driving
immune activation. Studies examining the connections between the
adaptive immune system and the coagulation cascade have led
to the identification of PAR-1 as a potential target for therapeutic
intervention. Despite the successes experienced with cART, persistent immune activation in association with HIV infection remains a
scientific and clinical problem that is yet to be solved.
KL3
30 years of HIV: what have we learned?
Brian Gazzard
HIV Unit, Chelsea and Westminster Hospital, London, UK.
I saw my first patient with severe immune deficiency in 1979 a
very low CD4 count had been noted, but it was not until the first
reports of an epidemic occurred in 1981 that the correct diagnosis
was made. Subsequently, I have seen more than 15,000 patients with
HIV-related immune deficiency, and my life has changed from helping
terminally ill patients to die with dignity, in the early part of
the epidemic to now providing drugs for an eminently treatable
condition a true miracle. I have a number of observations about
the epidemic. Firstly, the courage with which many young people
faced death and disablement was truly awe inspiring, and was the
chief reason many of the earlier doctors treating these patients
stayed in the field. Secondly, the role of activists was overwhelmingly
positive forcing the epidemic to the top of the scientific and political
agenda and keeping it there. It is also important that activism helped
move an ethical agenda reducing the stigma of HIV infection and
producing a liberal legal framework which allowed testing and
treatment to be acceptable. The right of the world population to
health as espoused by Jonathan Mann and others is also crucial.
Thirdly, the combination of academic research, activist pressure (and
scientific input) and mammon in the form of the pharmaceutical
industry acting in concert produced knowledge which led to effective treatment in a breathtakingly short time. Particular tribute in
my mind needs to be paid to the pharmaceutical companies in
this regard. I believe that the scientific achievements of HIV research
illustrate two things. First, science builds from one generation to the
next and most (but not all of us) need to be humble about our
personal contribution. Second, HIV treatment illustrates the primacy
of well conducted randomized control trials. While cohort studies
can add to our detailed knowledge of the epidemic, randomised
controlled trials remain the cornerstone of most major advances.
Fourthly, when human beings act in concert towards a common goal,
amazing things can be achieved. In the late 1990s, the possibility of
treatment for the millions of people with HIV in the developing
world was seen as a distant dream. The present situation whilst not
perfect is a tribute to individuals, volunteers, government (particularly American government under President Bush) and personal
philanthropy (the Bill & Melinda Gates Foundation, and the Clinton
Foundation) that have used scientific knowledge to benefit the
global population.
1
Oral Abstracts
ORAL ABSTRACTS
O11 INFLAMMATION AND IMMUNE
RECOVERY
O111
Towards an HIV cure
Steven Deeks
AIDS Research Institute, University of California, San Francisco, CA, USA.
Given the challenge of delivering complex, expensive and potentially
harmful antiretroviral therapy (ART) on a global level, there is intense
interest in the development of short-term, well-tolerated regimens
that allow individuals to interrupt therapy indefinitely without
experiencing a rebound in viremia.This so-called ‘‘cure’’ or ‘‘remission’’
might be due to complete eradication of all replication-competent HIV
during ART or durable host-mediated control of persistent virus in
absence of ART. Recent heroic interventions such as hematopoietic
stem cell transplant and very early initiation of antiretroviral therapy
suggest that dramatic reductions in the reservoir size can be achieved,
but that complete eradication will be difficult if not impossible to
achieve. Most attempts to stimulate effective host-mediated control of HIV have failed. It is likely that for a true cure to be achieved,
both approaches reductions in the reservoir size and durable
immune surveillance will be needed, a state that is similar to
that observed in ‘‘elite’’ controllers and post-treatment controllers.
The implications for recent advances and setbacks in achieving HIV
remission for future research priorities will be discussed.
O112
Enhanced normalisation of CD4/CD8 ratio with early
antiretroviral therapy in primary HIV infection
John Thornhill1; Jamie Inshaw2; Soonita Oomeer1;
Pontiano Kaleebu3; David Cooper4; Gita Ramjee5; Mauro Schechter6;
Giuseppe Tambussi7; Julie Fox8; Jose Maria Miro9; Jonathan Weber1;
Abdel Babiker2; Kholoud Porter2 and Sarah Fidler1
1
Department of Medicine, Imperial College, London, UK. 2MRC
Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology,
London, UK. 3Medical Research Council, Uganda Virus Research
Institute, Entebbe, Uganda. 4Kirby Institute, University of New South
Wales, Sydney, Australia. 5HIV Prevention Unit, Medical Research
Council, Durban, South Africa. 6Hospital Escola Sao Francisco de
Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
7
Division of Infectious Diseases, Ospedale San Raffaele, Milan, Italy.
8
Guys and St Thomas’ NHS Trust, Kings College London, London, UK.
9
Hospital Clinic, University of Barcelona, Barcelona, Spain.
Introduction: Despite normalization of total CD4 counts, ongoing
immune dysfunction is noted amongst those on antiretroviral
therapy (ART). Low CD4/CD8 ratio is associated with a high risk of
AIDS and non-AIDS events and may act as a marker of immune
senescence [1]. This ratio is improved by ART although normalization
is uncommon ( 7%) [2]. The probability of normalization of CD4
count is improved with immediate ART initiation in primary HIV
infection (PHI) [3]. We examined whether CD4/CD8 ratio similarly
normalized in immediate vs. deferred ART at PHI.
Methods: Using data from the SPARTAC trial and the UK Register of
HIV Seroconverters, we examined the effect of ART with time
(continuous) from HIV seroconversion (SC) on CD4/CD8 ratio ( ]1)
adjusted for sex, risk group, ethnicity, enrolment from an African
site and both CD4 count and age at ART initiation. We also examined
that effect by dichotomizing HIV duration at ART initiation
(ART started within six months of SC: early ART; ART initiatedsix
months after SC: deferred). We also considered time to CD4 count
normalization ( ]900 cells/mm3).
Results: In total, 353 initiated ART with median (IQR) 97.9 (60.5, 384.5)
days from estimated seroconversion; 253/353 early ART, 100 deferred
ART. At one year after starting ART, 114/253 (45%) early ART had
normalized CD4/8 ratio, compared with 11/99 (11%) in the deferred
group, whilst 83/253 (33%) of early ART had normalized CD4 counts,
compared with 3/99 (3%) in the deferred group. Individuals initiating
within six months of PHI were significantly more likely to reach normal
ratio than those initiating later (HR, 95% CI 2.96, 1.755.01, pB0.001).
The longer after SC ART was initiated, the reduced likelihood of achieving normalization of CD4/CD8 ratio (HR 0.98, 95% CI 0.960.99 for
each 30-day increase). CD4 count at ART initiation was also associated
with normalization, as expected (HR 1.002, 95% CI 1.0011.002,
pB0.001). There was an association between normal CD4/CD8 ratio
and being virally suppressed (B400 copies HIV RNA/ml) pB0.001. CD4
count normalization was also significantly more likely for those initiating
early (HR 5.00, 95% CI 1.5216.41, p0.008).
Conclusions: The likelihood of achieving normalization of CD4/CD8 ratios
was increased if ART was initiated within six months of PHI. Higher CD4/
CD8 ratio may reflect a more ‘‘normal’’ immune phenotype conferring
enhanced prognosis and predict post-treatment control.
References
1. Serrano-Villar S, Perez-Elias MJ, Dronda F, Casado JL, Moreno A,
Royuela A, et al. Increased risk of serious non-AIDS-related events in
HIV-positive subjects on antiretroviral therapy associated with a low
CD4/CD8 ratio. PLoS One. 2014;9(1):85798.
2. Badura R, Antunes R, Janeiro N, Afonso C, Antunes F. What drives
a normal relation between T-CD4 and T-CD8? Tenth International
Congress on Drug Therapy in HIV Infection; Glasgow; 2010.
3. Le T, Wright EJ, Smith DM, He W, Catano G, Okulicz JF, et al.
Enhanced CD4 T-cell recovery with earlier HIV-1 antiretroviral
therapy. N Engl J Med. 2013;368(3):21830.
O113
CD4 cell count recovery in naı̈ve patients initiating cART,
who achieved and maintained plasma HIV-RNA suppression
Dominique Costagliola1; Jean-Marc Lacombe1; Jade Ghosn2;
Constance Delaugerre3; Gilles Pialoux4; Lise Cuzin5; Odile Launay6;
Amélie Ménard7; Pierre de Truchis8; Murielle Mary-Krause1;
Laurence Weiss9 and Jean-François Delfraissy10
1
INSERM and Sorbonne Universités, UPMC Paris Univ 06, Pierre Louis
Institute, UMR-S 1136, Paris, France. 2AP-HP, Hotel-Dieu, Université
Paris Descartes, Paris, France. 3AP-HP, Hôpital Saint-Louis, Université
Paris Diderot et INSERM, Paris, France. 4AP-HP, Hôpital Tenon, Service
de Maladies Infectieuses, Paris, France. 5CHU Toulouse, Service de
Maladies Infectieuses, Toulouse, France. 6AP-HP, Hôpital Cochin,
Fédération d’Infectiologie, Paris, France. 7AP-HM, Hôpital de la
Conception, Service de Maladies Infectieuses, Marseille,
France. 8AP-HP, Hôpital Raymond Poincaré, Service de Maladies
Infectieuses, Garches, France. 9AP-HP, Hôpital Européen Georges
Pompidou, Institut Pasteur, Paris, France. 10Agence Nationale de
Recherches sur le Sida et les Hépatites Virales, Paris, France.
2
Abstract O113Table 1.
cART initiation
Oral Abstracts
KM estimates of achieving a CD4 cell count 500/mm3 over time according to baseline CD4 cell count at
Baseline CD4cell count,
Median (IQR)
CD4B200 (n 5909), 100 [39156]
Year 1
8% (79)
Year 2
Year 3
Year 4
21% (2022) 33% (3134) 43% (4245)
Year 5
Year 6
Year 7
52% (5054) 60% (5861) 61% (5962)
200 5CD4B350 (n 5751), 269
[235305]
40% (3942) 61% (6062) 73% (7274) 81% (58082) 85% (8486) 88% (8789) 90% (8991)
350 5CD4B500 (n 2252), 404
74% (7276) 87% (8588) 91% (9092) 94% (9395)
95% (9396) 96% (9598) 97% (9598)
[374443]
Introduction: A key objective of combined antiretroviral therapy
(cART) is to reach and maintain high CD4 cell counts to provide
long-term protection against AIDS-defining opportunistic infections
and malignancies, as well as other comorbidities. However, a high
proportion of patients present late for care. Our objective was to
assess CD4 cell count recovery up to seven years in naı̈ve patients
initiating cART with at least three drugs in usual clinical care.
Methods: From the French Hospital Database on HIV, we selected
naı̈ve individuals initiating cART from 2000 with at least two years of
follow-up. Participants were further required to have achieved viral
load suppression by six months after initiating cART and were
censored in case of virological failure. We calculated the proportion
of patients (Kaplan-Meier estimates) who achieved CD4 recovery to
500/mm3 according to baseline CD4 cell count.
Results: A total of 15,025 patients were analyzed with a median
follow-up on ART of 65.5 months (IQR: 42.396.0). At cART initiation,
the median age was 38.6 years (IQR: 32.246.0), 9734 (64.8%) were
men, median CD4 cell count was 239 (IQR: 130336) and 2668
(17.8%) had a prior AIDS event. Results are presented in the Table 1.
Conclusions: This study shows that CD4 cell counts continue to
increase seven years after cART initiation, whatever the baseline
CD4 cell count. Failing to achieve CD4 recovery with continuous
viral load suppression is rare for naı̈ve patients initiating cART in
routine clinical practice, but takes substantially longer in patients
who initiate antiretroviral therapy at low CD4 cell counts.
O114
Determinants of IL-6 levels during HIV infection
Álvaro H Borges1; Jemma L O’Connor2; Andrew N Phillips2; Frederikke
F Rönsholt3; Sarah Pett4; Michael J Vjecha5; Martyn A French6 and
Jens D Lundgren1
1
Department Infectious Diseases & Rheumatology, CHIP,
Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
2
Research Department of Infection and Population, University
College London, London, UK. 3Department of Infectious Diseases,
4
MRC Clinical Trials Unit, UCL & Kirby Institute, University of
New South Wales Australia, London, UK. 5Veterans Affairs Medical
Center, Institute for Clinical Research, Washington, DC, USA.
6
Department of Clinical Immunology, Royal Perth Hospital &
PathWest Laboratory, Perth, Australia.
Introduction: Elevated IL-6 levels have been linked to increased
risk of cardiovascular disease (CVD), cancer and death. Compared to
the general population, treated HIV persons have 50100% higher
IL-6 levels, but few data on the determinants of IL-6 levels during HIV
infection currently exist.
Material and Methods: Participants in three international HIV trials
(SMART, ESPRIT and SILCAAT) with IL-6 plasma levels measured at
baseline were included (N 9864). Factors independently associated
with log2-transformed IL-6 level were identified by multivariate
linear regression; exponentiated estimates corresponding to fold
differences (FDs) in IL-6 were calculated. Demographics (age, gender,
race, BMI) and HIV-specific variables (nadir and entry CD4 counts,
HIV-RNA, use of different ART regimens) were investigated in
all three trials. In SMART (N4498), smoking, comorbidities (CVD,
diabetes, hepatitis B/C [HBV/HCV]), HDL-cholesterol, renal function
(eGFR) and educational level were also assessed.
Results: Demographics associated with higher IL-6 were older age (FD
[95% CI]: 1.09 [1.081.11] per 10 yr) and higher BMI (1.02 [1.01
1.04] per 5 kg/m2), whereas black race was associated with reduced
IL-6 (0.96 [0.930.99]). As for HIV variables, patients not receiving
ART (1.36 [1.291.43]) and with higher HIV-RNA (1.24 [1.011.52] for
100,000 vs. 5500 copies/mL) had increased IL-6. Participants
taking protease inhibitors (PI) had higher IL-6 (1.14[1.091.19]).
Higher nadir CD4 count (0.98 [0.970.99]/100 cells/mL) was related to
lower IL-6. All evaluated comorbidities were related to higher IL-6;
FDs in IL-6 were 1.08 [1.041.12] for smoking, 1.12 [1.021.24] for
CVD, 1.07 [1.001.16] for diabetes and 1.12 [1.021.24] for HBV (1.15
[1.021.30]) and 1.53 [1.451.62] for HCV. IL-6 increased with
decreasing eGFR (0.98 [0.971.00]/10 mL/min) and HDL-cholesterol
(0.98 [0.960.99]/10 mg/mL). Lower education was related to higher
IL-6 (1.09 [1.031.15] for high school vs. bachelor’s degree).
Conclusions: Higher IL-6 levels were associated with older age and
non-black race, higher BMI and lower HDL-cholesterol, ongoing HIV
replication, low nadir CD4 counts, comorbidities and decreased renal
function. This suggests that there are multiple causes of inflammation in treated HIV infection. A possible contribution from PI use was
also observed. Contribution from inflammation to explain variation
in clinical outcomes for these factors should be investigated.
O12 INVESTING IN THE FUTURE: THE
WORK OF THE CONGRESS HIV RESEARCH
TRUST
O121
Orphans of the HIV epidemic: the challenges from
toddlerhood to adolescence and beyond
Mamatha M Lala1,2
1
Pediatric Ward, Wadia Group and Hospital, Mumbai, India. 2Mumbai
Smiles, Mumbai, India.
This presentation focuses on the challenges and practical issues faced
each day by orphans of the HIV epidemic and the holistic care that
can be provided, as they continue to grow from toddlerhood to
adolescence and beyond. An HIV Research Trust Scholarship enabled
me to spend quality time in a sub-Saharan African province worst hit
by the HIV epidemic and to interact with local experts and learn
from mutual clinical experience. It was an immensely useful exercise
3
Oral Abstracts
as the clinical spectra of the diseases are very similar to ours and
they have ongoing active research programs very relevant to our
setting. India is arguably home to the largest number of orphans
of the HIV epidemic. The responsibility of caring for orphaned children overwhelms and pushes many extended families beyond their
ability to cope. Many countries are experiencing large increases in
the number of families headed by women and grandparents, or even
young children. These households are often unable to meet basic
needs, and so the number of children living on the streets is rising.
Orphaned children are disadvantaged in many devastating ways.
In addition to the trauma of witnessing the sickness and death of
one or both parents and perhaps siblings, they lack the necessary
parental guidance through crucial life-stages of identity formation
and transition into adulthood. They are more likely to suffer damage
to their cognitive and emotional development and be subjected to;
exploitation in terms of labour, social exclusion, extreme economic
uncertainty, physical and sexual abuse, illiteracy, malnutrition and
illness. Education remains a distant dream. With stigma and discrimination, they lack legal protection, lose inheritance rights, access
to essential services available to other community members and
professional help from doctors, teachers and lawyers. The implications for these unfortunate children are extraordinarily grave but
governments, international agencies, non-governmental organizations, schools, other community groups and individuals can still alter
the course of the crisis. The Committed Communities Development
Trust (CCDT) is a voluntary secular Trust, reaching out to 300,000
people annually, focusing intensively on children affected and infected
by HIV/AIDS, mainly orphans, child headed families, children living
in street situations, brothels, institutions and children at risk of
drug addiction, abuse and exploitation in Mumbai. We run several
comprehensive HIV/AIDS programmes addressing issues of prevention, care, support, education, awareness, empowerment, training
and research through strongly structured home-based care programs,
community based programs and temporary residential shelters. The
CCDT recognizes and understands the daunting challenges these
children face and helps them overcome these as a team by providing
comprehensive care and support, giving them an opportunity in life
and enabling them to become productive citizens of tomorrow.
University College of Health Sciences, Kampala, Uganda. 3Division of
Infectious Diseases, Feinberg School of Medicine, Northwestern
University, Chicago, IL, USA. 4Department of Molecular and Clinical
Pharmacology, University of Liverpool, Liverpool, UK. 5Department of
Pharmacology and Therapeutics, Trinity College Dublin, Dublin, Ireland.
Introduction: Sub-dermal hormone implants, such as levonorgestrel
(LNG), are a safe and desirable form of long-acting contraception, but
their use among HIV-positive women on antiretroviral therapy (ART)
may be compromised given the potential for a cytochrome P450 3Amediated drugdrug interaction. Our study aimed to characterize
the pharmacokinetics of LNG released from a sub-dermal implant
over six months in HIV-positive Ugandan women on nevirapine
(NVP)- or efavirenz (EFV)-based ART.
Material and Methods: This non-randomized, parallel group study
compared LNG pharmacokinetics between HIV-positive Ugandan
women not yet eligible for ART (control group, n 18) and those
on stable NVP- (n 20) or EFV- (n 20) based ART. The two-rod (75
mg/rod) LNG sub-dermal implant was inserted at study enrolment.
LNG sampling was obtained pre-implant and at weeks 1, 4, 12 and 24
post-insertion. LNG concentrations were analyzed using a validated
LC-MS/MS method, with an assay calibration range of 501500 pg/
mL. Safety monitoring, including a pregnancy test, was conducted at
each study visit.
Results: At enrolment, participants had a mean age of 31 years;
CD4 cell counts were similar between the control, NVP and EFV
groups (758, 645 and 568 cells/mm3, respectively; p0.09); all
women in the NVP and EFV groups had an undetectable HIV-RNA.
Women in the control group had a higher baseline body weight (73
kg) compared to those in the NVP (63 kg; p 0.03) or EFV groups (60
kg; pB0.01). By linear regression, weight was a significant predictor
of LNG concentrations (1 kg increase in weight 5 pg/mL decrease
in LNG, p0.03). LNG concentrations are reported in the table.
Conclusions: Over a 24-week period, LNG concentrations were 4054%
lower in women on EFV-based ART, despite their having a significantly
lower body weight, compared to those not on ART. In women on NVPbased ART, LNG concentrations were 3239% higher than those
observed in the control group, a difference partially explained by
body weight. These data confirm a significant drug interaction occurs
between the LNG implant and EFV, adding to growing concern for
reduced contraceptive efficacy with their combined use. In contrast,
these data support use of the LNG implant with NVP-based ART.
O13 ART AND REPRODUCTIVE HEALTH
O131
O132
Efavirenz- but not nevirapine-based antiretroviral therapy
decreases exposure to the levonorgestrel released from a
sub-dermal contraceptive implant
Darunavir pharmacokinetics throughout pregnancy and
postpartum
Kimberly Scarsi1; Mohammed Lamorde2; Kristin Darin3; Sujan Dilly
Penchala4; Laura Else4; Shadia Nakalema2; Pauline Byakika-Kibwika2;
Saye Khoo4; Susan Cohn3; Concepta Merry5 and David Back4
1
Department of Pharmacy Practice, University of Nebraska Medical
Center, Omaha, NE, USA. 2Infectious Diseases Institute, Makerere
John Lambert1; Valerie Jackson1; Laura Else2; Mairead Lawless1;
Grainne McDonald3; Dave Le Blanc3; Anjali Patel4; Kelly Stephens4
and Saye Khoo5
1
Infectious Diseases, The Rotunda Hospital, Dublin, Ireland.
2
Bioanalytical Facility, Royal Liverpool University Hospital, Liverpool,
UK. 3Department of Laboratory Medicine, The Rotunda Hospital,
Abstract O131Table 1. LNG concentrations shown as geometric mean (GM) with 90% confidence intervals (CIs)
Control group; pg/mL
NVP group; pg/mL
NVP:control GM ratio (90% CI) EFV group; pg/mL EFV:control GM ratio (90% CI)
Week 1
1003 (720, 1286)
1326 (1073, 1579)
1.32 (1.22, 1.49)
462 (370, 553)
0.46 (0.43, 0.51)
Week 4
629 (496, 761)
866 (737, 995)
1.38 (1.31, 1.48)
349 (268, 429)
0.55 (0.54, 0.56)
Week 12
547 (433, 661)
758 (656, 860)
1.39 (1.30, 1.52)
326 (268, 386)
0.60 (0.58, 0.62)
Week 24
500 (394, 605)
679 (569, 790)
1.36 (1.30, 1.44)
280 (208, 353)
0.56 (0.53, 0.58)
During this 24-week period, no participant discontinued the LNG implant due to adverse events and no pregnancy events occurred.
4
Dublin, Ireland. 4Catherine McAuley Clinical Research Centre,
Mater Misericordiae University Hospital, Dublin, Ireland. 5Molecular
and Clinical Pharmacology, Royal Liverpool University Hospital,
Liverpool, UK.
Introduction: Antiretroviral therapy is recommended during pregnancy
for prevention of mother-to-child transmission (MTCT) of HIV. Physiological changes during pregnancy are known to affect the pharmacokinetics (PK) of protease inhibitors (PIs), leading to lower exposures in
pregnant women. Here we examine the PK of DRV/r 800/100 mg once
daily (OD) over the course of pregnancy and postpartum (PP).
Materials and Methods: In this prospective open-labelled study,
HIV-positive pregnant women receiving darunavir/ritonavir as part of
their routine maternity care were enrolled. DRV plasma trough
concentrations [DRV] were determined in the first (T1) and/or
second (T2) and/or third (T3) trimester and PP using a validated
HPLC-MS/MS methodology (Lab21, Cambridge UK). Where possible
paired maternal and cord blood samples were taken at delivery.
Results: To date 20 women (12 black African, 8 Caucasian) have been
enrolled. Median (range) baseline CD4 count was 338 cells/mL (108
715), and median baseline plasma viral load was 555 copies/mL
( B408,188,943). All but 2 women were virally suppressed at time
of delivery (114 and 176 copies/mL; 1 sub-therapeutic at T3) and
median CD4 count was 410 cells/mL (92947). There were 20 live
births, all term deliveries and there were no cases of MTCT. [DRV]
(geometric mean; 95% CI) was 3790 ng/mL at T1 (n 1); 1288 ng/mL
(6631913) at T2 (n 9); 1086 ng/mL (7451428) at T3 (n18, 1
undetectable) and 2324 ng/mL (13693279) at PP (n 14, 1
undetectable). There was no significant difference in [DRV] between
T2 and PP (p 0.158); however, there was between T3 and PP
(p 0.021). Nineteen of twenty (95%) and 16 of 20 (80%) women
achieved [DRV] above the estimated MEC for WT (55 ng/mL) and
PI resistant HIV-1 (550 ng/mL) throughout pregnancy. Maternal
and cord [DRV] were available for 10 motherbaby pairs. Mean
maternal [DRV] at delivery was 2235 ng/mL (91557 ng/mL), while
mean cord [DRV] was 337 ng/mL (9217 ng/mL). The median cord to
maternal blood ratio (C/M) was 0.11 (0.060.49).
Conclusions: In most cases examined, DRV/r 800/100 mg once daily
was effective at achieving adequate therapeutic drug levels ( 550
ng/ml) during pregnancy. However, reduced DRV plasma concentrations in the second/third trimesters highlights the need for TDM in
this population and warrants further study of pregnancy-associated
changes in DRV pharmacokinetics. The low C/M ratios reported here
are consistent with previous reports [1] and suggest low transplacental transfer of DRV.
Reference
1. Else LJ, Taylor S, Back DJ, Khoo SH. Pharmacokinetics of antiretroviral drugs in anatomical sanctuary sites: the fetal compartment
(placenta and amniotic fluid). Antivir Ther. 2011;16(8):113947.
O133
Does pregnancy increase the risk of ART-induced
hepatotoxicity among HIV-positive women?
Susie Huntington1; Claire Thorne2; Jane Anderson3; MarieLouise Newell4; Graham Taylor5; Deenan Pillay1; Teresa Hill1;
Pat Tookey2 and Caroline Sabin1
1
Department of Infection & Population Health, UCL, London, UK.
2
Population, Policy and Practice Programme, UCL Institute of Child
Health, London, UK. 3Centre for the Study of Sexual Health and HIV,
Homerton University Hospital NHS Foundation Trust, London, UK.
4
Human Development and Health, University of Southampton,
Southampton, UK. 5Faculty of Medicine, Imperial College,
London, UK.
Oral Abstracts
Introduction: High rates of hepatotoxicity have been observed
among HIV-positive pregnant women using antiretroviral therapy
(ART). However, the extent to which pregnancy affects the risk of
ART-induced hepatotoxicity is unclear since studies in this area have
generated conflicting results.
Materials and Methods: Combined data from the UK Collaborative
HIV Cohort (UK CHIC) study and the UK and Ireland National Study
of HIV in Pregnancy and Childhood (NSHPC) were used. Alanine
aminotransferase (ALT) data were assessed according to the Division
of AIDS toxicity guidelines to identify factors associated with liver
enzyme elevation (LEE) (grade 14). Women starting ART in 200011
aged 1649 years were included irrespective of pregnancy status
at ART start. Cox proportional hazards were used to assess the
associations between fixed (ethnicity, exposure group, HBV/HCV coinfection, prior ART use, and age, year, pregnancy status, viral
load and CD4 count at ART start) and time-dependent covariates
(pregnancy status, age, year, CD4 count, viral load, duration on ART)
and the risk of LEE.
Results: Of the 3426 women included, one-quarter (25.0%, n 857)
were pregnant during follow-up and 14.4% (n 492) started ART
during pregnancy. The rate of LEE was 15/100 person-years (PY)
during pregnancy and 6.1/100 PY outside pregnancy. The risk of LEE
was increased during pregnancy (adjusted hazard ratio (aHR) 1.61
[1.262.06], p B0.001), including in secondary analysis excluding
493 women pregnant when starting ART. Other factors independently associated with LEE were lower CD4 count ( B250 cells/mm3
vs. 251350 cells/mm3 aHR 1.25 [1.021.54], p 0.03), HBV/HCV coinfection (aHR 1.94 [1.582.39], p B0.001), HIV acquired via injecting
drug use (aHR 1.61 [1.152.24], p 0.01 vs. heterosexually) and
calendar year (aHR 1.05 [1.021.08], p B0.001 per one year
increase). Three ART drugs were associated with increased risk of
LEE (efavirenz aHR 1.27 [1.061.50], p-value 0.008; maraviroc
4.19 [1.3413.1], p 0.01; and nevirapine 1.59 [1.301.95], p-value
B0.001). Use of zidovudine was associated with decreased risk of
LEE (aHR 0.74 [0.630.87], p B0.001) as was increasing time on an
NNRTI-based regimen (aHR 0.91 [0.860.96], p B0.001 per additional year).
Conclusions: Pregnant women were at increased risk of LEE,
highlighting the importance of close monitoring of toxicity biomarkers during pregnancy.
O14 LOCK LECTURE
O141
From guidelines to action: implementation opportunities
and realities
Wafaa El-Sadr
ICAP, Columbia University, New York, NY, USA.
The past decade has seen notable progress in confronting the
HIV epidemic. By the end of 2013, almost 13 million persons living
with HIV had access to antiretroviral therapy (ART) in low- and
middle-income countries (LMIC). In addition, progress has also been
achieved in terms of HIV prevention with 26 LMIC achieving a
50% decrease in number of new infections including 15 countries
in sub-Saharan Africa. New research findings also offer new
efficacious prevention interventions that offer new opportunities
for further mitigation of new HIV infections. Such progress has
inspired ambitious pronouncements such as achieving ‘‘The End
of AIDS’’ or ‘‘An AIDS Free Generation.’’ This progress has also
motivated the development of new guidelines aimed to achieving these goals. Implementation of guideline recommendations,
5
Oral Abstracts
however, requires translation of these guidelines into actionable
steps and then their successful delivery within established health
services. The opportunities offered by new guidelines frequently
meet the realities of the frailties of the health system. Achieving
current ambitious global targets must confront the specific deficits
in the health system that inhibit access and acceptability of programmes as well as hinder achievement of high quality or desired
coverage.
approach of using two new classes for second line when standard first-line therapy has failed, which avoids resistance genotyping. Notwithstanding, adherence must be stressed in those
failing first-line treatments. Protease inhibitor monotherapy is not
suitable for a public health approach in low- and middle-income
countries.
O153
O15 FIRST LINE TREATMENT ISSUES
O151
Choice of initial therapy
Manuel Battegay
Division of Infectious Diseases & Hospital Epidemiology, University
Hospital Basel, Basel, Switzerland.
Current international and national treatment guidelines such as EACS,
BHIVA, DHHS or IAS update regularly recommendations on
the choice of initial combination antiretroviral treatment (cART)
regimens. Preferred cART regimens include a backbone with two
nucleoside (nucleotide) reverse transcriptase inhibitors combined
either with one non-nucleoside reverse transcriptase inhibitor or
one ritonavir boosted protease inhibitor or more recently one
integrase inhibitor. Response rates according to viral load measurements increased in recent years, in particular due to better tolerability.
The choice of initial therapy is flexible and influenced by several factors
such as height of viral load, genotypic resistance testing, CD4
cell count, co-morbidities, interactions, potential adverse events,
(potential for) pregnancy, convenience, adherence, costs as well as
physician’s and patient’s preferences. Diverse highly potent initial
cART regimens exist. Following the many possibilities, the choice
of a regimen is based on a mixture of evidence-informed data and
individualized concepts, some of the latter only partly supported by
strong evidence. For example, different perceptions and personal
experiences exist about boosted protease inhibitors compared to nonnucleoside reverse transcriptase inhibitors or integrase inhibitors and
vice versa which may influence the initial choice. This lecture will
discuss choices of initial cART in view of international guidelines and
the evidence for individualization of initial HIV therapy.
O152
Managing first-line failure
David A Cooper
Kirby Institute, University of New South Wales, Sydney, Australia.
WHO standard of care for failure of a first regimen, usually 2N(t)
RTI’s and an NNRTI, consists of a ritonavir-boosted protease inhibitor with a change in N(t)RTI’s. Until recently, there was no
evidence to support these recommendations which were based
on expert opinion. Two large randomized clinical trials, SECOND
LINE and EARNEST both showed excellent response rates ( 80%)
for the WHO standard of care and indicated that a novel regimen
of a boosted protease inhibitor with an integrase inhibitor had
equal efficacy with no difference in toxicity. In EARNEST, a third
arm consisting of induction with the combined protease and
integrase inhibitor followed by protease inhibitor monotherapy
maintenance was inferior and led to substantial (20%) protease
inhibitor resistance. These studies confirm the validity of the current
recommendations of WHO and point to a novel public health
Once-daily dolutegravir is superior to once-daily darunavir/
ritonavir in treatment-naı̈ve HIV-1-positive individuals:
96 week results from FLAMINGO
Jean-Michel Molina1; Bonaventura Clotet2; Jan van Lunzen3;
Adriano Lazzarin4; Matthias Cavassini5; Keith Henry6;
Valeriv Kulagin7; Naomi Givens8; Clare Brennan9 and Carlos
Fernando de Oliveira10
1
Service des Maladies, Infectieuses et Tropicales, Hôpital Saint
Louis, Paris, France. 2HIV Unit, Hospital Universitari Germans Trias i
Pujol, Irsicaixa Foundation, UAB, UVIC-UCC, Badalona, Catalonia,
Spain. 3Infectious Diseases Unit, University Medical Center HamburgEppendorf, Hamburg, Germany. 4Department of Infectious Diseases,
IRCCS San Raffaele Via Stamira d’Ancona, Milan, Italy. 5Infectious
Disease Service, Lausanne University Hospital, Lausanne, Switzerland.
6
Department of Medicine, Hennepin County Medical Center,
Minneapolis, MN, USA. 7Clinical Center for Prevention and Control
of AIDS, Krasnodar, Russian Federation. 8Clinical Statistics,
GlaxoSmithKline, Stockley Park, UK. 9Infectious Diseases,
GlaxoSmithKline, Clinical Development, Research Triangle Park, NC,
USA. 10PPD, Pharmacovigilance, Morrisville, NC, USA.
Introduction: Dolutegravir (DTG) 50 mg once daily was superior
to darunavir/ritonavir (DRV/r) 800 mg/100 mg once daily through
Week 48, with 90% vs. 83% of participants achieving HIV RNA 50 c/
mL (p 0.025)[1]. We present data through Week 96.
Materials and Methods: FLAMINGO is a multicentre, randomized,
open-label, Phase IIIb non-inferiority study, in which HIV-1-positive
ART-naı̈ve adults with HIV-1 RNA ]1000 c/mL and no evidence of
viral resistance were randomized 1:1 to receive DTG or DRV/r, with
investigator-selected backbone NRTIs (TDF/FTC or ABC/3TC). Participants were stratified by screening HIV-1 RNA ( 5100K c/mL) and
NRTI backbone.
Results: A total of 484 adults were randomized and treated; 25% had
baseline HIV RNA 100K c/mL. At Week 96, the proportion of
participants with HIV RNA 50 c/mL was 80% in the DTG arm vs.
68% in the DRV/r arm (adjusted difference 12.4%; 95% CI 4.7, 20.2%;
p 0.002). Secondary analyses supported primary results: perprotocol [(DTG 83% vs. DRV/r 70%, 95% CI 12.9 (5.3, 20.6)] and
treatment-related discontinuation failure [(98% vs. 95%, 95% CI
3.2 ( 0.3, 6.7)]. Overall virologic non-response (DTG 8%; DRV/r
12%) and non-response due to other reasons (DTG 12%; DRV/r 21%)
occurred less frequently on DTG. As at Week 48, the difference
between arms was most pronounced in participants with high
baseline viral load (82% vs. 52% response through Week 96) and in
the TDF/FTC stratum (79% vs. 64%); consistent responses were seen
in the ABC/3TC stratum (82% vs. 75%). Six participants (DTG 2, none
post-Week 48; DRV/r 4, two post-Week 48) experienced protocoldefined virologic failure (PDVF; confirmed viral load 200 c/mL on
or after Week 24); none had treatment-emergent resistance to
study drugs. Most frequent drug-related adverse events (AEs)
were diarrhoea, nausea and headache, with diarrhoea significantly
more common on DRV/r (24%) than DTG (10%). Significantly more
participants had Grade 2 fasting LDL toxicities on DRV/r (22%)
vs. DTG (7%), p B0.001; mean changes in creatinine for DTG
( 0.18 mg/dL) observed at Week 2 were stable through Week 96.
6
Conclusions: Once-daily DTG was superior to once-daily DRV/r in
treatment-naı̈ve HIV-1-positive individuals, with no evidence of
emergent resistance to DTG in virologic failure and relatively similar
safety profiles for DTG and DRV/r through 96 Weeks.
Oral Abstracts
call for the use of generic 3TC, a well-powered randomized trial to
confirm the presumed equivalence of 3TC and FTC is needed.
Reference
1. Clotet B, Feinberg J, van Lunzen J, et al. Once-daily dolutegravir
is superior to Darunavir ritonavir in antiretroviral naı̈ve adults
with HIV-1 Infection: 48 week results from the randomised study
ING114915. Lancet. Published Online April 1, 2014. http://dx.doi.
org/10.1016/S0140-6736(14)60084-2
O21 MAKING RESOURCES FOR
HEALTHCARE COUNT: WHAT IS THE
OPTIMAL WAY OF MANAGING HIV?
O211
O154
More virological failure with lamivudine than emtricitabine
in efavirenz and nevirapine regimens in the Dutch
nationwide HIV Cohort
Casper Rokx1; Azzania Fibriani2; David van de Vijver2; Annelies
Verbon1; Martin Schutten2; Luuk Gras3 and
Bart JA Rijnders1
1
Department of Internal Medicine, Erasmus University Medical
Center, Rotterdam, Netherlands. 2Department of Virology, Erasmus
University Medical Center, Rotterdam, Netherlands. 3On behalf of
the ATHENA national observational cohort study. Dutch HIV
Monitoring Foundation, Research Department, Amsterdam,
Netherlands.
Introduction: Lamivudine (3TC) and emtricitabine (FTC) are considered interchangeable by HIV-1 guidelines in first-line tenofovir/
efavirenz (TDF/EFV) and TDF/nevirapine (NVP) combination antiretroviral therapy (cART). Data from trials on equivalence of 3TC and
FTC are inconsistent. We examined the effectiveness of 3TC and FTC
in the national HIV cohort in the Netherlands.
Materials and Methods: Observational cohort study on cART naı̈ve
HIV-1 patients. Therapy was initiated as 3TC or FTC with TDF/EFV
or TDF/NVP between 2002 and 2012. Patients with baseline
resistance or prior cART experience were excluded. Main outcomes
were Week 48 virological failure (VF) by on treatment analysis,
time to HIV-RNA B400 copies/mL within 48 weeks and VF within
240 weeks after at least one HIV-RNA B400 copies/mL. Acquired
resistance to reverse transcriptase was evaluated. Analyses were
done by logistic regression and Cox proportional hazard models.
Propensity score adjusted models and intention to treat evaluations
were included as sensitivity analysis.
Results: A total of 4836 patients initiated 3TC/TDF/EFV (n546),
FTC/TDF/EFV (n 3391), 3TC/TDF/NVP (n 207) or FTC/TDF/NVP
(n 692). Ninety-six patients were excluded for baseline resistance or
prior cART experience. By Week 48, VF proportions were higher for
3TC/TDF/EFV (10.8%) compared to FTC/TDF/EFV (3.6%) and for 3TC/
TDF/NVP (27.0%) compared to FTC/TDF/NVP (11.0%). The multivariable adjusted odds ratio (OR) on VF was 1.78 (95% CI 1.112.84;
p 0.016) with 3TC/TDF/EFV compared to FTC/TDF/EFV and 2.09 (95%
CI 1.253.52; p 0.005) with 3TC/TDF/NVP compared to FTC/TDF/
NVP. Propensity score adjusted models and intention to treat analyses
showed comparable results. The time to virological suppression within
48 weeks was not influenced by using 3TC or FTC in cART. If HIV-RNA
B400 copies/mL was achieved on initial cART first, no differences in
VF within 240 weeks were observed between 3TC and FTC with TDF/
EFV (p 0.090) or TDF/NVP (P 0.255). Patients failing 3TC-containing cART had higher median HIV-RNA at VF compared to FTC
containing cART (p B0.001) and 89.8% had acquired resistance on
3TC compared to 81.2% on FTC.
Conclusions: Including FTC in cART is associated with better
virological responses compared to 3TC. As cost constraints may
Rational allocation of resources available for healthcare:
understanding cost effectiveness analyst
Andrew Briggs
Health Economics & Health Technology Assessment, Institute of
Health & Wellbeing, University of Glasgow, Glasgow, UK.
Health systems around the world are grappling with the difficult issue
of how to allocate scare healthcare resources. Within Europe many
different approaches to healthcare resource allocation exist, but it is
clear that the formal techniques of cost-effectiveness analysis are
becoming increasingly important. This presentation will first address
the fundamental economic principles of scarcity and opportunity cost,
before looking at how different European systems are attempting to
address the economic challenge of providing healthcare for their
population from a limited budget. The presentation will go on to
consider general issues in health economic evaluation that are likely
important for clinical community focused on HIV treatment: appropriate
comparator treatments for defining opportunity cost, patient heterogeneity and the potential for personalized/stratified medicine to control
costs and target treatment appropriately.
O212
The challenge: streamlining HIV treatment and care while
improving outcomes
Nathan Clumeck
Division of Infectious Diseases, Saint Pierre University Hospital,
Brussels, Belgium.
ART coverage among HIV-positive population varies, depending
on the countries, between 10% (e.g. Indonesia) and 65% (Botswana).
Death rates and new HIV infections have been linked to ART coverage.
Therefore, streamlining tasks and roles to expand treatment and care
and to provide quality and equitable health is an ongoing concern
globally. One concept that has been applied to improve the delivery of
HIV services is that of task shifting. Defined as the systematic delegation
of tasks from doctors to cadre with less training such as nurses or lay
workers, task shifting has been used as an effective strategy to address
the current healthcare worker shortage in many African countries.
A body of literature supports the use of task shifting as a successful approach in delivering healthcare services including HIV testing,
counselling and ART treatment. In addition, in a time of economic
burden and scare resources, task shifting may also help to relieve the
situation. This concern is highlighted in recommendation of WHO to
strengthen and expand human capacity among healthcare workers. The
major issues that are raised are: How can task shifting be implemented
in a way that is sustainable? How can clinical care services be organized
to maximize the potential of the task-shifting approach while ensuring
safety, efficiency and effectiveness? What preconditions must be met,
what are the country-specific factors that will guide decision-making in
the implementation of task shifting? In addition, task shifting should
be implemented alongside other efforts to increase the numbers of
7
skilled health workers. Quality assurances mechanisms should provide
the necessary checks balances to protect both service users and health
workers.
O213
Models of care and delivery
Jens Lundgren
Copenhagen HIV Programme, University of Copenhagen,
Copenhagen, Denmark.
Oral Abstracts
stigmatized long-term chronic condition and rely on the nurse as a
point of contact to access advice and support readily. The more
chaotic and vulnerable clients with complex care needs require the
nurse to co-ordinate their care, ensuring the appropriate agencies
remain involved. Overseeing the transition of care to other units
and tracing patients who are lost to follow up is also a necessity,
as retention in care is paramount for the continued improvement
in clinical outcomes. The contribution that specialist nurses make to
the provision of HIV care is valuable and will continue to play a large
role in the delivery of such care.
Marked regional differences in HIV-related clinical outcomes exist
across Europe. Models of outpatient HIV care, including HIV testing,
linkage and retention for positive persons, also differ across the
continent, including examples of sub-optimal care. Even in settings
with reasonably good outcomes, existing models are scrutinized for
simplification and/or reduced cost. Outpatient HIV care models across
Europe may be centralized to specialized clinics only, primarily handled
by general practitioners (GP), or a mixture of the two, depending on
the setting. Key factors explaining this diversity include differences
in health policy, health insurance structures, case load and the
prevalence of HIV-related morbidity. In clinical stable populations,
the current trend is to gradually extend intervals between HIV-specific
visits in a shared care model with GPs. A similar shared-model approach with community clinics for injecting drug-dependent persons is
also being implemented. Shared care models require oversight to
ensure that primary responsibility is defined for the persons overall
health situation, for screening of co-morbidities, defining indication to
treat comorbidities, prescription of non-HIV medicines, etc. Intelligent
bioinformatics platforms (i.e. generation of alerts if course of care
deviates from a prior defined normality) are being developed to assist
in providing this oversight and to provide measure of quality. Although
consensus exists to assess basic quality indicators of care, a comprehensive set of harmonized indicators are urgently needed to define
best practise standards via benchmarking. Such a tool will be central to
guide ongoing discussions on restructuring of models, as quality of care
should not be compromised in this process.
O215
O216
O214
Predicted savings to the UK National Health Service from
switching to generic antiretrovirals, 20142018
Integrated care pathways and task shifting
Linda Panton
Regional Infectious Diseases Unit, Western General Hospital,
Edinburgh, UK.
Delivery of HIV care has evolved over the last 10 years, and nurse
specialists are a driving force in developing new pathways to
enhance patient care. Despite the continued rise in numbers of
people living with HIV, the financial constraints on the NHS have
unfortunately resulted in a reduction in service provision. Experienced nurses are integral to patient care management. They not only
provide standardized care for stable patients, therefore increasing consultant capacity for the more complex medical patient, but
have a degree of flexibility that allows newly diagnosed patients
quick access to care and support. With a strong emphasis being
placed on an integrated and collaborative multidisciplinary team
approach, to ensure patients receive the same standard of care,
Scotland’s HIV centres follow an integrated care pathway. The nurse
oversees the completion of this document and co-ordinates the
pathway of care depending on the clinical need. Nurses develop and
maintain necessary partnerships between primary care, specialist
care, psychological services, social care and third sector support
services. The nurse case load continues to expand and diversify.
Stable patients may be maintained on therapy but are living with a
Enhancing patient self-management
Alain Volny-Anne
Paris, France.
In the context of HIV as a chronic disease, care being delivered with
more constrained budgets and being more complex as many patients
are ageing, the need for disease self-management is increasingly
recognized. Like in other chronic diseases, HIV care and treatment
guidelines increasingly promote the enhancement of health management by patients, within a framework of closer collaboration with
their healthcare providers. Therefore, patients progressively become
key resources on which health systems should count for efficiency
and improvement. Is this a principle or is this reality? We are aware
that to count in healthcare, resources must be allocated the
necessary support. How does the required support translate into
patients’ real lives? Do patient education programmes respond
adequately to these needs? Are chronic care models really applicable
in contexts where care is not yet sufficiently coordinated, especially
with regards to people who are ageing with HIV and the multiple
types of care they need? How far should a patient take responsibility
for making best of healthcare resources? From the perspective of
a person living and ageing with HIV, the role of patients in the
management of their own health will be discussed.
Andrew Hill1; Teresa Hill2; Sophie Jose2 and Anton Pozniak3
1
Department of Pharmacology and Therapeutics, University of
Liverpool, Liverpool, UK. 2Department of Infection and Population
Health, University College, London, UK. 3St Stephens Centre, Chelsea
and Westminster Hospital, London, UK.
Introduction: In other disease areas, generic drugs are normally used
after patent expiry. Patents on zidovudine, lamivudine, nevirapine
and efavirenz have already expired. Patents will expire for abacavir in
late 2014, lopinavir/r in 2016, and tenofovir, darunavir and atazanavir
in 2017. However, patents on single-tablet regimens do not expire
until after 2026.
Methods: The number of people taking each antiretroviral in the UK
was estimated from 23,655 individuals in the UK CHIC cohort (2012
database). Costs of patented drugs were taken from the British
National Formulary database, assuming a 30% discount. Costs of
generic antiretrovirals were estimated using an 80% discount from
patented prices, or actual costs where available. Two options were
analysed: 1 all patients use single-tablet regimens and patented
versions of drugs; prices remain stable over time; 2 all people
switch from patented to generic drugs when available, after patent
expiry (dates shown above).
Results: There were an estimated 67,000 people taking antiretrovirals in the UK in 2014, estimated to rise by 8% per year until 2018
8
(in line with previous rises). The most widely used antiretrovirals in
the CHIC cohort were tenofovir (TDF) (75%), emtricitabine (FTC)
(69%), efavirenz (EFV) (39%), lamivudine (3TC) (23%), abacavir (ABC)
(18%), darunavir (DRV) (21%) and atazanavir (ATV) (16%). The
predicted annual UK cost of generic ABC/3TC/EFV (three generic
tablets once daily) was £1018 per person-year. Costs of patented
single-tablet regimens ranged from £5000 to £7500 per person-year.
Assuming continued use of patented antiretrovirals in the UK, the
predicted total national costs of antiretroviral treatment were
predicted to rise from £425 million in 2014 to £459 m in 2015,
£495 m in 2016, £536 m in 2017 and £578 m in 2018. With a 100%
switch to generics, total predicted costs were £337 m in 2014, £364
m in 2015, £382 m in 2016, £144 m in 2017 and £169 m in 2018. The
total predicted saving over five years from a switch to generics was
£1.1 billion.
Conclusions: Systematic switching from patented to generic antiretrovirals could potentially save approximately £1.1 billion in the UK
over the next five years, compared with continued use of patented
versions: this money could be spent on urgently needed HIV prevention programmes. Similar savings are feasible for other European
countries, given parallel patent expiry dates. More detailed economic
evaluation is required to show when patented single-tablet regimens
provide value for money, compared to bioequivalent generic versions
of 34 pills once daily.
O217
Cost-effectiveness analysis of protease inhibitor
monotherapy vs. ongoing triple-therapy in the long-term
management of HIV patients
Lars Oddershede1; Simon Walker2; Nicholas Paton3; Wolfgang Stöhr3;
David Dunn3 and Mark Sculpher2
1
Danish Center for Healthcare Improvements, Aalborg University,
Aalborg East, Denmark. 2Centre for Health Economics, The University
of York, York, UK. 3MRC Clinical Trials Unit, UCL, London, UK.
Introduction: Protease inhibitors might be sufficient to maintain
complete virological suppression when used as monotherapy for HIV1-positive patients who have achieved sustained virological suppression on combination antiretroviral therapy (ART). The present
study estimated the cost-effectiveness of a strategy of switching
the ART to protease inhibitor monotherapy (PIM) with prompt return
to combination therapy in the event of viral load rebound compared
to continuing the ongoing triple-therapy (OTT) in the long-term
management of HIV-1-positive patients.
Materials and Methods: A within-trial cost-effectiveness analysis and
modelling of lifetime cost-effectiveness was performed based on a
randomized controlled trial of Protease Inhibitor monotherapy Versus
Ongoing Triple-therapy (PIVOT).The setting was HIV outpatient care in the
UK National Health Service, and the trial involved 587 patients, aged 18
years or more, who achieved sustained virological suppression and have a
CD4 cell count 100 cells/mm3. Outcomes were NHS costs (2012 UK
pounds sterling) and quality-adjusted life-years (QALY) with comparative
results presented as incremental cost-effectiveness ratios (ICERs).
Results: Overall, PIM was cost-effective compared to OTT. PIM was
cost-saving due to large savings in the ART drug costs while being
no less effective in terms of QALYs in the within-trial analysis and
only marginally less effective with modelling. In the base-case withintrial analysis, the incremental total cost per patient was £6,424.11
(95% confidence interval: £7,418.84 to £5,429.38) and the incremental QALY was 0.0051 (95% confidence interval: 0.0479 to
0.0582) making PIM dominant compared to OTT. Multiple sensitivity
analyses were conducted to assess the importance of assumptions
surrounding drug costs, missing data, trial protocol driven costs
and mortality. In all sensitivity analyses, PIM was cost-saving and no
Oral Abstracts
marked difference in QALY was observed. Modelling of life time
costs and QALYs showed significant cost-savings and marginally less
effectiveness such that switching to PIM appeared cost-effective at
accepted cost-effectiveness thresholds.
Conclusions: The results suggest that PIM is a cost-effective treatment strategy compared to OTT for HIV-1-positive patients who have
achieved sustained virological suppression.
O22 HEPATITIS C
O221
Hepatitis C, from screening to treatment, a revolution
Karine Lacombe
Infectious and Tropical Diseases Department, Saint-Antoine Hospital,
Paris, France.
Initially associated with blood transfusions and hospital care, the hepatitis
C virus (HCV) epidemic has since moved rapidly onwards to intravenous
drug users, where it poses a major problem still today. Despite numerous
harm reduction programs, such as needle exchange, opiate substitution
and controlled shooting galleries, drug addiction remains the number one
route of HCV transmission around the world. However, in HIV-positive
patients, the HCV epidemic experienced a major shift in the mid-90s, with
sexual transmission among particularly men who have sex with men
(MSM) surfacing as a major route of HCV acquisition. Until recently,
therapeutic options in HCV infection had been quite limited, based largely
on the use of combined Peg-interferon and ribavirin, with disappointing
results in HIV-positive patients. With the recent, exciting developments
in HCV research, new targets on the virus replication cycle have been
discovered. After the release in 2011 of the first direct antiviral agents
inhibiting the NS3/4 antiprotease, the development of drugs with newer
mode of action, more efficient and with higher tolerance profiles has
greatly accelerated. They may greatly change the course of treatment:
once daily, highly active and easily-tolerated regimens, administered for a
short period of time with HCV eradication in more than 90% of patients,
independently of prior treatment, level of fibrosis and comorbidities
such as HIV co-infection. This definitely has the potential to curb the
HCV epidemic towards an HCV cure, provided that advocacy for broadaccess to treatment is successful for those most in need. Their use in
resource-constrained settings may also be the next political challenge
for HCV.
O222
Safety and efficacy of ombitasvir 450/r
and dasabuvir and ribavirin in HCV/HIV-1 co-infected
patients receiving atazanavir or raltegravir ART regimens
Joseph J Eron1; Jay Lalezari2; Jihad Slim3; Joseph Gathe4;
Peter J Ruane5; Chia Wang6; Richard Elion7; Gary Blick8; Amit Khatri9;
Yiran B Hu10; Krystal Gibbons11; Linda Fredrick10; Melannie Co12;
Ronald D’Amico13; Barbara Da Silva-Tillmann14; Roger Trinh15 and
Mark S Sulkowski16
1
Division of Infectious Diseases, University of North Carolina, Chapel
Hill, NC, USA. 2Quest Clinical Research, San Francisco, CA, USA.
3
Infectious Disease Medicine, St. Michael’s Medical Center, Newark,
NJ, USA. 4Infectious Disease, Cure C. Consortium, Houston, TX, USA.
5
Peter J. Ruane, MD, Inc., Infectious Disease, Los Angeles, CA, USA.
6
Infectious Diseases, Virginia Mason Medical Center, Seattle, WA,
USA. 7Clinical Medicine, Whitman-Walker Health, Washington, DC,
USA. 8Infectious Diseases, CIRCLE CARE Center, Norwalk, CT, USA.
9
Oral Abstracts
Efficacy and safety of 12 or 24-week 3D + RBV in HCV/HIV coinfected patients subgrouped by HIV ART regimen
12-week 3D RBV
12-week 3D RBV
24-week 3D RBV
24-week 3D RBV
Parameter, n/N (%)
SVR4
SVR12
Adverse events and laboratory abnormalities
ATV
15/16 (93.8)
15/16 (93.8)
RAL
14/15 (93.3)
14/15 (93.3)
ATV
12/12 (100)
NA
RAL
19/20 (95.0)
NA
Ocular icterus
Jaundice
Total bilirubin
5/16 (31.3)
2/16 (12.5)
0
0
1/12 (8.3)
0
0
0
Grade 3
Grade 4
Aspartate aminotransferase
8/16 (50.0)
1/16 (6.3)
2/15 (13.3)
0
6/12 (50.0)
0
0
0
Grade 3
0
0
0
1/20 (5.0)
Grade 4
0
0
0
0
9
Clinical Pharmacokinetics, AbbVie Inc., North Chicago, IL, USA.
Statistics, AbbVie Inc., North Chicago, IL, USA. 11Clinical Research
Management, AbbVie Inc., North Chicago, IL, USA. 12Medical Review,
AbbVie Inc., North Chicago, IL, USA. 13Medical Affairs, AbbVie Inc.,
North Chicago, IL, USA. 14Medical Safety Evaluation, AbbVie Inc.,
North Chicago, IL, USA. 15Antiviral Global Project Team, AbbVie Inc.,
North Chicago, USA. 16Viral Hepatitis Center, Johns Hopkins
University, Baltimore, MD, USA.
10
Objective: Whether concomitant HIV antiretroviral therapy (ART)
affects the safety and efficacy of interferon-free HCV therapies or
whether HCV treatment may negatively affect HIV control is unclear.
We assessed the 3 direct-acting antiviral (3D) regimen of ombitasvir,
ABT-450 (identified by AbbVie and Enanta; co-dosed with ritonavir)
and dasabuvir with ribavirin (RBV) in HCV/HIV-1 co-infected patients
with and without cirrhosis, including HCV treatment-experienced,
receiving atazanavir (ATV)- or raltegravir (RAL)-based ART therapy.
Methods: HCV genotype 1-positive treatment-naı̈ve or pegIFN/RBVexperienced patients, with or without Child-Pugh A cirrhosis, CD4
count ]200 cells/mm3 or CD4 % ]14%, and plasma HIV-1 RNA
suppressed on stable ART received open-label 3D RBV for 12 or 24
weeks. Rates of HCV-sustained virologic response at post-treatment
weeks 4 and 12 (SVR4 and SVR12, respectively) and bilirubin-related
adverse events (AEs) are reported from post-hoc analyses for
subgroups defined by treatment duration and ART regimen.
Results: The SVR12 rate for patients receiving 12 weeks of 3D RBV
was 93.5% with comparable rates in patients receiving either ATV
(93.8%) or RAL therapy (93.3%) (Table 1). The SVR4 rate for the 24week arm was 96.9% with a single virologic breakthrough at treatment week 16 in a patient receiving RAL therapy. Patients receiving
concomitant ATV had more AEs related to indirect hyperbilirubinemia including ocular icterus, jaundice and grade 3 or 4 elevations in
total bilirubin (predominantly indirect). No patient discontinued the
study due to AEs, and no serious AEs were reported during or after
treatment. No patient had a confirmed plasma HIV-1 RNA value
]200 copies/mL during the treatment period.
Conclusions: In this first study to evaluate an IFN-free regimen in
HCV genotype 1-positive treatment-naı̈ve and experienced patients
with HIV-1 co-infection, including those with cirrhosis, high rates of
SVR were comparable to those with HCV monoinfection. Indirect
hyperbilirubinemia was consistent with the known ABT-450 inhibition of the OATP1B1 bilirubin transporter, RBV-related haemolytic
anaemia and inhibitory effect of ATV on bilirubin conjugation. The
laboratory abnormalities and AEs observed did not negatively affect
treatment response or lead to treatment discontinuation.
O23 WHEN EAST MEETS WEST: ISSUES
FOR HIV CARE ACROSS EUROPE
O231
Drug use, HIV, HCV and TB: major interlinked challenges in
Eastern Europe and Central Asia
Michel Kazatchkine
United Nations Special Envoy for HIV/AIDS in Eastern Europe and
Central Asia, Geneva, Switzerland.
Eastern Europe and Central Asia have the largest drug epidemic
globally and the fastest and still expanding HIV epidemic. The Russian
Federation and Ukraine together account for over 90% of the reported AIDS cases in the region. If small in absolute numbers, the
epidemics are however significant in prevalence rate in most countries
of Central Asia. Most heroin and many of the new synthetic or
home-made drugs are injected, which has led to high prevalence
levels (up to 90%) of HCV infection in people who inject drugs (PWID).
The two epidemics of HIV and HCV are in turn interlinked with TB
and MDR-TB that are highly prevalent among marginalized populations in the region. Despite progress in the last two years, access to
antiretroviral treatment remains far below global levels and increases
more slowly than new reported cases of HIV. Access to prevention is
limited with low coverage of needle exchange programs and very low
or inexistent access to opioid substitutive therapy. There are few
exceptions to this situation, including Ukraine where harm reduction
programs are being scaled up together with significant peer outreach
programs for PWIDs. This is likely to be the reason why the epidemic
curves in the Russian Federation and Ukraine are now diverging. The
region faces many structural, cultural, societal and political obstacles
in responding to these quadruple epidemics. Without a significantly
expanded and strengthened response, these epidemics will remain
major causes of illness and premature deaths in the region.
O232
HIV epidemic in Russia and neighbouring countries
Vadim Pokrovskiy
Russian Federal AIDS Centre, Moscow, Russian Federation.
Reports of HIV/AIDS cases attributed to sexual transmission from
foreigners were published in the USSR in the mid of 80s. In the initial
decade of the epidemic, the subtype B was found in men who have sex
with men (MSM) population and several non-B subtypes were
identified in heterosexual persons. The first case of HIV infection in
10
intravenous drug users (IVDU) was reported in 1993 and since then a
specific subtype A and its recombinants invaded the intravenous drug
users (IVDU) populations of the region with the highest rate in Estonia,
Russia and Ukraine. The concentrated HIV epidemic in IVDUs is still the
main problem in the Eastern Europe; however, the rate of heterosexual
transmission is increasing and many evidences of HIV prevalence rise in
MSM are published. UNAIDS estimations for the number of HIVpositive persons living in the region range from 980,000 to 1,300,000
but distribution of HIV-cases is uneven and the prevalence rate
of HIV infection in separate regions is over 1%. Mass seasonal labour
migration from Central Asia and Caucasian republics to Russia
transmits HIV to these countries. Prevention programs in the region
are limited, and ART coverage is not more than 20% of the total HIVpositive population. The lack of concern about the epidemic, absence
of effective national strategies and limited allocated resources are the
main barriers to prevention and care in many countries. Local conflicts,
rising religiosity and discrimination are adverse factors. The nearterm forecast for the epidemic in the region is pessimistic and further
international advocacy is needed to improve the situation.
O233
Treatment and care of TB across Europe
Ole Kirk
Copenhagen HIV programme, University of Copenhagen,
Copenhagen, Denmark.
There continues to be profound differences in TB incidences as well as in
TB treatment and care across Europe in recent years. High TB incidences
are observed in Eastern Europe and especially among injecting drug users
(IDUs), and there are large overlaps with a HIV epidemic, which is also far
from being under control in this region. Further, mortality rates among
HIV-positive patients with TB in Eastern Europe were in the 2000s 35
fold higher compared with other parts of Europe. As of 2014, there remain
many challenges in the organizational set-up of TB care in Eastern Europe
and often only limited possibilities of support for the vulnerable IDU
populations, including in particular opioid substitution therapy. Further,
Oral Abstracts
high prevalences of multi-drug-resistant TB (MR-TB) are an increasing
problem in Eastern Europe which in several settings reached beyond
50% among patients previously treated for TB. Obviously, this causes
problems for immediate therapy of the individual patients and for
development of secondary resistance during therapy. The panel of TB
drugs available in TB clinics in Eastern Europe is often limited, and a quick
TB diagnosis and acknowledgement of the resistance pattern to guide
initial therapy seems to be a priority. For HIV-positive patients in
particular, better access to cART may also be an important tool to reduce
the TB incidence among these patients. Thus, treatment and care of TB
patients in especially Eastern Europe are facing a variety of diagnostic and
therapeutic challenges in the coming years.
O234
Regional differences in self-reported HIV care and
management in the EuroSIDA study
Kamilla Grønborg Laut1; Amanda Mocroft2; Jeffrey Lazarus1;
Peter Reiss3; Jürgen Rockstroh4; Igor Karpov5; Aza Rakhmanova6;
Brygida Knysz7; Santiago Moreno8; Panagiotis Gargalianos9;
Jens Lundgren1 and Ole Kirk1 on behalf of Eurosida in
Eurocoord
1
Department of Infectious Diseases, Rigshospitalet, University of
Copenhagen, Copenhagen, Denmark. 2Department of Infection and
Population Health, University College London, London, UK.
3
Academic Medical Center, University of Amsterdam and Stichting
HIV Monitoring, Amsterdam, Netherlands. 4Immunologische
Ambulanz, University Hospital Bonn, Bonn, Germany. 5Department of
Infectious Diseases, Belarus State Medical University, Minsk, Belarus.
6
Department of Infectious Diseases, Botkin Hospital St Petersburg,
Russian Federation. 7Department of Infectious Diseases, Wroclaw
University School of Medicine, Wroclaw, Poland. 8Servicio
Enfermedades Infecciosas, Hospital Ramon y Cajal, Madrid, Spain.
9
Infectious Diseases Unit, 1st Internal Medicine Department, G
Gennimatas Hospital, Athens, Greece.
Abstract O234Figure 1. Regional differences in self-reported HIV management: initiation of ART in asymptomatic individuals, viral
resistance testing, and routine screening for selected comorbidities.
Screening for cervical cancer included performing cervical smear and gynaecological exam. Screening for anorectal cancer included performing
anal pap and anorectal exam. § Based on responses from 67/68 non-Eastern European and 12/12 Eastern European clinic. § Based on responses
from 67/68 non-Eastern European and 12/12 Eastern European clinic. * B0.05. **p B0.001.
11
Introduction: EuroSIDA has previously reported a poorer clinical prognosis for HIV-positive individuals in Eastern Europe (EE) as compared
with patients from other parts of Europe, not solely explained by
differences in patient characteristics. We explored regional variability
in self-reported HIV management at individual EuroSIDA clinics, with a
goal of identifying opportunities to reduce the apparent inequalities
in health.
Methods: A survey (www.chip.dk/eurosida/csurvey) on HIV management was conducted in early 2014 in all currently active EuroSIDA
clinics. Responders in EE were compared with clinics in all other
EuroSIDA regions combined (non-EE). Characteristics were compared
between regions using Fishers exact test.
Results: A total of 80/97 clinics responded (82.5%, 12/15 in EE, 68/82
in non-EE). Participating clinics reported seeing a total of 133,532
patients [a median of 1300 per clinic (IQR 7002399)]. The majority
of clinics requested viral load and CD4 measurements at least every
six months for patients on as well as off ART (EE 66.7%, non-EE 75%,
p 0,72). Significantly fewer EE clinics performed resistance tests
before ART as well as upon treatment failure (Figure 1). Half of the EE
clinics indicated following WHO guidelines (EE 50%, non-EE 7.4%,
p B0.0001), whereas most non-EE clinics followed EACS guidelines
(non-EE 76.5%, EE 41.7%, p0.017). The majority of EE clinics and ¼
non-EE clinics indicated deferral of ART initiation in asymptomatic
individuals until CD4 5350 cells/mm3 (Figure 1). There were no
significant regional differences in screening haematology, liver or
renal function, which the majority of clinics reported to do routinely.
However, EE clinics reported screening significantly less for cardio-
Oral Abstracts
vascular disease (CVD), and only about half screened for tobacco use,
alcohol consumption and drug use (Figure 1). Screening for cervical
cancer and for anorectal cancer was low in both regions (Figure 1).
Conclusions: We found significant regional variability in self-reported
HIV management across Europe, with less resistance testing, screening for CVD and substance use in EE. EE clinics indicated deferral of
ART initiation for longer than non-EE clinics. Adherence to international guidelines for cervical cancer screening was poor in both
regions. Whether differences in HIV management are reflected in
clinical outcomes deserves further investigation.
O235
Major challenges in clinical management of TB/HIV
co-infected patients in Eastern Europe compared with
Western Europe and Latin America
Anne Marie Efsen1; Anna Schultze2; Frank Post3;
Alexander Panteleev4; Hansjakob Furrer5; Robert Miller6;
Aliaksandr Skrahin7; Marcelo H Losso8; Javier Toibaro8;
Enrico Girardi9; José Miro10; Mathias Bruyand11; Niels Obel1,2;
Joan Caylá10; Daria Podlekareva1; Jens Lundgren1; Amanda Mocroft2;
Ole Kirk1 and EuroCoord TB/HIV Study Group1
1
Department of Infectious Diseases and Rheumatology, CHIP,
2
Department of Infection and Population Health, University College
Abstract O235Figure 1. Susceptibility of initial TB treatment.
12
London, London, UK. 3Department of Sexual Health, King’s College
Hospital, London, UK. 4City TB Hospital 2, HIV/TB, St. Petersburg,
Russian Federation. 5Department of Infectious Diseases, Bern
University Hospital and University of Bern, Bern, Switzerland. 6Centre
for Sexual Health and HIV Research, University College London,
London, UK. 7Republican Research and Practical Centre for
Pulmonary and TB, Clinical Department, Minsk, Belarus. 8Hospital
Gral. de Agudos JM Ramos Mejı́a, Servicio Inmunocomprometidos,
Buenos Aires, Argentina. 9Istituto Nazionale Malattie Infettive L.
Spallanzani IRCCS, UOC Epidemiologia Clinica, Rome, Italy.
10
Hospital Clinic Universitari de Barcelona, Hospital Clinic
Universitari, Barcelona, Spain. 11Université Bordeaux Segalen,
INSERM U897, Bordeaux, France.
Introduction: Rates of both TB/HIV co-infection and multi-drugresistant (MDR) TB are increasing in Eastern Europe (EE). Data on the
clinical management of TB/HIV co-infected patients are scarce. Our
aim was to study the clinical characteristics of TB/HIV patients in
Europe and Latin America (LA) at TB diagnosis, identify factors associated with MDR-TB and assess the activity of initial TB treatment
regimens given the results of drug-susceptibility tests (DST).
Materials and Methods: We enrolled 1413 TB/HIV patients from 62
clinics in 19 countries in EE, Western Europe (WE), Southern Europe
(SE) and LA from January 2011 to December 2013. Among patients who
completed DST within the first month of TB therapy, we linked initial
TB treatment regimens to the DST results and calculated the distribution of patients receiving 0, 1, 2, 3 and ]4 active drugs in each region.
Risk factors for MDR-TB were identified in logistic regression models.
Results: Significant differences were observed between EE (n844), WE
(n152), SE (n164) and LA (n253) for use of combination
antiretroviral therapy (cART) at TB diagnosis (17%, 40%, 44% and 35%,
pB0.0001), a definite TB diagnosis (culture and/or PCR positive for
Mycobacterium tuberculosis; 47%, 71%, 72% and 40%, pB0.0001) and
MDR-TB prevalence (34%, 3%, 3% and 11%, p B0.0001 among those
with DST results). The history of injecting drug use [adjusted OR
(aOR) 2.03, (95% CI 1.004.09], prior TB treatment (aOR 3.42,
95% CI 1.886.22) and living in EE (aOR 7.19, 95% CI 3.2815.78) were
associated with MDR-TB. For 569 patients with available DST, the initial TB
treatment contained ]3 active drugs in 64% of patients in EE compared
with 9094% of patients in other regions (Figure 1a). Had the patients
received initial therapy with standard therapy [Rifampicin, Isoniazid,
Pyrazinamide, Ethambutol (RHZE)], the corresponding proportions would
have been 64% vs. 8697%, respectively (Figure 1b).
Conclusion: In EE, TB/HIV patients had poorer exposure to cART, less
often a definitive TB diagnosis and more often MDR-TB compared
to other parts of Europe and LA. Initial TB therapy in EE was suboptimal, with less than two-thirds of patients receiving at least three
active drugs, and improved compliance with standard RHZE treatment
does not seem to be the solution. Improved management of TB/HIV
patients requires routine use of DST, initial TB therapy according to
prevailing resistance patterns and more widespread use of cART.
O236
The cascade of HIV care in Russia, 20112013
Anastasia Pokrovskaya; Anna Popova; Natalia Ladnaya and Oleg Yurin
Central Scientific Research Institute of Epidemiology, Russian Federal
AIDS Centre, Moscow, Russian Federation.
Introduction: The cascade of HIV care is one of the main tools to assess
the individual and public health benefits of antiretroviral therapy (ART)
and identify barriers of treatment as prevention (TasP) concept realization.We aimed to characterize the changes in engagement of HIV-positive
persons in care in Russia during three years (20112013).
Methods: We defined seven steps in the cascade of care framework:
HIV infected (estimation data), HIV diagnosed, linked to HIV care, retained
Oral Abstracts
in HIV care, need ART, on ARTand viral suppressed (VL B 1000 copies/mL
during 12 month ART). Information was extracted from the Federal
AIDS Centre database and from the national monitoring forms of
Rospotrebnadzor from the beginning of 2011 to 31 December 2013.
Results: Nearly 668,032 HIV-diagnosed Russian residents were alive
by the end of 2013, which consisted 49% of the estimated 1,363,330
people living with HIV. Among the alive HIV-diagnosed patients,
516,403 (77%) were linked to care and 481,783 (72%) were retained.
Of 163,822 (25% of HIV diagnosed) patients who were eligible for
ART, 156,858 (96%) were on treatment while 127,054 (81%) had viral
suppression. However, only 19% of HIV-diagnosed patients achieved
viral suppression which is necessary to prevent viral transmission.
We noted substantial improvements over time in the proportion of
individuals on ART. The proportion of patients who received ART increased from 24% in 2011 to 34% in 2013. The most significant
leakages of patients during three years were on steps: ‘‘HIV infected
0 HIV diagnosed’’ (loss 55% in 2011, 53% in 2012, and 51% in
2013), ‘‘HIV diagnosed 0 Linked to care’’ (23% yearly) and ‘‘Retained
in care 0 Need ART’’ (76%, 70%, and 66%, respectively).
Conclusion: The stages of HIV diagnosis and estimation of ART
eligibility were the most vulnerable to leakage. Encouraging HIV
testing and earlier ART initiation are needed to maximize the effects
of TasP interventions and to contain the spread of HIV in Russia.
O237
Large disparities in HIV treatment cascades between eight
European and high-income countries analysis of break
points
Alice Raymond1; Andrew Hill2 and Anton Pozniak3
1
Department of Public Health, Imperial College London, London, UK.
2
Molecular and Clinical Pharmacology, Liverpool University,
Liverpool, UK. 3St Stephens Centre, Chelsea and Westminster
Hospital, London, UK.
Introduction: Patients on antiretroviral treatment with undetectable
HIV RNA levels have a significantly lower risk of clinical disease
progression and onward HIV transmission. This study aimed to estimate and compare the percentage of all HIV-positive people who
are diagnosed, are linked to care, are taking antiretroviral treatment and have undetectable HIV RNA, in eight European and highincome countries: the United States, the United Kingdom, France,
the Netherlands, Denmark, Australia, British Columbia (Canada) and
Georgia.
Materials and Methods: For each country, the number of people in
five key stages of the HIV treatment cascade was collected: 1. HIV
infected, 2. Known to be HIV positive, 3. Linked to care, 4. Taking
antiretroviral treatment, and 5. Having undetectable HIV RNA. Estimates
were extracted from national reports [13], the UNAIDS database,
conference proceedings [4] and peer-reviewed articles [57]. The quality
of the estimates and reporting methods were assessed individually
for each country, with selection criteria such as availability of nationwide
database and routinely collected data. Treatment cascades were constructed using estimates from 2010 to 2012.
Results: As shown in Table 1, the percentage of all infected people
with undetectable HIV RNA ranged from 20% in Georgia to 59% in
Denmark. Of the high-income countries, the United States has the
lowest percentage of individuals with undetectable viral load (25% to
median 52%), associated with the highest HIV incidence rate (15.30
per 100,000 to median 6.07 per 100,000). The pattern of the cascades
differed between countries: in the United States, there is a fall from
66% to 33% ( 33%) between linkage to care and start of antiretroviral
treatment. However, in Georgia, the greatest loss in continuum was
zat diagnosis, with 48% of undiagnosed HIV-positive individuals.
13
Oral Abstracts
Abstract O237Table 1. HIV treatment cascades in eight European and high-income countries
Countries
France
Netherlands
United States
United Kingdom
Australia
British Columbia
Denmark
Georgia
Number living with HIV
149,900
25,000
1,148,200
98,400
33,000
11,700
6500
4900
81
82
75
71
85
52
Percentage linked to care
74
73
66
79
67
81
44
Percentage on ART
60
59
33
67
35
51
62
26
52
53
25
58
32
35
59
20
Percentage diagnosed
Percentage with
undetectable HIV RNA
Conclusions: There are great disparities among European and highincome countries in the percentage of HIV-positive individual with undetectable HIV RNA. Furthermore, the treatment cascades show different
key break points, underlying inequalities in HIV care between countries.
References
1. Aghaizu A, Brown AE, Nardone A, Gill ON, Delpech VC &
contributors. HIV in the United Kingdom 2013 Report: data to end
2012. London: Public Health England; 2013.
2. van Sighem A, Gras L, Kesselring A, Smit C, Engelhard E, Stolte I,
et al. HIV Infection in the Netherlands. Amsterdam, The Netherlands:
Stichting HIV Monitoring Report; 2013.
3. Standing Council on Health. The Australian response to HIV and
AIDS. 2012.
4. Supervie V, Costagliola D. The spectrum of engagement in HIV
care in France. 20th Conference on Retroviruses and Opportunistic
Infections; 2013 Mar; Atlanta, USA. Abstract #: 1030.
5. Helleberg M, Häggblom A, Sönnerborg A, Obel N. HIV care in the
Swedish-Danish HIV Cohort 19952010, Closing the Gaps. PLoS ONE.
2013;8(8):e72257.
6. Bohdan N, Montaner JSG, Colley G, Lima VD, Chan K, Heath K,
et al. The cascade of HIV care in British Columbia, Canada, 1996
2011. Lancet Infect Dis. 2014;14(1):409.
7. Hall HI, Frazier EL, Rhodes P, Holtgrave DR, Furlow-Parmley C,
Tang T, et al. Differences in human immunodeficiency virus care and
treatment among subpopulations in the United States. JAMA Int
Med. 2013;173(14):133744.
O31 CO-MORBIDITIES AND
COMPLICATIONS PART I
O311
Management of drug-resistant TB in patients with HIV
co-infection
Graeme Meintjes
Institute of Infectious Diseases and Molecular Med, University of
Cape Town, Cape Town, South Africa.
The World Health Organization estimates that 450,000 cases of
drug-resistant (DR) tuberculosis (TB) occurred worldwide in 2012. In
South Africa, over 15,000 cases were diagnosed. Over half of patients
in South Africa with TB are HIV co-infected. The management of drugresistant TB is complex, prolonged, costly, associated with multiple
toxicities and thus difficult for patients to complete. Disengagement
from follow-up is common. Co-infection with HIV presents a number
of additional challenges in DR TB management including shared
drug toxicities between TB and HIV drugs, potential for increased
drug toxicity due to underlying HIV-related organ disease such as
nephropathy, pharmacokinetic drugdrug interactions and immune
reconstitution inflammatory syndrome including manifestations at
extrapulmonary sites. Mortality with multi-drug-resistant (MDR) TB is
higher in HIV-positive patients. Mortality is similar for HIV-positive
and uninfected patients with extremely drug-resistant (XDR) TB,
given the current lack of effective therapy, with over 70% case
fatality by five years. ART improves survival in patients with DR TB,
and timing of ART initiation in relation to TB treatment should be
similar to patients with drug-susceptible TB. New (e.g. bedaquiline
and delaminid) and repurposed (e.g. linezolid and clofazamine) drugs
promise to improve the prognosis of patients with DR TB. Several
clinical trials of new regimens are ongoing and planned, and early
data from the Bedaquiline Clinical Access Programme in South Africa
suggests much improved short-term outcomes when bedaquiline
/ linezolid and/or clofazamine are included in the regimen of
patients with XDR and pre-XDR TB including patients with HIV coinfection. There are important considerations with respect to QT
prolongation and ART drug interactions related to bedaquiline that
need to be factored in treatment decisions and monitoring plans.
O312
CD4 cell count and the risk of infective and non-infective
serious non-AIDS events in HIV-positive persons seen for
care in Italy
Giordano Madeddu1; Antonella D’Arminio Monforte2; Enrico Girardi3;
Antonio Di Biagio4; Sergio Lo Caputo5; Roberta Piolini6;
Giulia Marchetti2; Giampietro Pellizzer7; Andrea Giacometti8;
Laura Galli9; Andrea Antinori10 and Alessandro Cozzi Lepri11
on behalf of the ICONA Foundation Study12
1
Unit of Infectious Diseases, University of Sassari, Sassari, Italy.
2
Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy.
3
Clinical Epidemiology, National Institute for Infectious Diseases,
Rome, Italy. 4Infectious Diseases, IRCCS San Martino Hospital, Genoa,
Italy. 5Infectious Diseases, Santa Maria Annunziata Hospital, Florence,
Italy. 6Infectious Diseases, Luigi Sacco Hospital, University of Milan,
Milan, Italy. 7Infectious Diseases, Vicenza Hospital, Vicenza, Italy.
8
Infectious Diseases, Ancona Hospital, Ancona, Italy. 9Infectious
Diseases, San Raffaele Hospital, Milan, Italy. 10Clinical Department,
National Institute for Infectious Diseases ‘‘L. Spallanzani’’, Rome,
Italy. 11Infection and Population Health, University College London,
London, UK. 12Health Sciences, University of Milan, Milan, Italy.
Introduction: Serious non-AIDS events (SNAE) are frequent in HIV
patients receiving cART. Current CD4 count was shown to be more
strongly associated with infective compared to not-infective SNAE and
unable to predict cardiovascular events. We investigated the relationship
between baseline and current CD4 count and the risk of both infective and
non-infective SNAE in HIV-positive patients according to current ART use.
Methods: We included all HIV-positive persons enrolled in the ICONA
Foundation Study cohort who had at least one follow-up visit. SNAE
were grouped in infective (pneumonia, sepsis, endocarditis and
meningitis) and non-infective (malignancies, chronic kidney disease,
14
Oral Abstracts
Abstract O312Table 1. Adjusted rate ratios (ARR) of infective and non-infective serious non-AIDS events (SNAE) from fitting Poisson
regression models
Infective SNAE
Non-infective SNAE
ART naive
Currently off ART
Currently on ART
ART naive
Currently off ART
Currently on ART
ARR (95% CI),
ARR (95% CI),
ARR (95% CI),
ARR (95% CI),
ARR (95% CI),
ARR (95% CI),
p value
p value
p value
p value
p value
p value
Current CD4 count
(cells/mmc)
1.00
1.00
1.00
1.00
1.00
1.00
201350
0.19 (0.10, 0.34),
1.00 (0.28, 3.55),
0.35 (0.23, 0.52),
0.40 (0.20, 0.81),
0.90 (0.33, 2.47),
0.48 (0.32, 0.72),
B0.001
0.996
B0.001
0.011
0.832
B0.001
351500
0.11 (0.06, 0.20),
0.38 (0.08, 1.83),
0.24 (0.16, 0.37),
0.18 (0.09, 0.36),
0.55 (0.19, 1.56),
0.56 (0.37, 0.84),
B0.001
0.226
B0.001
B0.001
0.258
0.005
501750
0.08 (0.04, 0.16),
0.10 (0.01, 0.86),
0.21 (0.13, 0.32),
0.19 (0.10, 0.35),
0.26 (0.07, 0.93),
0.47 (0.33, 0.71),
750
B0.001
0.11 (0.05, 0.22),
0.036
0.20 (0.01, 2.06),
B0.001
0.14 (0.08, 0.26),
B0.001
0.16 (0.07, 0.35),
0.027
0.41 (0.11, 1.50),
B0.001
0.32 (0.20, 0.52),
B0.001
0.177
B0.001
B0.001
0.176
B0.001
5200
Baseline CD4 count
(cells/mmc)
1.00
1.00
1.00
1.00
1.00
1.00
201350
0.12 (0.05, 0.27),
0.13 (0.02, 1.04),
0.59 (0.39, 0.88),
0.34 (0.15, 0.79),
0.78 (0.29, 2.09),
1.27 (0.91, 1.76),
B0.001
0.055
0.010
0.012
0.625
0.154
351500
0.10 (0.05, 0.19),
B0.001
0.20 (0.05, 0.75),
0.017
0.53 (0.35, 0.80),
0.003
0.15 (0.07, 0.33),
B0.001
0.32 (0.12, 0.90),
0.031
0.89 (0.62, 1.27),
0.523
501750
0.09 (0.05, 0.16),
0.07 (0.01, 0.58),
0.49 (0.31, 0.76),
0.16 (0.08, 0.32),
0.36 (0.13, 1.01),
1.09 (0.76, 1.56),
B0.001
0.014
0.002
B0.001
0.052
0.643
0.07 (0.03, 0.14),
0.44 (0.09, 2.08),
0.49 (0.24, 1.02),
0.21 (0.10, 0.42),
0.29 (0.07, 1.20),
0.72 (0.38, 1.34),
B0.001
0.302
0.055
B0.001
0.087
0.298
5200
750
cardiovascular events, hepatic events and pancreatitis) aetiology.
Incidence of these event groups were calculated overall and according
to baseline and current CD4 count (grouped as 0200, 201350, 351
500, 501750, and 750 cells/mm3). Participants’ follow-up accrued
from the date of enrolment (baseline) to a diagnosis of SNAE or their
last visit. An event was defined the first time one of the considered
SNAE occurred so that each person contributed a single event. A
Poisson regression model for each of the two endpoints was used.
Results: A total of 10,822 patients were included (25.3% females,
38.2% heterosexuals) and 26.6% had hepatitis co-infections. Median
age was 36 (IQR 3142) years. Overall, 423 not-infective and 385
infective SNAE were included. The most frequent non-infective
SNAE were malignancies (n 202) and the most frequent infective
SNAE were pneumonia (n 289). Crude rates of non-infective SNAE
were 0.78, 1.08 and 0.80/100 PYFU, and those of infective SNAE were
1.00, 0.51 and 0.66/100 PYFU in ART naive, currently off and currently
on ART patients, respectively. Higher current CD4 count was
associated with reduced risk of both infective and non-infective SNAE
in naives and in patients on ART (Table 1). The association was less
strong in the group which suspended ART (for non-infective SNAE the
p value for interaction between current log-CD4 and ART-status,
p 0.004). Conversely, we found no association between baseline
CD4 count and risk of non-infective SNAE in people treated with ART
(p value for interaction 0.0001). When CVD were considered
separately, there was no association with CD4 count (not shown).
Conclusions: Our findings show that, differently from ART naive,
in ART-treated patients, non-infective SNAE are predicted by current
but not by baseline CD4, suggesting that immune restoration is
crucial to prevent these events.
O313
Predictive value of prostate-specific antigen for prostate
cancer: a nested case-control study in EuroSIDA
Leah Shepherd1; Álvaro Humberto Borges2; Lene Ravn3;
Richard Harvey4; Jean-Paul Viard5; Mark Bower6;
Andrew Grulich7; Michael Silverberg8; Stephane De Wit9;
Ole Kirk2; Jens Lundgren2 and Amanda Mocroft1 on behalf of
EuroSIDA in Eurocoord2
1
London, London, UK. 2Centre for Health & Infectious Diseases
Research, Rigshospitalet, University of Copenhagen, Copenhagen,
Denmark. 3Department of Clinical Biochemistry, Rigshospitalet,
Copenhagen, Denmark. 4Charing Cross Oncology Laboratory and
Trophoblast, Charing Cross Hospital Campus of Imperial College
Healthcare National Health Service Trust, London, UK. 5Centre de
Diagnostic et de Thérapeutique, Université Paris Descartes, Hôtel-D,
Paris, France. 6National Centre for HIV Malignancy, Chelsea and
Westminster Hospital NHS Foundation Trust, London, UK. 7Kirby
Institute, The University of New South Wales, Sydney, Australia.
8
Division of Research, Kaiser Permanente Northern California,
Oakland, USA. 9Department of Infectious Diseases, Saint-Pierre
Hospital, Brussels, Belgium.
15
Oral Abstracts
Abstract O313Figure 1. Total PSA (tPSA) and free PSA (fPSA) levels by time before diagnosis (or last sample date in controls) with
superimposed loess curves. tPSA and fPSA levels were increasing by 13.7 (10.3, 17.3)% and 7.9 (4.7, 11.2)% per year since baseline in cases
(both pB0.01) and were stable in controls (p0.67 and 0.36). Figure includes multiple measurements per man.
Introduction: Although prostate cancer (PCa) incidence is lower
in HIV men than in HIV men, the usefulness of prostate-specific
antigen (PSA) screening in this population is not well defined and
may have higher false negative rates than in HIV men. We aimed
to describe the kinetics and predictive value of PSA in HIV men.
Methods: Men with PCa (n 21) and up to two matched controls
(n 40) with prospectively stored plasma samples before PCa (or
matched date in controls) were selected. Cases and controls were
matched on date of first and last sample, age, region of residence and
CD4 count at first sample date. Total PSA (tPSA), free PSA (fPSA),
testosterone and sex hormone binding globulin (SHBG) were measured. Conditional logistic regression models investigated associations
between markers and PCa. Sensitivity and specificity of using tPSA 4
mg/L to predict PCa was calculated. Mixed models were used to
describe kinetics.
Results: Sixty-one men were included with a median six (IQR 29)
years follow-up. Time between last sample and PCa was seven (411)
months. Cases and controls were well matched at first sample, with a
median age of 51 (IQR 4857) and CD4 of 437 (243610) cells/mm3.
Median tPSA [2.8 (IQR: 1.64.6) and 0.8 (0.51.2) mg/L] and fPSA [0.4
(0.20.8) and 0.3 (0.20.4) mg/L] levels were higher in cases than
controls at first sample. Both tPSA and fPSA increased significantly
over time in cases (Figure 1), to a median at last sample of 6.1 (4.7
9.5) and 0.9 (0.61.3) mg/L, respectively, but were stable in controls,
with a median at last sample of 0.8 (0.51.4) and 0.2 (0.20.4) mg/L
(Figure). Higher levels of tPSA and fPSA were associated with higher
odds of PCa at first sample [OR for 2-fold higher 4.7 (CI: 1.712.9) and
5.4 (1.717.4)]. Elevated tPSA values in cases were detectable ]5
years before PCa (p B0.01). Testosterone [overall median 19.4 (IQR
15.323.9) nmol/L at first sample) and SHBG [50.0 (34.066.0) nmol/L]
levels were similar in cases and controls at first and last sample (all
p 0.7). The most informative predictor of PCa was tPSA (AUC 0.9),
followed by fPSA (0.8). Testosterone (AUC 0.5) and SHBG (0.5)
were poor predictors of PCa. Overall, tPSA level 4 mg/L had 99%
specificity and 37% sensitivity. Performance was best in the year prior
to PCa (specificity: 99%, sensitivity: 88%).
Conclusions: PSA was highly predictive of PCa in HIV men. Our
results indicate that PSA screening in HIV men may be useful, and
further work is needed to identify potentially age-related cut-offs
to maximize sensitivity and specificity to identify those for further
evaluation at early stages of PCa.
O314
Effects of age on symptom burden, mental health and
quality of life amongst people with HIV in the UK
Jennifer McGowan1; Lorraine Sherr1; Alison Rodger1; Martin Fisher2;
Alec Miners3; Margaret Johnson4; Jonathan Elford5; Simon Collins6;
Graham Hart7; Andrew Phillips1; Andrew Speakman1 and
Fiona Lampe1
1
Infection and Population Health, University College London, London,
UK. 2HIV Medicine, Brighton and Sussex University Hospitals NHS
Trust, Brighton, UK. 3Department of Health Services Research and
Policy, London School of Hygiene and Tropical Medicine, London, UK.
4
HIV Medicine, The Royal Free Centre for HIV Medicine, London, UK.
5
Evidence-based Health Care, City University, London, UK. 6HIV
i-Base, London, UK. 7Population Health Sciences, University College
London, London, UK.
16
Oral Abstracts
Abstract O314Table 1. Adjusted association of age with symptom prevalence among PWH
Physical
N3258
symptom distress
Age (years)
%
Health-related
Depression
Adjusted OR*
%
Anxiety
Adjusted OR*
(95% CI)
%
(95% CI)
QoL problem
Adjusted OR*
%
Adjusted OR*
(95% CI)
(95% CI)
B30
60
1.6 (1.1, 2.5)
35
3.1 (1.9, 5.1)
28
3.5 (2.0, 6.1)
63
0.9 (0.6, 1.5)
3039
51
1.1 (0.8, 1.5)
25
1.8 (1.2, 2.7)
19
2.0 (1.2, 3.2)
57
0.7 (0.5, 1.0)
4049
56
1.1 (0.8, 1.5)
31
2.1 (1.5, 3.1)
23
2.3 (1.5, 3.6)
65
0.8 (0.6, 1.2)
5059
]60
61
53
1.3 (1.0, 1.9)
1 (reference)
31
18
2.1 (1.4, 3.1)
1 (reference)
23
12
2.3 (1.4, 3.6)
1 (reference)
72
70
1.1 (0.8, 1.5)
1 (reference)
p0.92 for
p 0.010 for
p0.012 for
p0.004 for
trend
trend
trend
trend
*Odds ratio adjusted for gender/sexuality (MSM, heterosexual men and women) and time with diagnosed HIV (02, 210 and 10 years) using
logistic regression
Introduction: The evolving HIV epidemic, coupled with advances in
HIV treatment, has resulted in an ageing HIV-diagnosed population. It
has been suggested that adverse physical and psychological effects of
HIV may be higher among older people. However, few studies have
examined the effect of older age on well-being for people with HIV.
Materials and Methods: The ASTRA study included 3258 HIVdiagnosed individuals (2248 MSM; 373 heterosexual men; 637 women)
recruited from eight UK clinics in 201112 (64% response rate).
Participants completed a questionnaire that included standard inventories on symptoms and health-related quality of life (HrQoL). Associations of age group with: physical symptom distress (reporting
significant distress for ]1 of 26 symptoms), depression and anxiety
(score ]10 on PHQ-9 and GAD-7, respectively) and HrQoL problem
(reporting problems on ]1 of 5 Eurqol-5D domains) were assessed;
adjustment was made for gender/sexuality and time with diagnosed
HIV.
Results: Of all participants, 87% were taking ART, 76% had VL 550c/
mL and 19% had CD4 B350/mm3. Mean age was 45 years (range 18
88) with 5% B30, 23% 3039, 43% 4049, 22% 5059 and 7% ]60
years. The most prevalent distressing physical symptoms were: lack of
energy/tiredness (26%), difficulty sleeping (24%), muscle-ache/joint
pain (21%) and pain (18%). With older age, there was no clear trend in
prevalence of physical symptom distress, but prevalence of depression
and anxiety decreased, while prevalence of HrQoL problems increased.
This pattern remained after adjustment for gender/sexuality and time
diagnosed with HIV. The increase with age in overall prevalence of
HrQoL problem was due to increased problems for ‘‘mobility,’’ ‘‘selfcare’’ and ‘‘performing usual activities’’ domains, not an increase in
‘‘depression/anxiety.’’ Longer time with diagnosed HIV was strongly
associated with higher prevalence of all symptoms measures and
HrQoL problem (p B0.001 for trend, adjusted models).
Conclusions: Physical and psychological symptoms are common
among people living with HIV, but the burden of these symptoms
is not highest among the older age group. While HrQoL tended to
worsen with older age, physical symptom distress did not, and
mental health improved. This may reflect greater resilience in older
adults, or the potential for ‘‘successful ageing’’: maintaining mental
health despite age-related health losses.
O315
Lack of association between use of efavirenz and death
from suicide: evidence from the D:A:D study
Colette Smith1; Lene Ryom2; Antonella d’Arminio Monforte3;
Peter Reiss4; Amanda Mocroft1; Wafaa El-Sadr5; Rainer Weber6;
Matthew Law7; Caroline Sabin1 and Jens Lundgren2
1
UK. 2CHIP, University of Copenhagen, Copenhagen, Denmark. 3Health
Sciences, San Paolo University Hospital, Milan, Italy. 4Academic
Medical Center, University of Amsterdam and Stichting HIV
Monitoring, Amsterdam, Netherlands. 5Mailman School of Public
Health, Columbia University, New York, USA. 6Division of Infectious
Diseases, University Hospital Zurich, Zurich, Switzerland. 7Kirby
Institute, University of New South Wales, Sydney, Australia.
Introduction: A recent meta-analysis of 4 RCTs showed an increased
rate of suicidality events (suicidal ideation or attempted/completed
suicide) associated with efavirenz (EFV) compared to other regimens,
but only a trend towards a higher rate of completed/attempted
suicides, as only 17 events occurred. We investigated the association
between EFV use and completed suicide.
Materials and Methods: All D:A:D participants were followed from
study entry to the first of death, last study visit or 1 February 2013.
Deaths are centrally validated using cause of death methodology,
which assigns underlying, immediate and up to four contributing
causes of death. Two endpoints were considered: 1) suicide or psychiatric disease as the underlying cause, and 2) suicide or psychiatric
disease mentioned as an underlying, immediate or contributing
cause of death (anywhere). Adjusted rate ratios were calculated
using Poisson regression.
Results: A total of 4420 deaths occurred in 49,717 people over
371,333 person-years (PY) (rate 11.9 per 1000 PY; 95% CI 11.612.3).
A total of 193 deaths (rate 0.52; 0.450.59) had an underlying cause
of suicide or psychiatric disease, and 482 deaths (1.30; 1.181.41)
had suicide or psychiatric disease mentioned anywhere. A strong
association with current CD4 count was seen: for suicide or psychiatric disease mentioned anywhere, rates were: 3.18 (2.553.80) for
B200 cells/uL, 1.60 (1.291.90) for 201350 cells/uL, 1.07 (0.86
1.29) for 351500 cells/uL, 0.95 (0.801.09) for 500 cells/uL and
1.30 (1.181.41) for unknown. Highest rate of suicide or psychiatric
deaths were seen in ART-experienced people currently off ART,
but no differences were seen according to current ART regimen,
which remained after adjustment (Table 1). Consistent results were
obtained when considering additional endpoints of suicide alone as
the underlying cause and death from suicide or any possibly related
cause (psychiatric disease, drug overdose, alcohol related, accidental
or violent), as well as considering recent EFV use in the previous
3 and 6 months.
17
Oral Abstracts
Abstract O315Table 1. Rates of death from suicide, according to current ART use
Rate per
Number/person-years
1000 person-years
(95% CI)
193/371,333
0.52 (0.450.59)
Adjusted RR
(95% CI)
p
B0.0001
Suicide or psychiatric disease as underlying
cause of death
Total
EFV-containing
24/78,580
0.31 (0.810.43)
0.59 (0.331.06)
Other NNRTI-containing
Other ART
31/64,288
66/157,664
0.48 (0.310.65)
0.42 (0.320.52)
0.93 (0.531.62)
0.81 (0.491.32)
No ARTnaı̈ve
21/40,454
0.52 (0.300.74)
1.00
No ARTexperienced
51/30,348
1.68 (1.222.14)
3.24 (1.955.38)
482/371,333
1.30 (1.181.41)
Suicide of psychiatric disease, mentioned as underlying,
immediate of contributing cause of death
Total
EFV-containing
60/78,580
0.76 (0.570.96)
0.42 (0.280.63)
72/64,288
162/157,664
1.12 (0.861.38)
1.03 (0.871.19)
0.68 (0.461.00)
0.52 (0.370.73)
No ARTnaı̈ve
62/40,454
1.53 (1.151.91)
1.00
No ARTexperienced
126/30,348
4.15 (3.434.88)
2.29 (1.633.21)
Other NNRTI-containing
Other ART
Conclusions: The finding of no higher death rates from suicide
amongst those receiving EFV is reassuring. However, there is likely
confounding by indication in our observational study. In light of
conflicting results from RCTs, this potentially could suggest that in
clinical practice EFV may be less frequently prescribed in those with
underlying psychiatric conditions.
O32 CO-MORBIDITIES AND
COMPLICATIONS PART II
O321
Adverse events: ART and the kidney: alterations in renal
function and renal toxicity
Frank Post
Department of HIV/GU Medicine, King’s College London, London, UK.
Renal dysfunction is common in HIV-positive patients who receive
antiretroviral therapy (ART). Several antiretrovirals have been associated with kidney disease progression, inhibition of renal tubular
transporters that mediate creatinine secretion or impaired reabsorption of phosphate and low-molecular weight proteins. These
aberrations of renal function are typically non-treatment limiting
and of unclear clinical significance. By contrast, severe renal toxicity
is infrequent in well-managed patents. Tenofovir-DF and atazanavir
may cause acute tubular injury, tubule-interstitial nephritis or
nephrolithiasis. Discontinuation of the offending drug is required
to mitigate the adverse effects on kidney or bone. This presentation will discuss ART-associated changes in renal function and
treatment-limiting renal toxicity in terms of incidence, risk factors,
putative mechanism and provide recommendations for clinical
practice.
B0.0001
O322
A clinically useful risk-score for chronic kidney disease in
HIV infection
Amanda Mocroft1; Jens Lundgren2; Michael Ross3; Matthew Law4;
Peter Reiss5; Ole Kirk2; Colette Smith1; Debbie Wentworth6;
Jacquie Heuhaus6; Christophe Fux7; Olivier Moranne8;
Phillipe Morlat9; Margaret Johnson10 and Lene Ryom2 on behalf of
the Data on Adverse Events (D:A:D) study group, the Royal Free
Hospital Clinic Cohort and the INSIGHT study group
1
London, London, UK. 2Copenhagen HIV Programme, Department of
Infectious Diseases, Rigshospitalet, University of Copenhagen,
Copenhagen, Denmark. 3Division of Nephrology, Mount Sinai School
of Medicine, New York, USA. 4The Kirby Institute for Infection and
Immunity, University of New South Wales, Sydney, Australia. 5Division
of Infectious Diseases, Department of Global Health, Academic
Medical Centre, University of Amsterdam, Amsterdam, Netherlands.
6
Division of Biostatistics, University of Minnesota, Minnesota, USA.
7
Clinic for Infectious Diseases and Hospital Hygiene, Kantonsspital
Aarau, Aarau, Switzerland. 8INSERM U 897, CHU de Bordeaux,
Université Bordeaux Segalen, Bordeaux, France. 9Department of
Nephrology, Public Health Department, CHU Nice, Nice, France.
10
Thoracic Medicine, Royal Free Hospital NHS Trust, London, UK.
Introduction: Development of a simple, widely applicable risk score
for chronic kidney disease (CKD) allows comparisons of risks or
benefits of starting potentially nephrotoxic antiretrovirals (ARVs) as
part of a treatment regimen.
Materials and Methods: A total of 18,055 HIV-positive persons
from the Data on Adverse Drugs (D:A:D) study with 3 estimated
glomerular filtration rates (eGFRs) 1/1/2004 were included. Persons
with use of tenofovir (TDF), atazanavir (ritonavir boosted (ATV/r) and
unboosted (ATV)), lopinavir (LPV/r) and other boosted protease
inhibitors (bPIs) before baseline (first eGFR 60 ml/min/1.73m2
after 1/1/2004) were excluded. CKD was defined as confirmed (3
months apart) eGFR B60. Poisson regression was used to develop
a score predicting low ( B0 points), medium (14 points) and high
18
Oral Abstracts
disease predicted CKD and were included in the risk score (Figure 1).
The incidence of CKD in those at low, medium and high risk was 0.8/
1000 PYFU (95% CI 0.61.0), 5.6 (95% CI 4.56.7) and 37.4 (95% CI
34.040.7) (Figure 1). The risk score showed good discrimination
(Harrell’s c statistic 0.92, 95% CI 0.900.93). The number needed to
harm (NNTH) in patients starting ATV or LPV/r was 1395, 142 or 20,
respectively, among those with low, medium or high risk. NNTH were
603, 61 and 9 for those with a low, medium or high risk starting
TDF, ATV/r or bPIs. The risk score was externally validated on 2603
persons from the Royal Free Hospital clinic cohort (94 events, incidence 5.1/1000 PYFU; 95% CI 4.16.1) and 2013 persons from the
control arms of SMART/ESPRIT (32 events, incidence 3.8/1000 PYFU;
95% CI 2.55.1). External validation showed consistent CKD rates
across risk groups (Figure 2).
Interpretation: Traditional and HIV-related risk factors were predictive of CKD; all are routinely available, making the risk score easy
to incorporate into clinical practise and of direct relevance for clinical
decision making. NNTH in persons starting potentially nephrotoxic
ARVs at high risk of CKD were low, and alternative ARVs may be more
appropriate.
O323
Abstract O322Figure 1.
D:A:D risk-score for CKD.
( 5 points) risk of developing CKD. Increased incidence of CKD
associated with starting ARVs was modelled by including ARVs as
time-updated variables. The risk score was externally validated on
two independent cohorts.
Results: A total of 641 persons developed CKD during 103,278.5
PYFU (incidence 6.2/1000 PYFU, 95% CI 5.76.7). Older age, intravenous drug use, HCV antibody status, lower baseline eGFR, female
gender, lower CD4 nadir, hypertension, diabetes and cardiovascular
Abstract O322Figure 2. Incidence of CKD in D:A:D, the Royal Free
Hospital Cohort and INSIGHT according to low, medium and high risk
of CKD.
Cardiovascular risk evaluation of HIV-positive patients in
a case-control study: comparison of the D:A:D and
Framingham equations
Samuel Markowicz; Marc Delforge; Coca Necsoi and Stéphane De Wit
Infectious Diseases, CHU Saint-Pierre, Brussels, Belgium.
Introduction: Patients with HIV infection are at increased risk of
developing cardiovascular disease (CVD) due to complex interactions
between traditional CVD risk factors, antiretroviral therapy (ART) and
HIV infection itself [1]. Prevention of CVD is essential as it remains
the most common serious non-AIDS event and contributes significantly to all-cause mortality. A cardiovascular risk-assessment model
tailored to HIV population is thus essential.
Material and Methods: We conducted a retrospective case-control
study within the HIV cohort of the Saint-Pierre Hospital, Brussels. Cases
(n 73) presented a first CVD (ischemic heart disease or stroke)
between January 2002 and December 2012. Controls (n 142) were
patients without any CVD and were matched for age, race, sex and
follow-up duration. We used Wilcoxon test to identify predictors of
cardiovascular risk among the data collected. We compared Framingham [2] and DAD (Data Collection on Adverse Events of anti-HIV
drugs) [3] equations calculated in all patients at time of event,
two, four and six years before. We then simulated the impact on the
DAD scores if different therapeutic interventions had been introduced when patient cardiovascular risk at ten years exceeded
20%.
Results: Comparison of cases and controls showed that C-reactive
protein (CRP) 3 mg/L (p 0.008) and HIV viral load 50 copies/
ml (p 0.007) at time of event, as well as slower increase in CD4 cell
count (p 0.035), were significantly more frequent in cases. DAD
and Framingham median scores in cases and controls are shown
in Figure 1 and Table 1. Smoking cessation lowered the DAD score of
cases at time of event from 21.6% to 18.3%, modification of ART
(discontinuation of indinavir, lopinavir and abacavir) lowered it from
21.6% to 17%, while both interventions with control of blood
pressure and cholesterol lowered it from 21.6% to 12.4%.
Conclusions: Increased CRP levels, uncontrolled HIV viral load at
time of event and slower immunologic response were found to be
associated with increased CVD risk. DAD score in cases increased
more and faster over time than the Framingham score and seems
therefore to be more accurate in identifying HIV-positive patients at
19
Oral Abstracts
Abstract O323Figure 1. Ten-year predicted cardiovascular risk over time according to Framingham (FRA) and DAD equations in cases and
controls.
Abstract O323Table 1. Framingham (FRA) and DAD scores at
time of event, two, four and six years before, in cases and controls
DAD
DAD
FRA
FRA
Year before event cases (%) controls (%) cases (%) controls (%)
6
10.4
10.1
8.3
7.3
4
12.2
11.5
10.7
8.2
2
17
13.2
11.5
9.4
0
21.6
13.5
15.4
10.7
high risk of CVD. Different therapeutic interventions could have led
to a significant reduction of the DAD score in these patients and
should remain a priority in patient management.
References
1. Triant V. HIV infection and coronary heart disease: an intersection
of epidemics. J Infect Dis. 2012;205(Suppl 3):S35561.
2. Anderson KM, Odell PM, Wilson PW, Kannel WB. Cardiovascular
disease risk profiles. Am Heart J. 1991;121:2938.
3. Friis-Möller N, Thiébaut R, Reiss P, Weber R, Monforte AD, De Wit
S, et al. Predicting the risk of cardiovascular disease in HIV-infected
patient: the DAD study. Eur J Cardiovasc Prev Rehab. 2010;17:
491501.
O324
Gender differences in HIV-positive persons in use of
cardiovascular disease-related interventions: D:A:D study
Camilla Ingrid Hatleberg1; Lene Ryom1; Wafaa El-Sadr2;
Amanda Mocroft3; Peter Reiss4; Stephan de Wit5; Francois Dabis6;
Christian Pradier7; Antonella d’Arminio Monforte8;
Martin Rickenbach9; Matthew Law10; Jens Lundgren1 and
Caroline Sabin3
1
CHIP Department of Infectious Diseases, Rigshospitalet, University
of Copenhagen, Copenhagen, Denmark. 2Mailman School of Public
Health, Columbia University, New York, USA. 3Research Department
of Infection and Population Health, University College London,
London, UK. 4Amsterdam Medical Center, University of Amsterdam,
Stichting HIV Monitoring, Amsterdam, Netherlands. 5CHU SaintPierre Hospital, Saint-Pierre Cohort, Brussels, Belgium. 6ISPED, Centre
Inserm U897, University of Bordeaux, Bordeaux, France.
7
Department of Public Health, Nice University Hospital, Nice, France.
8
Department of Health Sciences, San Paolo University Hospital,
Infectious Diseases Unit, Milan, Italy. 9Institute of Social and
Preventive Medicine, University of Lausanne, Swiss Cohort Study,
Lausanne, Switzerland. 10The Kirby Institute, University of New South
Wales, Sydney, Australia.
Introduction: There is a lack of data on potential gender differences
in the use of interventions to prevent and treat cardiovascular
disease (CVD) in HIV-positive individuals. We investigated whether
such differences exist in the D:A:D study.
Material and Methods: Follow-up was from 01/02/99 until the
earliest of death, 6 months after last visit or 01/02/13. Rates of
initiation of lipid-lowering drugs (LLDs), angiotensin-converting enzyme inhibitors (ACEIs), anti-hypertensives and receipt of invasive
cardiovascular procedures (ICPs; bypass, angioplasty, endarterectomy) were calculated in those without a myocardial infarction (MI) or
stroke at baseline, overall and in groups known to be at higher CVD
risk: (i) age 50, (ii) total cholesterol 6.2 mmol/l, (iii) triglyceride
2.3 mmol/l, (iv) hypertension, (v) previous MI, (vi) diabetes, or (vii)
predicted 10-year CVD risk 10%. Poisson regression was used to
assess whether rates of initiation were higher in men than women,
after adjustment for these factors.
Results: At enrolment, women (n 13,039; median (interquartile
range) 34 (2940) years) were younger than men (n 36,664, 39
(3346) years, p 0.001), and were less likely to be current smokers
(29% vs. 39%, p 0.0001), to have diabetes (2% vs. 3%, p0.0001) or
to have hypertension (7% vs. 11%, p0.0001). Of 49,071 individuals
without a MI/stroke at enrolment, 0.6% women vs. 2.1% men
experienced a MI while 0.8% vs. 1.3% experienced a stroke. Overall,
women received ICPs at a rate of 0.07/100 person-years (PYRS)
compared to 0.29/100 PYRS in men. Similarly, the rates of initiation of
LLDs (1.28 vs. 2.46), anti-hypertensives (1.11 vs. 1.38) and ACEIs (0.82
vs. 1.37) were all significantly lower in women than men (Table 1).
20
Oral Abstracts
Abstract O324Table 1. Relative rate (RR) of receipt of each of the four interventions in women versus men, before and after
adjustment for potential confounders (age, year, BMI, high cholesterol, high triglycerides, hypertension, previous MI, diabetes and
moderate/high predicted 10-year Framingham CVD risk score)
Before adjustment
After adjustment
Intervention
RR (95% CI); p-value
RR (95% CI); p-value
Lipid-lowering drugs
0.52 (0.49, 0.56); p0.0001
0.80 (0.75, 0.86); p 0.0001
ACE inhibitors
0.60 (0.56, 0.65); p0.0001
0.80 (0.74, 0.87); p 0.0001
Anti-hypertensives
0.81 (0.75, 0.86); p0.0001
1.16 (1.07, 1.25); p 0.0001
ICPs
0.25 (0.20, 0.32); p0.0001
0.49 (0.38, 0.63); p 0.0001
As expected, initiation rates of each intervention were higher in
the groups determined to be at moderate/high CVD risk; however,
within each high-risk group, initiation rates of most interventions
(with the exception of anti-hypertensives) were generally lower in
women than men. These gender differences persisted after adjustment for potential confounders (Table 1).
Conclusion: Use of most CVD interventions was lower among women
than men in the D:A:D study. Our findings suggest that actions
should be taken to ensure that both men and women are monitored
for CVD and, if eligible, receive appropriate CVD interventions.
O33 RESISTANCE AND TROPISM
O331
Resistance: what is new and on the horizon, and a time to
teach old dogs new tricks?
Jonathan Schapiro
HIV/AIDS clinic, National Haemophilia Center, Tel Aviv, Israel
Understanding HIV drug resistance has played a key role in the success of antiretroviral therapy. This knowledge allowed for the prediction of resistance evolution when a specific drug or combinations
of drugs were administered, informing strategies implemented for
initial and subsequent drug regimens. Resistance testing of individual
patients detects transmitted as well as acquired drug resistance as
a result of treatment failure, leading to improved treatment choices
in drug naı̈ve and drug experienced patients accordingly. The last
two decades has seen a great deal of evolution, improvement and
change in the care of HIV-positive individuals. Much of this was
aimed at preventing, reducing or minimizing the impact of HIV drug
resistance. Drugs with much improved resistance characteristics were
designed and gained widespread use, as well as those with superior
pharmacology and toxicity profiles assisting in better adherence
and far reduced failure rates. Patient management strategies and
monitoring technologies were refined, and education of clinicians
and patients on optimal aspects of care routinely was implemented.
All these have led to a new world of HIV clinical care and require a
rethinking of how best to use our knowledge of resistance and when,
how and in whom to test for it. What lays ahead for HIV drug
resistance in the near and distant future, and is it time to teach old
dogs new tricks?
Mark Wainberg; Kaitlin Anstett; Thibault Mesplede; Peter Quashie;
Yingshan Han and Maureen Oliveira
McGill University AIDS Centre, Jewish General Hospital, Montreal,
Canada.
Introduction: Drug resistance against dolutegravir (DTG) or the
nucleosides with which it has been co-administered has never been
observed in patients receiving this drug in first-line therapy. In
contrast, a R263K mutation that confers low-level resistance (34
fold) to DTG has been selected by DTG in culture. Our group has
ascribed the absence of resistance to DTG to the high fitness cost
exacted by the R263K mutation and an inability of HIV to generate
compensatory mutations.
Material and Methods: We generated recombinant integrase
enzymes and viruses containing various combinations of mutations
and studied these enzymatically and in culture. We also selected for
resistance against raltegravir (RAL) using viruses containing the
R263K mutation.
Results: The R263K mutation alone conferred an approximate 3-fold
level of resistance to DTG and a 40% loss in viral replicative capacity
and recombinant integrase activity. Secondary mutations selected at
positions H51Y or E138K did not individually affect either enzyme
activity or DTG resistance, but the combination of R263K together
with H51Y or E138K increased DTG resistance to about 7-fold accompanied by a :75% loss in each of viral replication capacity, and both
in vitro and in vivo integrase activity. Conversely, combinations of
R263K together with multiple resistance mutations for RAL and/
or EVG at positions 92,143, 148 and 155 resulted in even further
diminished enzymatic activity that may be incompatible with viral
survival. Modelling of the 3-dimensional structure of integrase suggests that R263K is located in a region that may not permit further
mutagenesis if secondary mutations at H51Y or E138K are also present.
Moreover, integrase that contains R263K together with substitutions
at positions 92, 143, 148 and 155 may be enzymatically inactive. The
use of the R263K-containing virus to select for resistance to RAL led
to the appearance of RAL-containing mutations but the loss of
R263K.
Conclusions: Secondary mutations to R263K following selection with
DTG have all led to diminished viral and enzymatic fitness, helping
to explain why resistance to DTG in previously drug-naı̈ve subjects
has never been observed. The use of DTG in first-line therapy may
prevent the facile development of drug resistance and help to
forestall ongoing HIV transmission.
O333
O332
First prospective comparison of genotypic vs phenotypic
tropism assays in predicting virologic responses to
Maraviroc (MVC) in a phase 3 study: MODERN
The R263K mutation in HIV integrase that is selected by
dolutegravir may actually prevent clinically relevant
resistance to this compound
Jayvant Heera1; Srinivas Valluri2; Charles Craig3; Annie Fang4;
Neal Thomas5; Ralph Dan Meyer5 and James Demarest6
21
Oral Abstracts
Abstract O333Table 1. MVC week 48 response (HIV-1 RNA B50c/mL), n/N (%)
MVC week 48 response (HIV-1 RNAB50c/mL), n/N (%)
Genotype R5
Trofile R5
Trofile non-R5
Trofile non-reportable
Total
226/285 (79.3)
11/14 (78.6)
14/19 (73.7)
251/318 (78.9)
Genotype non-R5
21/26 (80.8)
0
0
21/26 (80.8)
Genotype non-reportable
34/52 (65.4)
0
0
34/52 (65.4)
281/363 (77.4)
11/14 (78.6)
14/19 (73.7)
306/396 (77.3)
Total
1
Clinical Development, Pfizer Inc, Groton, USA. 2Statistics, Pfizer Inc,
New York, USA. 3Virology, Pfizer Inc, Sandwich, UK. 4Clinical
Development, Pfizer Inc, New York, USA. 5Statistics, Groton, Pfizer
Inc, USA. 6Virology, ViiV Healthcare, Research Triangle Park, USA.
Introduction: MODERN (A4001095) was the first prospective phase
3 study comparing genotype vs phenotype (TrofileTM) tropism
assessments.
Materials and Methods: Treatment-naı̈ve adults with HIV-1 RNA
1000 copies/mL were randomized 1:1 at screening to either genotype or Trofile for tropism assessment. Genotype was determined
using the geno2pheno algorithm to assess triplicate HIV-1 gp120 V3
loop sequences (plasma); false-positive rate 10%. R5-virus-infected
subjects were then randomized 1:1 to receive Maraviroc (MVC) 150
mg QD or Truvada 200/300 mg QD each with DRV/r 800/100 mg QD.
Tropism of screening samples from enrolled subjects was also retrospectively determined using the alternate testing method. Positive
predictive values (PPV) were estimated by%R5 subjects with Week
48 HIV-1 RNA B 50 c/mL. PPV for each assay was estimated using the
response rate among those randomized to that assay and using
model-based response estimates in those with R5 by that assay (at
screening or retest).
Results: The observed response rate was 146/181 (80.7%) for
genotype vs 160/215 (74.4%) for Trofile (stratification adjusted
difference6.9%, 95% CI 1.3% to 15%). The model-based estimates
of PPV (9SE) were 79.1% (92.42) and 76.3% (92.38), respectively
(difference 2.8%, 95% CI 2.1% to 7.2%). There was no difference
in response rate between assays in the Truvada arm (observed difference 0.1%, 95% CI 6.8% to 6.6%). Most enrolled subjects
had R5 results at screening using both assays (285/396 (72%)), and of
these subjects, 79.3% (226/285) had HIV-1 RNA B50 c/mL at week
48 (Table 1). The few subjects classified as non-R5 by the alternate
assay had similar virologic responses to the concordant R5 group.
Conclusion: There was a higher MVC response rate and model-based
positive predictive value with genotype compared to Trofile, but
this difference did not reach statistical significance. The majority of
subjects had concordant R5 tropism results. Either phenotype or
genotype can effectively predict MVC response.
O334
Genotypic tropism testing in proviral DNA to guide
maraviroc initiation in aviremic subjects: 48-week analysis
of the PROTEST study
Federico Garcia1; Eva Poveda2; Maria Jesús Pérez-Elı́as3;
José Hernández Quero1; Maria Àngels Ribas4; Onofre J. Martı́nezMadrid5; Juan Flores6; Manel Crespo7; Félix Gutiérrez8;
Miguel Garcı́a-Deltoro9; Arkaitz Imaz10; Antonio Ocampo11;
Arturo Artero12; Francisco Blanco13; Enrique Bernal14;
Juan Pasquau15; Carlos Mı́nguez-Gallego16; Núria Pérez17;
Aintzane Aiestarán17 and Roger Paredes18
1
Hospital Universitario San Cecilio, Granada, Spain. 2INIBIC-Complexo
Hospitalario Universitario de A Coruña, A Coruña, Spain. 3Hospital
Ramón y Cajal, Madrid, Spain. 4Hospital Son Espases, Palma de
Mallorca, Spain. 5Hospital General Universitario Santa Lucı́a,
Cartagena, Spain. 6Hospital Arnau de Vilanova, Valencia, Spain.
7
Hospital Universitari Vall d’Hebron, Barcelona, Spain. 8Hospital
Universitario de Elche, Elche, Spain. 9Hospital General Universitario
de Valencia, Valencia, Spain. 10Hospital de Bellvitge, Barcelona, Spain.
11
Hospital Xeral de Vigo, Vigo, Spain. 12Hospital Universitario Dr.
Peset, Valencia, Spain. 13Hospital Carlos III, Madrid, Spain. 14Hospital
Reina Sofı́a, Murcia, Spain. 15Hospital Virgen de la Nieves, Granada,
Spain. 16Hospital General de Castelló, Castelló, Spain. 17Hospital
Universitari Germans Trias i Pujol, Badalona, Spain. 18irsiCaixa AIDS
Research Institute, Badalona, Spain.
Introduction: In a previous interim 24-week virological safety analysis of the PROTEST study [1], initiation of Maraviroc (MVC) plus 2
nucleoside reverse-transcriptase inhibitors (NRTIs) in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA was
associated with low rates of virological failure. Here we present the
final 48-week analysis of the study.
Methods: PROTEST was a phase 4, prospective, single-arm
clinical trial (ID: NCT01378910) carried on in 24 HIV care centres in
Spain. Maraviroc-naı̈ve HIV-1-positive adults with HIV-1 RNA (VL) B50
c/mL on stable ART during the previous 6 months, requiring an ART
change due to toxicity, with no antiretroviral resistance to the ART
started, and R5 HIV by proviral DNA genotypic tropism testing (defined
as a G2P FPR 10% in a singleton), initiated MVC with 2 NRTIs and
were followed for 48 weeks. Virological failure was defined as two
consecutive VL 50 c/mL. Recent adherence was calculated as:
(# pills taken/# pills prescribed during the previous week)*100.
Results: Tropism results were available from 141/175 (80.6%) subjects screened: 87/141 (60%) were R5 and 74/87 (85%) were finally
included in the study. Their median age was 48 years, 16% were
women, 31% were MSM, 36% had CDC category C at study entry,
62% were HCV and 10% were HBV. Median CD4 counts were
616 cells/mm3 at screening, and median nadir CD4 counts were
143 cells/mm3. Previous ART included PIs in 46 (62%) subjects, NNRTIs
in 27 (36%) and integrase inhibitors (INIs) in 1 (2%). The main reasons
for treatment change were dyslipidemia (42%), gastrointestinal
symptoms (22%), and liver toxicity (15%). MVC was given alongside
TDF/FTC in 40 (54%) subjects, ABC/3TC in 30 (40%), AZT/3TC in 2
(3%) and ABC/TDF in 2 (3%). Sixty-two (84%) subjects maintained
VL B 50 c/mL through week 48, whereas 12 (16%) discontinued
treatment: two (3%) withdrew informed consent, one (1%) had a
R5 0X4 shift in HIV tropism between the screening and baseline
visits, one (1%) was lost to follow-up, one (1%) developed an ARTrelated adverse event (rash), two (3%) died due to non-study-related
causes (1 myocardial infarction at week 0 and 1 lung cancer at week
36), and five (7%) developed protocol-defined virological failure,
although two of them regained VL B 50 c/mL with the same MVC
regimen (Table 1).
Conclusions: Initiation of MVC plus 2 NRTIs in aviremic
subjects based on genotypic tropism testing of proviral HIV-1
DNA is associated with low rates of virological failure up to one
year.
22
Oral Abstracts
Subject
ART
Week
of VF
HIV-1 VL
Plasma
Recent
Resistance
at VF
(c/mL)
tropism at VF
(FPR,%)
adherence at
VF (%)
mutations at VF
(IAS-USA 2013)
ART after VF
Regained VL
B50 c/mL
1
MVC TDF/FTC
4
300
X4 (0.1)
100
NA
DRV/r ETV
Yes
2
MVC TDF/FTC
12
14,102
X4 (1.3)
100
RT: 41L, 67N, 184V,
TDF/FTC ETV
Yes
3
MVC ABC/3TC
12
67
R5 (86.8)
100
RT: 90I, 184I PR: 64V
TDF DRV/r EFV
Yes
4
MVC TDF/FTC
12
59
NA
100
NA
Continued with
MVC TDF/FTC
Yes
5
MVC TDF/FTC
36
90
R5 (79.7)
100
NA
Continued with
Yes
215Y PR: 36I, 63P
MVC TDF/FTC
Reference
1. Federico Garcı̀a, Eva Poveda, Maria Ångels Ribas, Marı́a Jesús PérezElı́as, Onofre J. Martı́nez-Madrid, Jordi Navarro, et al. Genotypic
tropism testing of proviral DNA to guide maraviroc initiation in
aviremic subjects. 21st Conference on Retroviruses and Opportunistic Infections 2014, 2014 Feb 36; Boston, US (Abstract#: 607).
O41 ARV-BASED PREVENTION
O411
Treatment as Prevention: unanswered questions and
progress to date
Stefano Vella
Department of Therapeutic Research and Medicines E, Istituto
Superiore di Sanita’, Rome, Italy.
Prevention of HIV infection has recently acquired new effective
tools, based on the provision of antiretrovirals, to both decrease the
‘‘source’’ of HIV infection and/or to decrease host susceptibility
to HIV infection. The milestone concept of using antiretrovirals for
prevention has been tested already in the 1990s, to interrupt
maternalchild. The suggestion of using antiretrovirals to decrease
inter-human HIV transmission was born already in 2006, and definitely proven by a randomized controlled study on HIV-discordant
couples demonstrating an astonishing 96% efficacy, and with numerous studies proving the efficacy of pre-exposure prophylaxis. It now
appears clear that antiretroviral therapy not only provides clinical
benefit to the individual (although the exact starting time remains
controversial, in terms of risk-benefit ratio and public health policy)
but has the potential of decreasing the incidence of new infections
at a population level. The concept of Treatment as Prevention is
now gaining momentum, as a way to progressively end the AIDS
epidemic by expanding the access to antiretrovirals, with ‘‘test and
treat’’ being the ultimate possibility, although not already tested in
the field and with huge implementation barriers. The presentation
will deal with successes, failures, and foreseen barriers of using
antiretrovirals for prevention, at the individual and population level,
also including the social issues, the need to target key-affected
populations, and, finally, the perspectives of new technologies under
development.
O412
A community perspective on pre-exposure prophylaxis
Simon Collins
HIV i-Base, London, UK.
The history of pre-exposure prophylaxis (PrEP) is notable for being a
community rather than industry-driven development. This talk will
review this history, covering factors that include community demand,
study results, regulatory challenges, commercial interests and
practical issues of public health. It will also look at some of the
controversies that appear to limit broader access, and important
changes since US approval for PrEP in 2012. If PrEP had been
discovered in the 1980s, the demand for access is likely to have been
very different and it would now be universally available. Yet in many
health settings, the willingness to include the option of PrEP appears
to be inversely correlated with the increasingly impressive data
showing its effectiveness. The limitations of condoms are shown in
continued rates of new HIV infections in high-risk populations. These
rates have remained persistently high for the last decade, even with
the dramatic impact of treatment as prevention (TasP) on reducing
further transmission. Within the last year, the polarized debate about
PrEP appears to be shifting to a middle ground focused on individual
choice. Together with TasP, this has started a new dialogue on the
potential benefits on quality of life. This has brought a new focus on
the cumulative and largely unmeasured impact for HIV negative gay
men who live for decades focused on a fear of HIV. Looking forwards,
the rate-limiting steps of cost and adherence have the potential to be
overcome with lower priced generic tenofovir in 2017 and the
development of long-acting formulations.
O42 ART STRATEGIES
O421
Efavirenz 400 mg daily remains non-inferior to 600 mg:
96 week data from the double-blind, placebo-controlled
ENCORE1 study
Dianne Carey
The Kirby Institute, University of New South Wales, Sydney, Australia.
Introduction: ENCORE1 compared the efficacy and safety of reduced
versus standard dose efavirenz (EFV) with tenofovir/emtricitabine
23
(TDF/FTC) as first-line HIV therapy. The primary analysis at 48 weeks
showed 400 mg EFV was safe and virologically non-inferior to 600 mg.
This analysis explores over 96 weeks the durability of efficacy and
safety.
Materials and Methods: A multinational, double-blind, placebocontrolled, non-inferiority trial in treatment-naı̈ve HIV-positive adults
randomized to TDF/FTC plus reduced (400 mg, EFV400) or standard
dose (600 mg, EFV600) EFV. The difference between proportions of
participants with plasma HIV RNA (VL) B200 log10copies/mL by
intention-to-treat (ITT missing failure) was compared using a noninferiority margin of 10%. Non-inferiority was also examined in
per protocol (PP) and non-completer failure (NC F) populations.
Adverse events (AEs) and serious adverse events (SAEs) were
summarized by treatment arm.
Results: The ITT population comprised 630 patients (EFV400 321;
EFV600 309); 32% were female; 37%, 33% and 30% were African,
Asian and Caucasian, respectively. A total of 585 (EFV400 299;
EFV600 286) completed 96 weeks on randomized therapy. At 96
weeks, proportions with VL B200 copies/mL were EFV400 (90.0%)
and EFV600 (90.6%) (difference 0.6; 95% CI 5.2 to 4.0; p 0.72)
demonstrating continued non-inferiority. Non-inferior efficacy was
also observed for VL thresholds of B50 and B400 copies/mL
irrespective of baseline VL ( B100,000 versus ]100,000 copies/mL).
There was no between-arm difference in time to loss of virological
response ( 200 copies/mL) (p 0.47) or mean change from baseline VL (p0.74). Mean change from baseline in CD4 T-cell counts
at week 96 remained significantly higher for EFV400 than EFV600
(difference 25 cells/mL; 95% CI 248; p 0.03). There was no
difference in the frequency or severity of AEs (EFV400 89.4%,
EFV600 89.3%; difference 0.09; 95% CI 4.73 to 4.90; p 0.97).
The proportions ever reporting an AE definitely or probably EFVrelated were EFV400 (37.7%) and EFV600 (47.9%) (difference
10.2%; 95% CI 17.9 to 2.51; p 0.01). SAEs did not differ
in frequency (EFV400 7.5%, EFV600 10.4%; difference 2.9%;
95% CI 7.3 to 1.6; p 0.20).
Conclusions: Non-inferiority of EFV 400 mg to EFV 600 mg when
combined with TDF/FTC as initial HIV therapy was confirmed at
week 96. Both doses demonstrated similar safety profiles. These
results support the use of a lower EFV dose as part of routine HIV
management.
O422
Effectiveness of a reduced dose of efavirenz plus 2 NRTIs as
maintenance antiretroviral therapy with the guidance of
therapeutic drug monitoring
Shang-Ping Yang1; Wen-Chun Liu2; Kuan-Yeh Lee3; Bing-Ru Wu2;
Yi-Ching Su2; Pei-Ying Wu1; Jun-Yu Zhang1; Yu-Zhen Luo1;
Hsin-Yun Sun2; Sui-Yuan Chang4; Shu-Wen Lin5 and
Chien-Ching Hung2
1
Center for Infection Control, National Taiwan University Hospital,
Taipei City, Taiwan. 2Internal Medicine, National Taiwan University
Hospital, Taipei City, Taiwan. 3Internal Medicine, National Taiwan
University Hospital Hsinchu Branch, Hsin-Chu city, Taiwan. 4Clinical
Laboratory Sciences and Medical Biotechno, National Taiwan
University College of Medicine, Taipei City, Taiwan. 5Graduate
Institute of Clinical Pharmacy, College of Medicine, National Taiwan
University, Taipei City, Taiwan.
Introduction: Wide inter-patient variation of plasma efavirenz (EFV)
concentrations has been observed, and a substantial proportion of
HIV-positive patients may have unnecessarily higher plasma EFV
concentrations than recommended while receiving EFV-containing
combination antiretroviral therapy (cART) at the currently recommended daily dose of 600 mg. A lower daily dose (400 mg) of EFV has
Oral Abstracts
recently been demonstrated to be as efficacious as the recommended
600 mg when combined with tenofovir/mtricitabine in a multinational clinical trial, with a lower incidence of adverse effects. We
aimed to use a therapeutic drug monitoring (TDM)-guided strategy to
optimize the EFV dose in HIV-positive Taiwanese patients.
Materials and Methods: The plasma EFV concentrations at 12 hours
(C12) after taking the previous dose were determined among HIVpositive adults who had received EFV-containing cART with viral
suppression (plasma HIV RNA load (PVL) B200 copies/mL). For
those with EFV C12 2.0 mg/L, EFV (Stocrit, MSD) was reduced to
half a tablet daily. Determinations of EFV C12 were repeated 412
weeks after switch using high-performance liquid chromatography.
CYP2B6 G516T polymorphisms were determined using polymerasechain-reaction restriction fragment-length polymorphism.
Results: Between April 2013 and June 2014, 111 patients (95.5% male;
mean age, 39 years; 96.4% with PVL B40 copies/ml; 26.4% HBsAgpositive and 7.5% anti-HCV-positive) with plasma C12 efavirenz 2.0
mg/L were switched to a reduced dose (1/2# hs) of EFV; 45.5% of
them had CYP2B6 G516T or TT genotypes; and 32.4% weighed 60 kg
or less. The mean baseline EFV C12 before switch was 3.65 mg/L
(interquartile range (IQR), 2.624.17) for 111 patients, which
decreased to 1.96 mg/L (IQR, 1.532.33) for 64 patients who had
completed follow-up of C12 EFV 4 weeks after switch, with a reduction
of 49.4% (IQR, 38.957.0%). As of 10 July, 2014, all of the 38 patients
(100%) who had completed at least one follow-up of PVL achieved
undetectable PVL (B40 copies/ml) following switch to a reduced dose
of EFV after a mean observation of 13 weeks (IQR, 715 weeks).
Conclusions: Switch to cART containing a half tablet of EFV (1/2#) in
HIV-positive Taiwanese patients with higher plasma EFV concentrations who had achieved viral suppression could maintain successful
viral suppression with the guidance of TDM.
O423A
The PROTEA trial: darunavir/ritonavir with or without
nucleoside analogues, for patients with HIV-1 RNA below
50 copies/mL
Andrea Antinori1; Jose Arribas2; Jan Fehr3; Pierre-Marie Girard4;
Andrzej Horban5; Andrew Hill6; Yvon van Delft7;
Christiane Moecklinghoff8 and Andrew Hill9
1
Infectious Diseases, National Institute of Infectious Diseases, Rome,
Italy. 2IdiPAZ, Hospital la Paz, Madrid, Spain. 3Infectious Diseases,
University Hospital Zurich, Zurich, Switzerland. 4Maladies
Infectiueses et Tropicales, Hôpital Saint-Antoine, Paris, France.
5
Infectious Diseases, Warsaw Medical University, Warsaw, Poland.
6
Janssen, R&D, High Wycombe, UK. 7Janssen, EMEA, Tilburg,
Netherlands. 8Janssen, EMEA, Neuss, Germany. 9Pharmacology and
Therapeutics, University of Liverpool, Liverpool, UK.
Introduction: In previous studies, protease inhibitor (PI) monotherapy
has shown trends for higher low-level elevations in HIV-1 RNA compared
to triple therapy, but no increase in the risk of drug resistance.
Methods:I A total of 273 patients with HIV-1 RNA B50 copies/mL
for over 24 weeks on current antiretrovirals switched to DRV/r (darunavir/
ritonavir) 800/100 mg once-daily, either as monotherapy (n137) or
with 2NRTIs (nucleoside reverse-transcriptase inhibitors) (n136),
after a 4 week run-in phase with DRV/r 2NRTI. Treatment failure was
defined as HIV-1 RNA levels above 50 copies/mL (FDA Snapshot method)
by Week 48, or switches off study treatment. Patients with elevations
in HIV-1 RNA on DRV/r monotherapy could be re-intensified with NRTIs.
The trial had 80% power to show non-inferiority for the monotherapy
arm (delta 12%).
Results: Patients were 83% male and 87% Caucasian, with mean
age 42 years; 10% were HCV antibody positive. In the DRV/r
24
Oral Abstracts
monotherapy arm, there were more patients with nadir CD4 count
below 200 cells/mL (30% versus 22%). In the primary efficacy
analysis, HIV-1 RNA B50 copies/mL by Week 48 (intent-to-treat
(ITT)) was 118/137 (86.1%) in the DRV/r monotherapy arm versus
129/136 (94.9%) in the triple therapy arm; DRV/r monotherapy did
not show non-inferiority versus triple therapy in the primary analysis
(difference 8.7%, 95% CI 15.5 to 1.8%). In the multivariate
analysis, the main predictor of treatment failure was nadir CD4
count. For patients with nadir CD4 counts B200 cells/mL, HIV-1 RNA
suppression rates at Week 48 were 27/41 (66%) in the DRV/r
monotherapy arm and 29/30 (97%) in the triple therapy arm; for
patients with CD4 nadir at least 200 cells/mL, HIV-1 RNA suppression
rates were 91/96 (95%) in the DRV/r monotherapy arm and 100/106
(94%) in the triple therapy arm. In the overall population, by a switch
included analysis, efficacy was 92.0% versus 96.3%, showing noninferiority (difference 4.3%, 95% CI 9.7 to 1.2%). No
treatment-emergent primary PI mutations were detected in three
patients with sustained elevations in HIV-1 RNA at least 400 copies/
mL (two on PI monotherapy, one on triple therapy). CD4 counts
remained stable during the trial in both arms.
Conclusions: In this study for patients with HIV-1 RNA B 50 copies/
mL at baseline, switching to DRV/r monotherapy showed lower
efficacy versus triple antiretroviral therapy at Week 48 in the primary
switch equals failure analysis (86% versus 95%). However, this lower
efficacy was seen mainly in patients with CD4 nadir levels below 200
cells/mL. There was no development of PI resistance.
O423B
Analysis of neurocognitive function and CNS endpoints in
the PROTEA trial: darunavir/ritonavir with or without
nucleoside analogues
Amanda Clarke1; Veronika Johanssen2; Jan Gerstoft3;
Bonaventura Clotet4; Diego Ripamonti5; Andrew Murungi6;
Ceyhun Bicer7; Maria Blanca Hadacek8 and Christiane Moecklinghoff9
1
HIV and Sexual Health, Brighton and Sussex Medical School,
Brighton, UK. 2Infectious Diseases, Karolinkska University, Sjukhuset,
Sweden. 3Infectious Diseases, Copenhagen University Hospital,
Copenhagen, Denmark. 4irsiCaixa, University Hospital Germans Trias i
Pujol, Badalona, Spain. 5Infectious Diseases, University Hospital,
Bergamo, Italy. 6Janssen, HIV, High Wycombe, UK. 7Janssen, R&D,
Beerse, Belgium. 8Janssen, EMEA, Issy-les-Moulineux, France.
9
Janssen, EMEA, Neuss, Germany.
Introduction: During treatment with protease inhibitor monotherapy, the number of antiretrovirals with therapeutic concentrations in
the cerebrospinal fluid (CSF) is lower, compared to standard triple
therapy. However, the clinical consequences are unclear.
Methods: A total of 273 patients with HIV RNA B50 copies/mL for
over 24 weeks on current antiretrovirals randomized to darunavir/
ritonavir (DRV/r) 800/100 mg once-daily, either as monotherapy
(n 137) or with 2NRTIs (n 136). Neurocognitive function was
evaluated in all patients by the Hopkins Verbal Learning Tests, the
Colour Trail Tests and the Grooved Pegboard Test at screening,
baseline and at Week 48. A global neurocognitive score (NPZ-5) was
derived by averaging the standardized results of the five domains.
In a central nervous system (CNS) sub-study (n 70), HIV RNA levels
in the CNS were evaluated at baseline and Week 48. Clinical adverse
events related to the CNS were collected at each visit.
Results: Patients were 83% male and 88% White, with median age 43
years. There were more patients with nadir CD4 count below 200
cells/mL in the DRV/r monotherapy arm (41/137, 30%) than the triple
therapy arm (30/136, 22%). At Week 48, there was no difference
between the treatment arms for the five combined domains of the
neurocognitive score. At Week 48, the percentage of patients with an
abnormal neurocognitive score among the five domains was 12.2%
for DRV/r monotherapy and 14.9% for triple therapy. However, one
patient on DRV/r monotherapy with a CD4 nadir of 17 cells/mL was
hospitalized with HIV encephalomyelitis at Week 24, with HIV RNA
2500 copies/mL in the CSF and 125 copies/mL in the plasma.
Symptoms resolved after intensification with high dose zidovudine.
A second patient on DRV/r monotherapy with CD4 nadir of 166 cells/
mL had a rise in HIV RNA in CSF from B40 copies/mL at baseline to
654 copies/mL at Week 48, with concurrent plasma HIV RNA of 77
copies/mL.
Conclusions: In this study for patients with HIV RNA B50 copies/mL
at baseline, there was no difference in neurocognitive function
between the treatment arms. However two patients on PI monotherapy with CD4 nadir B200 cells/mL developed viraemia in both
CSF and plasma, with one symptomatic case. DRV/r monotherapy
should be used with caution in patients with nadir CD4 counts below
200 cells/mL.
O424
Rate of viral load failure over time in people on ART in the
UK Collaborative HIV Cohort (CHIC) study
Jemma O’Connor1; Colette Smith1; Fiona Lampe1;
Margaret Johnson2; Caroline Sabin1 and Andrew Phillips1
1
Department of Infection and Population Health, UCL, London, UK.
2
Ian Charleson Day Centre, Royal Free Hampstead NHS Trust,
London, UK.
Abstract O424Table 1. Rate per 100 person-years of viral load failure over time since start of ART
Single VL 200 copies/mL (two
consecutive VL 1000 copies/mL)
Follow-up on ART,
years (x)
Number in risk set at
start of period
Number of VL failures
during period
Rate of VL failure per 95% confidence interval for rate
100 person-years
of VL failure
0x 5 2
13,556 (12,811)
4,075 (3,376)
30.1 (26.4)
29.230.8 (25.627.1)
2x 5 4
7,310 (7,710)
801 (577)
11.0 (7.5)
10.311.7 (6.98.1)
4x 5 6
3,992 (4,434)
305 (204)
7.6 (4.6)
7.28.8 (4.05.2)
6x 5 8
2,085 (2,426)
128 (89)
6.1 (3.7)
5.07.0 (2.94.4)
8x 5 10
805 (980)
38 (26)
4.7 (2.7)
3.56.5 (1.63.7)
10x 5 11.5
179 (220)
4 (2)
2.2 (0.9)
0.43.8 (0.12.4)
25
Introduction: Most people achieve and maintain viral load (VL) suppression on first-line antiretroviral therapy (ART) but for a minority
this does not happen. It is unclear whether those who have maintained VL suppression for several years will be able to continue to do
so, or if rates of VL failure due to poor adherence, ART interruption
and/or resistance remain at appreciable levels.
Methods: Eligible participants were ART-naı̈ve and started treatment after 1st January 2000, with ]3 antiretrovirals and ]9
months follow-up. VL failure was defined as failure to achieve VL
suppression ( 550 copies/mL) by 9 months on ART or a single VL
200 copies/mL after 9 months after start of ART. KaplanMeier estimates were used to examine the cumulative probability of experiencing a VL 200 copies/mL over time, irrespective of
treatment interruption (Figure 1). Follow-up was censored at last
VL assessment but not at treatment interruption. In a sensitivity
analysis, VL failure was instead defined as two consecutive VL
1000 copies/mL.
Results: A total of 13,556 participants were included. Median (IQR)
age at start of ART was 37 (3243), median follow-up 4.1 (2.36.7)
years, pre-ART VL 71,400 (17,400221,900) copies/mL and pre-ART
CD4 count 204 (110290) cells/mm3. Fifty-one percent were white,
71% male and 50% MSM. Of which, 5,351 (39%) participants
experienced a VL 200 copies/mL. In sub-groups of participants
the proportion experiencing a VL 200 copies/mL by one year after
start of ART were: B50 years 22%, ]50 years 17%, men 20%,
women 26%, MSM 19%, black heterosexuals 23%, white heterosexuals 26% and other 23%. The median time to VL 200 copies/ml
was 8 years. In sensitivity analyses based on 12,811 participants,
4274 (33%) experienced two consecutive VL 1000 copies/mL.
Table 1 presents the rate of experiencing a VL 200 copies/mL (two
consecutive VL 1000 copies/mL) by time since start of ART. The
rate of VL 200 copies/mL declines over time, from 30 per 100
person-years after up to two years after ART, to two per 100 personyears after up to 11.5 years after ART. A sum of 2,047 (15%)
participants stopped ART at some point (10, 14 and 17% had stopped
ART by 1, 3, and 5 years, respectively).
Conclusions: Although resistance will often not be present and, even
if present, several drug options will likely remain, first occurrence of
VL 200 copies/mL after having attained viral suppression continues to occur after 10 years on ART.
Oral Abstracts
O43 NEW HIV DRUGS
O431
HIV treatment 2020: what will it look like?
Roy Gulick
Department of Medicine, Weill Medical College of Cornell University,
New York, USA.
Currently there are 28 approved antiretroviral drugs in six mechanistic
classes, and recommended first-line regimens are highly potent, well
tolerated, and as convenient as one pill, once-a-day. How will HIV
treatment change by 2020? Over the next few years, we are likely to
see potent 2-drug regimens tested head-to-head with standard threedrug regimens, and some of these will likely become standard-of-care.
Newer agents with novel drug resistance profiles (e.g. doravirine,
an NNRTI) or new mechanisms of action (e.g. BMS 663068, a CD4
attachment inhibitor) will provide virologic activity in patients with
drug-resistant viral strains. Comparative studies of current and newer
agents such as the investigational prodrug of tenofovir (TAF) will help
define less toxic regimens. We will see additional convenient coformulations developed; with them, we are likely to have second- and
even third-line regimens administered one pill, once-daily. Longacting injectable investigational formulations currently in clinical
trials such as rilpivirine LA (administered monthly) and cabotegravir
(administered quarterly), and others (including combinations of these
agents) could provide additional convenient treatment options. Other
novel formulations (e.g. patches, implants, rings) and combinations of
antiretrovirals with other kinds of medications (e.g. contraceptives)
may be developed and tested. In the developing world, we will
see increasing numbers of patients taking potent, well-tolerated
convenient first-line and subsequent regimens with the goal of ‘‘20 by
20’’ 20 million treated people by 2020. Generic formulations of
antiretroviral drugs, including combinations, will be increasingly
available and used worldwide. With the current appreciation that
inflammation and immune activation play an important role in the
natural history of treated HIV infection, anti-inflammatory agents will
be tested and may supplement (or even be co-formulated with)
standard antiretroviral regimens. Recognizing our progress to date,
these and other innovations will further improve HIV therapy by 2020.
O432A
HIV-1 attachment inhibitor prodrug BMS-663068 in
antiretroviral-experienced subjects: week 24 sub-group
analysis
Cynthia Brinson1; Jacob Lalezari2; Latiff H Gulam3;
Melanie Thompson4; Juan Echevarria5; Sandra Treviño-Pérez6;
David Stock7; Joshi R Samit7; Hanna J George8 and Max Lataillade7
1
Family Medicine, Austin Branch and Central Texas Clinical Research,
Southwestern Medical School, Austin, TX, USA. 2Quest Clinical
Research, N/A, San Francisco, CA, USA. 3Maxwell Clinic, N/A, Durban,
South Africa. 4AIDS Research Consortium of Atlanta, N/A,
Atlanta, GA, USA. 5Infectious and Tropical Medicine, Hospital
Nacional Cayetano Heredia, Lima, Peru. 6HIV Research Department,
Mexico Centre for Clinical Research, Mexico City, Mexico. 7Research
and Development, Bristol-Myers Squibb, Wallingford, CT, USA.
8
Research and Development, Bristol-Myers Squibb, Princeton,
NJ, USA.
Abstract O424Figure 1. Kaplan-Meier plot of time to viral load
failure (single VL 200 copies/mL) since initiation of ART.
Introduction: BMS-663068 is a prodrug of BMS-626529, an attachment inhibitor that binds directly to HIV-1 gp120, preventing initial
viral attachment and entry into the host CD4 T-cell. AI438011 is
26
a Phase IIb, randomized, active-controlled trial investigating the
safety, efficacy and doseresponse of BMS-663068 versus atazanavir/ritonavir (ATV/r) in treatment-experienced (TE), HIV-1-positive
subjects.
Materials and Methods: Antiretroviral TE subjects (exposure to ]1
antiretroviral for ]1 week) with susceptibility to all study drugs
(BMS-626529 IC50 100 nM), were randomized equally to four BMS663068 arms (400 or 800 mg, BID; 600 or 1200 mg, QD) and a control
group (ATV/r 300/100 mg QD) with tenofovir disoproxil fumarate
(TDF) raltegravir (RAL). A sub-group analysis of viral efficacy and
immunologic reconstitution is presented.
Results: A total of 251 subjects were treated. Median age was 39
years, 60% were male and 38% were white. Median baseline (BL)
viral load (VL) was 4.85 log10 c/mL (43%; 100,000 c/mL) and median
CD4 T-cell count was 230 cells/mm3 (38%; 200 CD4 cells/mm3).
Through Week 24, response rates (HIV-1 RNA 50 c/mL) were comparable across all BMS-663068 arms and the ATV/r arm regardless of
gender, age and race. Response rates for subjects with BL VL 100,000
c/mL (BMS-663068, 82-96%; ATV/r, 93%) were higher than those for
subjects with BL VL ]100,000 c/mL (BMS-663068, 70-87%; ATV/r,
73%); however, there were no substantial differences in response
across the BMS-663068 and ATV/r arms in either sub-group. Response rates for subjects with BL CD4 cell counts ]200 cells/mm3
(87-96%) were higher than those for subjects with BL CD4 cell
counts 200 cells/mm3 (6282%); however, no substantial differences
in response were seen across the BMS-663068 and ATV/r arms in
either sub-group. Mean changes in CD4 T-cell counts from BL were
similar across all arms regardless of gender, age and BL CD4 T-cell
count.
Conclusion: Virologic response rates were similar across the BMS663068 and ATV/r arms in TE subjects, regardless of BL demographic
characteristics (gender, race, age), BL HIV-1 RNA, or BL CD4 T-cell
count. Mean increases in CD4 T-cell counts across the BMS-663068
arms were consistent with ATV/r, regardless of gender, age and BL
CD4 T-cell count. These results support continued development of
BMS-663068.
Note:
Previously submitted at IDWeek, Philadelphia, PA, 8 October 2014.
O432B
Safety profile of HIV-1 attachment inhibitor prodrug
BMS-663068 in antiretroviral-experienced subjects:
week 24 analysis
Jacob Lalezari1; Gulam H Latiff2; Cynthia Brinson3; Juan Echevarria4;
Sandra Treviño-Pérez5; Johannes R Bogner6; David Stock7; Samit R
Joshi7; George J Hanna8 and Max Lataillade7
1
Quest Clinical Research, N/A, San Francisco, CA, USA. 2Maxwell
Clinic, N/A, Durban, South Africa. 3Family Medicine, Southwestern
Medical School, Austin Branch and Central Texas Clinical Research,
Austin, TX, USA. 4Hospital Nacional Cayetano Heredia, Lima, Peru.
5
HIV Research Department, Mexico Centre for Clinical Research,
Mexico City, Mexico. 6Section for Infectious Diseases, Med. IV,
Hospital of the University of Munich, Munich, Germany. 7Research
and Development, Bristol-Myers Squibb, Wallingford, CT, USA.
8
Research and Development, Bristol-Myers Squibb, Princeton,
NJ, USA.
Introduction: BMS-663068 is a prodrug of BMS-626529, an attachment inhibitor that binds directly to HIV-1 gp120, preventing initial
viral attachment and entry into the host CD4 T-cell. AI438011 is an
ongoing, Phase IIb, randomized, active-controlled trial investigating
the safety, efficacy and doseresponse of BMS-663068 vs. atazana-
Oral Abstracts
vir/ritonavir (ATV/r) in treatment-experienced (TE), HIV-1-positive
subjects. At Week 24, response rates across the BMS-663068 arms
were consistent with ATV/r.
Materials and Methods: Antiretroviral TE subjects (exposure to ]1
antiretroviral for ]1 week) with susceptibility to all study drugs
(including BMS-626529 IC50 100 nM) were randomized equally to
four BMS-663068 arms (400 or 800 mg, BID; 600 or 1200 mg, QD)
and a control arm (ATV/r 300/100 mg QD), with tenofovir disoproxil
fumarate (TDF) raltegravir (RAL). The complete safety profile
through Week 24 is reported.
Results: In total, 251 subjects were treated (BMS-663068, 200; ATV/r,
51). No BMS-663068-related adverse events (AEs) led to discontinuation. Grade 24 drug-related AEs occurred in 17/200 (8.5%)
subjects across the BMS-633068 arms; however, these events were
mostly single instances and no dose-relationship was seen. Similarly,
no noticeable trend for Grade 34 laboratory abnormalities was
seen and Grade 34 hematologic changes and liver chemistry elevations were uncommon (neutropenia, 2.5%; AST/ALT elevations, 1%
(n 196)). In the ATV/r arm, Grade 24 drug-related AEs occurred in
14/51 (27.5%) subjects and were mostly secondary to gastrointestinal and/or hepatobiliary disorders. Serious adverse events (SAEs)
occurred in 13/200 (6.5%) and 5/51 (9.8%) subjects receiving BMS663068 and ATV/r, respectively; most were secondary to infections
and none were related to study drugs. The most common AE
reported for BMS-663068 was headache (28/200, 14%), occurring in
5/51 (10%) subjects in the ATV/r arm; in the BMS-663068 arms, this
was not dose-related. There were no deaths.
Conclusion: BMS-663068 was generally well tolerated across all
arms, with no related SAEs or AEs leading to discontinuation and no
dose-related safety signals. There were no trends for Grade 24 AEs
or clinical laboratory abnormalities. These results support continued
development of BMS-663068.
Note:
Previously submitted at IDWeek, Philadelphia, PA, 8 October 2014.
O433
Cenicriviroc blocks HIV entry but does not lead to
redistribution of HIV into extracellular space like maraviroc
Victor Kramer1; Said Hassounah1; Susan Colby-Germinario1;
Thibault Mesplède1; Eric Lefebvre2 and Mark Wainberg1
1
McGill AIDS Centre, Lady Davis Institute, Jewish General Hospital,
Montreal, QC, Canada. 2Tobira Therapeutics, Inc., South San
Francisco, CA, USA.
Introduction: Cenicriviroc (CVC), a once-daily, dual CCR5/CCR2 coreceptor antagonist, has completed Phase 2b development. CVC
demonstrated favourable safety and similar efficacy compared with
efavirenz (EFV) in Study 202 (NCT01338883); an ex vivo sub-analysis
evaluated treatment effects on HIV entry, measured by intracellular
HIV DNA declines, in subjects with virologic success at Week 24. In
addition, in vitro assays determined and compared the extent of any
cell-free virion redistribution that CVC or maraviroc (MVC) may cause.
Methods: Ex vivo: intracellular DNA (frozen PBMCs) from 30 subjects
with virologic success at Week 24 (10, 13 and 7 subjects on CVC 100
mg, CVC 200 mg and EFV, respectively). Early (strong-stop) and late
(full-length) reverse transcript levels were measured by qPCR.
In vitro: PM-1 cells were infected with CCR5-tropic HIV-1 BaL in
the presence or absence of inhibitory concentrations of CVC (20 nM),
MVC (50 nM) or controls. P24 and viral load levels were measured by
ELISA and qRT-PCR after 4 hours.
Results: Ex vivo analysis showed full-length HIV DNA declines were
similar across all groups (CVC 100 mg, CVC 200 mg and EFV) at Week
24. Strong-stop HIV DNA declines (a marker of HIV entry) at Week 24
27
were pronounced for both CVC arms (CVC 100 mg, 51% decline; CVC
200 mg, 37% decline) compared to no decline for the EFV arm.
In vitro experiments revealed that CVC-treated cells had lower levels
of supernatant P24 at 4 hours versus baseline (0 hrs: 506 ng/mL;
4 hrs: 192 ng/mL), but P24 levels remained constant for MVC-treated
cells after 4 hours (0 hrs: 506 ng/mL; 4 hrs: 520 ng/mL). Viral load
levels for CVC-treated cells remained stable after 4 hours (0 hrs:
1.191010 copies/mL; 4 hrs: 1.261010 copies/mL). MVC-treated
cells exhibited a slight increase in viral load after 4 hours (0 hrs:
1.191010 copies/mL; 4 hrs: 1.671010 copies/mL).
Conclusions: Ex vivo analysis confirmed that CVC treatment blocks
HIV entry (strong-stop HIV DNA declines), while in vitro analysis
showed that CVC-treated cells do not repel virus back into the
extracellular space, as seen with MVC. Experiments are underway to
determine whether or not interactions between CVC and HIV at the
binding site may explain these unanticipated findings.
19531
O434
Forty-eight-week efficacy and safety and early CNS
tolerability of doravirine (MK-1439), a novel NNRTI, with
TDF/FTC in ART-naive HIV-positive patients
Josep M Gatell1; Javier O Morales-Ramirez2; Debbie P Hagins3;
Melanie Thompson4; Arasteh Keikawus5; Christian Hoffmann6;
Sorin Rugina7; Olayemi Osiyemi8; Simona Escoriu7; Robin Dretler9;
Charlotte Harvey10; Xia Xu10 and Hedy Teppler10
1
Hospital Clinic/IDIBAPS, University of Barcelona, Barcelona, Spain.
2
Clinical Research, Clinical Research Puerto Rico, San Juan, Puerto
Rico. 3Country Health Department, Chatham Country Health,
Savannah, USA. 4AIDS Research Consortium of Atlanta, Atlanta, USA.
5
EPIMED/Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany. 6ICH
Study Center, Hamburg, Germany. 7Spitalul Clinic de Boli Infectioase,
Costanta, Romania. 8Triple O Research Institute PA, West Palm Beach,
USA. 9Infectious Disease Specialists of Atlanta, Decatur, USA. 10Merck
& Co. Inc, Whitehouse Station, New Jersey, USA.
Oral Abstracts
Proportion of
patients with
virologic
response
(95% CI)
Week 48
efficacy
(Part 1)
Treatment$
(mg)
Doravirine
qd
N
25
40
50 43
100 42
200 41
All 166
Efavirenz qhs 600 42
Missing data
approach:
$
Mean CD4
change from
baseline
(95% CI)
HIV RNA
B40 c/mL
HIV RNA
B200
c/mL
cells/mL
73 (56, 85)
85 (70, 94)
190 (144, 236)
72
76
83
76
71
(56,
(61,
(68,
(69,
(55,
85)
88)
93)
82)
84)
74 (59, 87)
134 (78, 190)
86 (72, 95)
155 (117, 194)
85 (71, 94)
194 (134, 253)
83 (76, 88)
168 (143, 193)
79 (63, 90)
179 (127, 230)
Non-completer
Observed
failure
failure
In combination with TDF/FTC.
Doravirine
Efavirenz
Week 48 safety (Part 1)
(N166)
(N42)
%
%
One or more clinical AEs
88.0
83.3
Drug-related (DR) AEs
36.7
57.1
Serious AE
4.8
9.5
Serious and DR AE
0.0
0.0
Discontinued due to AE
4.2
4.8
Discontinued due to DR AE*
2.4
4.8
Discontinued due to serious AE
0.6
0.0
*All discontinuations due to DR AE occurred by week 24.
Introduction: Doravirine (DOR) is an investigational NNRTI (aka MK1439) that retains activity against common NNRTI-resistant mutants.
We have previously reported the Part 1 results from a two-part,
randomized, double-blind, Phase IIb study in ART-naı̈ve HIV-1positive patients [1]. At doses of 25, 50, 100 and 200 mg qd, DOR
plus open-label tenofovir/emtricitabine (TDF/FTC) demonstrated
potent antiretroviral activity comparable to EFV 600 mg qhs plus
TDF/FTC and was generally well tolerated at week 24. DOR 100 mg
was selected for use in patients continuing in Part 1 and those newly
enrolled in Part 2.
Methods: Patients receiving DOR 25, 50 or 200 mg in Part 1 were
switched to 100 mg after dose selection. In Part 2, 132 additional
patients were randomized 1:1 to DOR 100 mg qd or EFV 600 mg qhs
(each with TDF/FTC). We present week 48 efficacy and safety results
for all patients in Part 1, and early (week 8) CNS tolerability only for
patients randomized to DOR 100 mg or to EFV in Parts 1 and 2
combined. The primary safety endpoint is the % of patients with prespecified CNS events (all causality) by week 8 for DOR 100 mg qd vs
EFV (Parts 1 2 combined).
Results: Part 1 week 48 efficacy and safety results are shown below.
The most common DR clinical AEs in the DOR and EFV groups,
respectively, were abnormal dreams (10.2%; 9.5%), nausea (7.8%;
2.4%), fatigue (7.2%; 4.8%), diarrhoea (4.8%; 9.5%) and dizziness
(3.0%; 23.8%), and were generally mild to moderate.
Part 1 2 Week 8 CNS Event Analysis: One hundred thirty-two
patients were randomized in Part 2, 66 to DOR 100 mg and 66 to EFV.
Combining Part 1 and 2, a total of 108 patients received DOR 100 mg
and 108 received EFV. By week 8, at least one CNS AE was reported
in 22.2% of the DOR group and 43.5% of the EFV group (p B0.001).
The most common CNS AEs were dizziness (DOR 9.3%; EFV 27.8%),
insomnia (6.5%; 2.8%), abnormal dreams (5.6%; 16.7%) and nightmares (5.6%; 8.3%).
Conclusions: In ART-naı̈ve, HIV-1-positive patients also receiving TDF/
FTC, DOR 100 mg qd demonstrated potent antiretroviral activity and
immunological effect at week 48 and was generally safe and well
tolerated. Patients who received DOR 100 mg qd had significantly
fewer treatment-emergent CNS AEs by week 8 than those who
received EFV.
Reference
1. Morales-Ramirez J, Gatell J, Hagins D, Thompson M, Arastéh K,
Hoffmann C, et al. Safety & Antiviral Effect of MK-1439, a novel
NNRTI, (TDF/FTC) in ART-Naive HIV Infected Patients. Conference
on Retroviruses and Opportunistic Infections (CROI) 2014 Program
and Abstracts [Abstr 92LB], March 2014, IAS-USA, San Francisco, CA.
28
Poster Abstracts
POSTER ABSTRACTS
ADHERENCE
P001
Socio-economic factors and virological suppression among
people diagnosed with HIV in the United Kingdom: results
from the ASTRA study
Lisa Burch1; Colette Smith1; Jane Anderson2; Lorraine Sherr1;
Alison Rodger1; Rebecca O’Connell3; Richard Gilson1;
Jonathan Elford4; Andrew Phillips1; Andrew Speakman1;
Margaret Johnson5 and Fiona Lampe1
1
London, London, UK. 2Centre for the study of Sexual Health and HIV,
Homerton University Hospital, London, UK. 3Department of Sexual
Health, Newham University NHS Hospital Trust, Barts Health, London,
UK. 4School of Health Sciences, City University London, London, UK.
5
Department of HIV Medicine, Royal Free NHS London Foundation
Trust, London, UK.
Introduction: In the United Kingdom, rates of virological
suppression on antiretroviral therapy (ART) are very high, but
there remain a small but significant number of people on
ART with detectable viraemia. The impact of socio-economic
factors on virological suppression has been little studied.
Materials and Methods: We used data from ASTRA, a crosssectional, questionnaire study of 3000 individuals from 8
clinics in the United Kingdom in 20112012, linked to clinical
Abstract P001Table 1.
records to address this question. Included participants had
received ART for 6 months with a recorded current viral
load (VL) (latest at the time of questionnaire). Participants
provided data on demographic factors: gender, sexual orientation, ethnicity and age; and socio-economic factors: UK
birth/English reading ability, employment, housing, education
and financial hardship. To assess non-adherence, participants
were asked if in the past 3 months, they had missed ART for
]2 days at a time. Virological suppression was defined as
VL 550 cps/mL. For each socio-economic factor, we calculated prevalence ratios using modified Poisson regression,
first adjusting for demographic factors, then also for nonadherence.
Results: A total of 2445 people fulfilled the inclusion criteria
(80% male, 69% MSM, median age: 46 years, median CD4
count: 556 cells/mm3); 10% (234/2445) had VL 50 cps/mL.
After adjusting for demographic factors, non-fluent English,
not being employed, not home owning, education below
university level and increasing financial hardship were each
associated with higher prevalence of VL50 cps/mL. Additional adjustment for non-adherence largely attenuated each
association, but did not fully explain them (see Table 1). After
adjustment for non-adherence and demographic factors,
younger age was also associated with VL 50 cps/mL: for
each additional 10 years an individual was 0.80 (95% CI 0.70
0.92) times as likely to have VL 50 cps/mL (p 0.0019).
Association between socio-economic factors and having VL 50 copies/mL
VL 50 copies/
Adjusted for
Adjusted for demographic
mL
demographic factorsa
factors and non-adherenceb
Socio-economic
N (%)
factors
Overall
English reading
ability
Employed
Homeowner
University
a
Prevalence Ratio (95% CI)
p
Prevalence Ratio (95% CI)
p
234/2445 (10%)
Born in the
114/1337 (9%)
0.0021
1.00
0.0389
1.00
0.3058
UK
Fluent
73/841 (9%)
0.75 (0.54, 1.05)
Not fluent
Yes
34/185 (18%)
95/1316 (7%)
1.28 (0.79, 2.05)
1.00
No
139/1129 (12%)
Yes
44/861 (5%)
No
181/1537 (12%)
Yes
72/986 (7%)
No
149/1390 (11%)
Enough money for Always
basic needs?
p
66/1050 (6%)
Mostly
Sometimes
66/626 (11%)
48/423 (11%)
No
45/298 (15%)
B.0001
0.85 (0.62, 1.17)
B.0001
1.80 (1.39, 2.34)
B.0001
1.00
1.00
B.0001
1.00
1.00
0.0007
1.74 (1.23, 2.45)
0.0011
1.55 (1.18, 2.04)
B.0001
0.0057
1.44 (1.11, 1.87)
2.07 (1.48, 2.91)
0.0051
1.18 (0.73, 1.89)
1.00
1.00
0.0214
1.36 (1.04, 1.78)
0.0001
1.00
1.68 (1.20, 2.34)
1.71 (1.18, 2.50)
1.46 (1.05, 2.03)
1.29 (0.88, 1.89)
2.32 (1.60, 3.37)
1.77 (1.21, 2.59)
0.0224
b
Adjusted for age, gender, sexual orientation and ethnicity; adjusted for demographics and ART non-adherence self-reported ever missed ]2
days.
Test for trend.
29
Poster Abstracts
Adjusted prevalence ratios for VL 50cps/mL were 0.91
(0.621.34) for women and 1.25 (0.851.84) for non-MSM
men versus MSM, and 1.29 (0.921.80) for white versus nonwhite people.
Conclusions: Among people on ART in the United Kingdom,
the proportion with detectable VL is low. Poorer socioeconomic status is associated with increased probability of
virological non-suppression. It is likely that much of this
association is mediated through difficulties in taking ART.
Emphasis should be put on aiding the adherence of people in
these higher risk groups.
P002
Factors associated with the continuum of care of HIVinfected patients in Belgium
Dominique Van Beckhoven1; Patrick Lacor2; Michel Moutschen3;
Denis Piérard4; André Sasse1; Dolorès Vaira5; Sigi Van den Wijngaert6;
Risk factors
Bernard Vandercam7; Marc Van Ranst8; Eric Van Wijngaerden9;
Linos Vandekerckhove10; Chris Verhofstede11; Ruth Verbrugge1;
Rémy Demeester12; Stéphane De Wit13; Eric Florence14;
Katrien Fransen15; Marie-Luce Delforge16; Jean-Christophe Goffard17;
Patrick Goubau18 and BREACH19
1
Epidemiology of Infectious Diseases Unit, Scientific Institute of
Public Health, Brussels, Belgium. 2AIDS Reference Center, Universitair
Ziekenhuis Brussel, Brussels, Belgium. 3AIDS Reference Center, CHU
de Liège, Liege, Belgium. 4AIDS Reference Laboratory, Universitair
Ziekenhuis Brussel, Brussels, Belgium. 5AIDS Reference Laboratory,
Liège University, Liege, Belgium. 6Laboratory of Microbiology, CHU
Saint-Pierre, Brussels, Belgium. 7AIDS Reference Center, Cliniques
Universitaires Saint-Luc, Brussels, Belgium. 8AIDS Reference
Laboratory, KU Leuven, Leuven, Belgium. 9AIDS Reference Center, UZ
Leuven, Leuven, Belgium. 10UZ Gent, AIDS Reference Center, Ghent,
Belgium. 11UZ Gent, AIDS Reference Laboratory, Ghent, Belgium.
12
AIDS Reference Center, CHU de Charleroi, Charleroi, Belgium.
13
AIDS Reference Center, CHU Saint-Pierre, Brussels, Belgium. 14AIDS
Reference Center, Instituut Tropische Geneeskunde, Antwerp,
Belgium. 15AIDS Reference Laboratory, Instituut Tropische
Adjusted OR for factors associated with each step of the continuum of HIV care
Adjusted OR
Adjusted OR
Adjusted OR
Adjusted OR
Adjusted OR (95% CI)a
(95% CI)a No
(95% CI)a No
(95% CI)a
(95% CI)a Suppressed VL
Undiagnosed HIV entry in care
retention
On ART
( B500 cp/ml)
1
1.32 (0.394.44)
1
0.88 (0.581.34)
1
0.87 (0.701.07)
1
0.76 (0.551.04)b
1
1.02 (0.731.42)
Sex
Male
Female
Age at diagnosis
B40 yrs
1
1
1
1
1
]40 yrs
0.42 (0.270.64)
0.98 (0.691.39)
1.05 (0.861.28)
1.31 (1.041.65)b
1.75 (1.272.42)
Way of
transmission
Heterosexual
MSM
IDU
1
1
1
1
1
0.39 (0.160.95)
/
0.86 (0.521.44)
1.50 (0.554.11)
0.61 (0.470.78)
1.88 (1.222.88)
0.80 (0.581.09)b
2.42 (0.698.46)b
1.06 (0.721.56)
1.46 (0.524.11)
Region of origin
Belgium
Sub-Saharan
1
1
1
1
1
1.02 (0.333.14)
3.11 (1.845.26)
1.41 (1.121.78)
0.90 (0.661.23)b
0.73 (0.511.03)b
0.83 (0.411.69)
2.74 (1.594.71)
1.86 (1.382.52)
0.97 (0.671.40)b
0.97 (0.571.66)b
b
Africa
Europe
Other
2.25 (1.264.04)
3.23 (1.795.83)
1.54 (1.102.17)
0.90 (0.591.37)
0.89 (0.511.48)
/
1
1
1
/
0.98 (0.641.50)
0.95 (0.741.21)
1.76 (1.342.31)b
0.92 (0.631.35)
Prenatal
/
1.14 (0.512.52)
1.16 (0.751.78)
0.49 (0.300.81)b
0.42 (0.230.78)
Preoperative
/
3.22 (1.506.89)
1.21 (0.722.04)
1.14 (0.562.31)b
0.85 (0.352.04)
Other
CD4 at first visit
/
0.92 (0.551.54)
1.13 (0.861.49)
1.54 (1.112.14)b
1.03 (0.651.63)
Reason for
testing
Patient’s
1
request
Clinical
arguments
CD4 ]350
/
/
1
1
CD4 B350
/
/
1.16 (0.891.51)
8.02 (5.8011.11)
1
1.16 (0.781.70)
Note: Rem: pB0.05, statistically significant variables presented in italic.
a
Adjusted for sex, age at diagnosis, nationality and ay of transmission; badditionally adjusted for CD4 value at first visit.
30
Poster Abstracts
Abstract P002Figure 1. The continuum of HIV care in Belgium.
Geneeskunde, Antwerp, Belgium. 16AIDS Reference Laboratory,
University Hospital ULB Erasme, Brussels, Belgium. 17AIDS Reference
Center, University Hospital ULB Erasme, Brussels, Belgium. 18AIDS
Reference Laboratory, Université Catholique de Louvain, Brussels,
Belgium. 19Belgian Research on AIDS and HIV Consortium, Belgium.
Introduction: We studied factors associated with the continuum of HIV care in Belgium.
Methods: Data of the national registration of new HIV
diagnosis and of the national cohort of HIV-infected patients
in care were combined to obtain estimates of and factors
related with proportions of HIV-infected patients in each step
of the continuum of care from diagnosis to suppressed viral
load (VL). Factors associated with ignorance of HIV seropositivity were analyzed among patients co-infected with HIV and
STI in the Belgian STI sentinel surveillance network. Associated
factors were identified by multivariate logistic regression.
Results: Among 4038 individuals diagnosed with HIV between
2007 and 2010, 90.3% were linked to care. Of 11684 patients
in care in 2010, 90.8% were retained in care up to the following year, 88.3% of those were on ART, of whom 95.3% had
suppressed VL (B500 cp/ml) (Figure 1). In multivariate
analyses, factors associated with ignoring HIV status were
being younger (p B0.001), being heterosexual compared to
MSM, and of a region of origin other than Belgium, SubSaharan Africa and Europe. Non-Belgian regions of origin were
associated with lower entry and retention in care (p B0.001
for both). Preoperative HIV testing was associated with lower
entry in care (p 0.003). MSM had a higher retention in care
(p B0.001), whilst IDU had lower retention (p 0.004). Low
CD4 at first clinical contact and clinical reasons for HIV testing
were independently associated with being on ART (p B0.001
for both); whilst prenatal HIV diagnosis was associated with
lower proportion on ART (p 0.016) and lower proportion
with suppressed VL among those on ART (p 0.005). Older age
was associated with both being on ART and having suppressed
VL among those on ART (p 0.007 and pB0.001 respectively),
independently of time since HIV diagnosis (Table 1).
Conclusions: Regions of origin and risk groups (MSM/
heterosexual/IDU) are the main factors associated with
ignorance of HIV seropositivity, entry and retention in care,
but once the HIV patient is retained in care, no effect of
these factors on the proportions on ART and with suppressed
VL are observed. The association of prenatal HIV diagnosis
and proportions on ART and with suppressed VL could be
biased by transitory CD4 disturbances during pregnancy and
ART discontinuation after pregnancy. The higher probabilities
of older patients to be on ART and have suppressed VL once
retained in care could be influenced by factors not studied
here like comorbidities, adherence or duration on ART.
P003
Loss to follow-up of HIV-infected women after delivery:
The Swiss HIV Cohort Study and the Swiss Mother and
Child HIV Cohort Study
Karoline Aebi-Popp1; Roger Kouyos2; Barbara Bertisch3;
Cornelia Staehelin1; Irene Hoesli4; Martin Rickenbach5;
Claire Thorne6; Claudia Grawe7; Enos Bernasconi8;
Matthias Cavassini9; Begona Martinez de Tejada10; Marcel Stoeckle11;
Thanh Lecompte12; Christoph Rudin13 and Jan Fehr2
1
Department of Infectious Diseases, University Hospital Bern, Bern,
Switzerland. 2Department of Infectious Diseases, University Hospital
Zürich, Zürich, Switzerland. 3Department of Infectious Diseases,
Cantonal Hospital St. Gallen, St. Gallen, Switzerland. 4Department of
Obstetrics, University Hospital Basel, Basel, Switzerland. 5Data Centre
of the Swiss HIV Cohort Study, Institute for Social and Preventive
Medicine, Lausanne, Switzerland. 6UCL Institute of Child Health,
University College London, MRC Centre of Epidemiology for Child
Health, London, UK. 7Department of Obstetrics, University Hospital
Zürich, Zürich, Switzerland. 8Department of Infectious Diseases,
Cantonal Hospital Lugano, Lugano, Switzerland. 9Department of
Infectious Diseases, University Hospital Lausanne, Lausanne,
Switzerland. 10Department of Obstetrics, University Hospital Geneva,
Geneva, Switzerland. 11Department of Infectious Diseases, University
Hospital Basel, Basel, Switzerland. 12Department of Infectious
Diseases, University Hospital Geneva, Geneva, Switzerland.
13
Department of Nephrology, University Children’s Hospital, Basel,
Switzerland.
Introduction: HIV-infected pregnant women are very likely
to engage in HIV medical care to prevent transmission of
HIV to their newborn. After delivery, however, childcare and
31
competing commitments might lead to disengagement from
HIV care. The aim of this study was to quantify loss to followup (LTFU) from HIV care after delivery and to identify risk
factors for LTFU.
Methods: We used data on 719 pregnancies within the Swiss
HIV Cohort Study from 1996 to 2012 and with information on
follow-up visits available. Two LTFU events were defined: no
clinical visit for 180 days and no visit for 360 days in the
year after delivery. Logistic regression analysis was used to
identify risk factors for a LTFU event after delivery.
Results: Median maternal age at delivery was 32 years (IQR
2836), 357 (49%) women were black, 280 (39%) white, 56
(8%) Asian and 4% other ethnicities. One hundred and seven
(15%) women reported any history of IDU. The majority (524,
73%) of women received their HIV diagnosis before pregnancy, most of those (413, 79%) had lived with diagnosed HIV
longer than three years and two-thirds (342, 65%) were
already on antiretroviral therapy (ART) at time of conception.
Of the 181 women diagnosed during pregnancy by a
screening test, 80 (44%) were diagnosed in the first trimester,
67 (37%) in the second and 34 (19%) in the third trimester. Of
357 (69%) women who had been seen in HIV medical care
during three months before conception, 93% achieved an
undetectable HIV viral load (VL) at delivery. Of 62 (12%)
women with the last medical visit more than six months
before conception, only 72% achieved an undetectable VL
(p 0.001). Overall, 247 (34%) women were LTFU over 180
days in the year after delivery and 86 (12%) women were
LTFU over 360 days with 43 (50%) of those women returning.
Being LTFU for 180 days was significantly associated with
history of intravenous drug use (aOR 1.73, 95% CI 1.092.77,
p0.021) and not achieving an undetectable VL at delivery
(aOR 1.79, 95% CI 1.033.11, p 0.040) after adjusting for
maternal age, ethnicity, time of HIV diagnosis and being on
ART at conception.
Conclusions: Women with a history of IDU and women with a
detectable VL at delivery were more likely to be LTFU after
delivery. This is of concern regarding their own health, as well
as risk for sexual partners and subsequent pregnancies.
Further strategies should be developed to enhance retention
in medical care beyond pregnancy.
Poster Abstracts
Introduction: The costs of combination antiretroviral therapy
(cART) consisting of separate, particularly generic, components are generally much lower than of a single tablet
regimen (STR) including the same active ingredients. Our aim
was to evaluate whether patients in care in the Netherlands
would be willing to take separate component regimens (SCR)
instead of an STR and to examine whether willingness was
associated with particular patient characteristics.
Materials and Methods: Data from the HIV Monitoring
Foundation of all adult HIV-1-infected patients in care taking
cART 6 months were used to randomly select 1000 patients.
As part of a questionnaire developed for a study assessing
patient experience, patients were asked whether they were
willing to take an SCR instead of an STR. Logistic regression
was used to examine associations between age, gender,
region of origin, mode of HIV transmission, socioeconomic
status, duration of cART and answering ‘‘yes’’ to the question
versus ‘‘maybe’’ or ‘‘no.’’ Variables with pB0.1 in the
univariate analysis were entered in a multivariate model.
Results: Of the 300 patients who completed the questionnaire,
49% answered ‘‘yes,’’ 24% ‘‘maybe’’ and 27% ‘‘no’’ to the
question whether they would be willing to use a SCR. Reasons
for answering ‘‘no’’ included difficulties swallowing pills,
convenience of STR (especially when travelling/at work), and
concerns about side effects. Respondents who answered
‘‘maybe’’ often indicated that they preferred STRs, emphasized
the importance of taking the pills once daily, and pointed out
that efficacy/safety of an SCR should not be less. Having to pay
for medication was reported as a reason to consider switching
to an SCR. In the multivariate analysis, respondents who were
born outside the Netherlands were less likely; and those with
cART use ]15 yrs were more likely to answer ‘‘yes’’ (Table 1).
Conclusions: Half of the respondents were willing to take
SCRs instead of an STR. The likelihood of accepting to switch
to SCR seems less for migrants and for those who have
commenced treatment more recently. Duration of cART use
and region of origin may therefore be factors to take into
account when considering to prescribe SCR. Future studies
Abstract P004Table 1. Adjusteda odds ratios (OR), 95%
confidence intervals (95% CI) and p-values for respondents
(n300) reporting to be willing to use a separate component
regimen
P004
Patients’ willingness to take separate component
antiretroviral therapy regimens for HIV in the Netherlands
Characteristics
Esther Engelhard1,2; Colette Smith2; Sigrid Vervoort3; Frank Kroon4;
Kees Brinkman5; Pythia Nieuwkerk6; Peter Reiss1,2,7 and
Suzanne Geerlings1
1
Division of Infectious Diseases, Academic Medical Center, University
of Amsterdam, Amsterdam, Netherlands. 2Stichting HIV Monitoring,
Amsterdam, Netherlands. 3Department of Internal Medicine and
Infectious, University Medical Center, Utrecht, Netherlands.
4
Department of Infectious Diseases, Leiden University Medical
Center, Leiden, Netherlands. 5Department of Internal Medicine, Onze
Lieve Vrouwe Gasthuis, Amsterdam, Netherlands. 6Department of
Medical Psychology, Academic Medical Center, University of
Amsterdam, Amsterdam, Netherlands. 7AIGHD, Academic Medical
Center, University of Amsterdam, Amsterdam, Netherlands.
Region of origin
n (%)
OR (95%): ‘‘yes’’ vs.
‘‘maybe/no’’
p
Netherlands
234 (78)
Ref
Other
66 (22)
0.32 (0.160.64)
0.001
B5
510
78 (26)
88 (29)
Ref
1.73 (0.883.40)
0.110
1015
66 (22)
0.69 (0.331.46)
0.334
] 15
68 (23)
3.18 (1.496.79)
0.003
Duration of cART
use (yrs)
a
Adjusted for age, gender, mode of transmission and socioeconomic
status.
32
should investigate whether an expressed willingness to
switch will translate into maintained high levels of adherence
and viral suppression.
P005
Real-world medication persistence with single versus
multiple tablet regimens for HIV-1 treatment
Donna Sweet1; Jinlin Song2; Yichen Zhong2 and James Signorovitch2
1
Internal Medicine, The University of Kansas School of Medicine Wichita, Wichita, KS, USA. 2Health Economics and Outcomes
Research, Analysis Group Inc., Boston, MA, USA.
Poster Abstracts
Introduction: Adherence to antiretroviral (ARV) treatment
for HIV-1 is crucial to achieving optimal clinical outcomes.
Simplification of regimens with once-daily single-tablet regimens (STRs) can improve adherence compared to multi-tablet
regimens (MTRs). This study compared real-world persistence
(a proxy for treatment effectiveness and adherence) between
HIV-1 infected patients receiving STRs versus MTRs.
Materials and Methods: Adult HIV-1 infected patients starting
their first observed ARV regimen (with at least six prior
months of no ARV treatment) were identified in the MarketScan claims database (10/200803/2014). Persistence was
measured as the time from the index regimen start date to
Abstract P005Figure 1. Persistence on ARV regimens among HIV-1 infected patients.
Abstract P005Figure 2. Comparison of persistence on ARV regimens among patients treated with EVG/COBI/TDF/FTC, RPV/TDF/FTC, EFV/
TDF/FTC and MTR (after EVG/COBI/TDF/FTC became available on August 27, 2012).
33
Poster Abstracts
Abstract P005Table 1. Comparison of treatment persistence between patients treated with STRs versus MTRs
Comparison
Unadjusted HR
Unadjusted
Adjusted HR
Adjusted
(95% CI)
P
(95% CI)
P
0.53 (0.49, 0.57)
B.0001
0.54 (0.50, 0.58)
B.0001
0.56 (0.52, 0.60)
B.0001
0.58 (0.53, 0.62)
B.0001
Comparison of STR vs MTR
STR vs MTR
Pairwise comparisons of specific STRs with each other and with MTR
EFV/TDF/FTC vs MTR
Sample restricted to patients with index date after RPV/TDF/FTC became
available on August 10, 2011
RPV/TDF/FTC vs EFV/TDF/FTC
0.67 (0.53, 0.85)
0.0009
0.66 (0.52, 0.84)
0.0007
RPV/TDF/FTC vs MTR
0.40 (0.32, 0.51)
B.0001
0.41 (0.32, 0.52)
B.0001
B.0001
Sample restricted to patients with index date after EVG/COBI/TDF/FTC became
available on August 27, 2012
EVG/COBI/TDF/FTC vs EFV/TDF/FTC
0.46 (0.34, 0.61)
B.0001
0.45 (0.34, 0.60)
EVG/COBI/TDF/FTC vs RPV/TDF/FTC
0.93 (0.60, 1.43)
0.7351
0.95 (0.61, 1.48)
0.8284
EVG/COBI/TDF/FTC vs MTR
0.30 (0.22, 0.40)
B.0001
0.31 (0.23, 0.42)
B.0001
the end of the first 90-day gap between fills for any ARV in the
index regimen, or to the start date of an ARV not in the index
regimen. Persistence was described using KaplanMeier
curves and compared using log-rank tests, and Cox proportional hazards models adjusted for age, gender, insurance
type, region, employment status, Charlson Comorbidity Index,
other comorbidities, hospitalizations, emergency room visits
and office visits. STRs were further stratified by regimen.
Results: A total of 3257 patients (37%) initiated MTRs, and
5484 (63%) initiated STRs, including 4409 on efavirenz (EFV)/
tenofovir (TDF)/emtricitabine (FTC), 484 on rilpivirine (RPV)/
TDF/FTC, and 591 on elvitegravir (EVG)/cobicistat (COBI)/TDF/
FTC. Median persistence was 45.0 months for STRs versus
15.2 months for MTRs (P B0.001; Figure 1). Median persistence was not reached for RPV/TDF/FTC or EVG/COBI/TDF/
FTC; 31 months after RPV/TDF/FTC approval for the treatment
of HIV-1 infection, more than 65% of patients who started on
it remained persistent, and 19 months after EVG/COBI/TDF/
FTC approval, more than 72% of patients who started on it
remained persistent. Compared with MTRs, STRs had an
approximately 50% lower hazard of discontinuation (adjusted
hazard ratio [HR] 0.54, 95% CI 0.500.58). EVG/COBI/TDF/
FTC and RPV/TDF/FTC had significantly longer unadjusted and
adjusted persistence compared with EFV/TDF/FTC (Figure 2,
Table 1).
Conclusions: Among HIV-1 infected patients, the use of STRs
was associated with longer regimen persistence compared
with MTRs. Among STRs, EVG/COBI/TDF/FTC and RPV/TDF/
FTC were associated with significantly longer persistence
than EFV/TDF/FTC.
P006
No difference in persistence to treatment with atazanavir or
darunavir in HIV patients in a real-world setting
Amanda M Farr1; Stephen S Johnston2; Corey Ritchings3;
Matthew Brouillette1 and Lisa Rosenblatt4
1
Life Sciences, Truven Health Analytics, Cambridge, MA, USA. 2Life
Sciences, Truven Health Analytics, Bethesda, MD, USA. 3US Medical
HIV, Bristol-Myers Squibb, Princeton, NJ, USA. 4Health Economics and
Outcomes Research, Bristol-Myers Squibb, Plainsboro, NJ, USA.
Introduction: There is a lack of data comparing the protease
inhibitors (PIs) atazanavir (ATV) and darunavir (DRV) in a realworld setting.This study compared persistence (time to switch/
discontinuation) to therapy between ATV-treated and DRVtreated patients with human immunodeficiency virus (HIV).
Materials and Methods: Retrospective, observational cohort
study using US insurance claims for commercially and Medicaidinsured patients. Patients were aged ]18 years and initiated
an ATV- or DRV-based regimen boosted with ritonavir between
7/1/2006 and 3/31/2013, with ]6 months of continuous
enrolment prior to and ]3 months of continuous enrolment
following initiation; patients were required to have ]1
inpatient or outpatient medical claim with an ICD-9-CM
diagnosis code for HIV during that time period of enrolment.
Patients with no claims for antiretroviral therapy (ART) any
time prior to initiation were considered to be ART-naı̈ve. Time
to switch/discontinuation was defined as the number of days
from initiation of the regimen until earliest of: (1) a ]30-day
continuous gap in therapy in ATV or DRV; (2) a prescription
claim for an ART agent that was not part of the initial regimen
(with the exception of changes in concomitant nucleoside
reverse transcriptase inhibitors or the addition of integrase
inhibitors); (3) censoring at a ]30-day continuous gap in
therapy in ritonavir; (4) censoring at disenrolment from
insurance benefits or (5) censoring at the study end date
(9/30/2013 in the commercial data and 12/31/2013 in the
Medicaid data). Time to switch/discontinuation was compared
using incidence rates and multivariable Cox proportional
hazards models adjusted for calendar time, patient demographics and clinical characteristics.
34
Poster Abstracts
Abstract P006Table 1. Incidence and adjusted hazard ratio of switch/discontinuation among patients with HIV initiating an ATV- or
DRV-based ART regimen
Incidence of switch/discontinuation
Adjusted hazard ratio of switch/
per 100 person-years
discontinuation atazanavir vs darunavir
p-value for adjusted
(95% confidence interval)
(95% confidence interval)
hazard ratio
ATV (N 1581)
48.3 (45.351.5)
1.119 (0.9661.295)
0.134
DRV (N 859)
47.1 (42.851.8)
Reference
Commercially insured
patients: ART-naı̈ve
Commercially insured
patients: ARTexperienced
ATV (N1151)
42.7 (39.546.1)
1.091 (0.9611.238)
39.2 (35.343.6)
Reference
ATV (N 1276)
90.0 (84.496.1)
1.120 (0.9651.300)
DRV (N 419)
87.3 (77.498.5)
Reference
ATV (N 895)
84.9 (78.491.8)
0.929 (0.7791.109)
DRV (N 377)
84.2 (74.395.5)
Reference
DRV (N 712)
Medicaid-insured patients:
0.177
ART-naı̈ve
0.135
Medicaid-insured patients:
ART-experienced
0.416
ATV atazanavir; DRV darunavir; ART antiretroviral therapy.
Results: Table 1 displays the study results and cohort
sample sizes. Mean ages across the cohorts were 4142
years. The proportions of patients who were ART-naı̈ve were
5859% among the ATV/r cohorts and 5355% among
the DRV/r cohorts. There were no significant differences in
the adjusted hazards of switch/discontinuation between the
cohorts.
Conclusions: The incidence of switch/discontinuation was
higher among Medicaid patients (who may be socioeconomically disadvantaged) than Commercial patients. There were no
significant differences in persistence (time to switch/discontinuation) with the initiated PI among HIV patients who initiated
an ATV-based regimen versus a DRV-based regimen.
P007
Abstract Withdrawn
35
P008
Patient preferences for characteristics of antiretroviral
therapies: results from five European countries
Brian Gazzard1; Shehzad Ali2; Axel Muhlbacher3; Neda Ghafouri4;
Franco Maggiolo5; Catherine Golics6; Silvia Nozza7; Maria Jose
Fuster8; Antonio Antela9; Jean Jacques Parienti10; Nathalie Dang11;
Sylvie Ronot Bregigeon12; Andrew Benzie13 and Miranda Murray14
1
HIV and Sexual Health, Chelsea & Westminster, London, UK. 2Health
Economics, ICON plc, Oxford, UK. 3Economics, IGM Institute of
Management, Neubrandenburg, Germany. 4Medical Affairs, ViiV
Healthcare, Munich, Germany. 5Antiviral Therapy Unit, Bergamo,
Italy. 6Patient Reported Outcomes, ICON plc, Oxford, UK. 7Vaccine
and Immunotherapy Research, IRCCS, San Raffaele, Italy. 8SEISIDA,
Madrid, Spain. 9H. Conxo, S de Compostela, Spain. 10Biostatistics and
Results
Odds ratio*
(95% Confidence
Variables (reference category)
Interval)
Viral load (reference: undetectable)
400 copies/mL in 4 weeks,
0.87 (0.830.91)
undetectable after 3 months
1000 copies/mL in 4 weeks,
0.78 (0.740.81)
undetectable after 3 months
CD4 cell count (reference: increase of
CD4 100 m3)
Increase of CD4 50/mm3 after
0.91 (0.870.95)
3 months
Increase of CD4 25/mm3 after
0.86 (0.820.89)
3 months
Diarrhoea (reference: no diarrhoea)
3 episodes of diarrhoea/day
0.71 (0.680.74)
6 episodes of diarrhoea/day
0.36 (0.330.38)
Long-term health problems (reference:
no increased risk)
10% risk of future health problems
0.55 (0.530.57)
20% risk of future health problems
0.30 (0.280.32)
Treatment failure (reference: all ARTs
available)
0.79 (0.750.82)
Some ARTs can’t be used; others
0.70 (0.670.73)
only partially effective
requirements)
0.93 (0.890.97)
0.80 (0.760.83)
drug interactions)
ART dosage adjusted; may increase
0.75 (0.720.79)
risk of side effects
Cannot take certain medications
Introduction: Patient preference to antiretroviral therapy
(ART) characteristics should be a key consideration in
treatment decisions. ART options exist for people living with
HIV (PLWH), however concerns remain related to PLWH
satisfaction with current ARTs. The current study examines
patient preferences and the strength of preferences for
treatment characteristics associated with ART.
Materials and Methods: Patients’ preferences to ART were
explored using a discrete choice experiment (DCE). Seven
defined treatment characteristics (each with three categories)
were identified from a literature review, input from experts,
PLWH and physicians. A total of 1582 PLWH from France,
Germany, Spain, Italy and the UK were recruited for the study.
An adjusted odds ratio B1 signified lower odds of selecting a
treatment with this characteristic category, compared to the
reference category, independently of other characteristics.
Results: The patient preference analyses showed that participants preferred treatments with a rapid reduction in viral
load (OR 0.78; 95% CI 0.740.81) and CD4 count (OR 0.86; 95% CI0.820.89). Participants had a strong preference for avoiding diarrhoea (Odds ratio, OR0.36 95%
CI0.330.38) and long term health problems (OR 0.30,
95% CI0.280.32). Convenience related issues related to
restrictions on taking drugs because of food or drug interactions were important to avoid (OR 0.80, 95% CI 0.76
0.83 and OR0.72 95% CI0.690.76 respectively). Participants also had a strong preference to avoid drugs which
limited the effectiveness of future treatments (OR 0.70,
95% CI0.670.73).
Conclusions: Avoidance of diarrhoea and long-term complications were the most important drivers of patient choice.
This study, from a large sample of European patients, demonstrates the importance to patients when different aspects of
HIV treatment are considered simultaneously.
P010
Rates of cardiovascular events and deaths are associated
with advanced stages of HIV-infection: results of the HIV
HEART study 7, 5 year follow-up
Food restrictions (reference: no food
ARTs on empty stomach
Drug-drug interactions (reference: no
Clinical Research, Faculte de Medecine de Caen, Caen, France.
Medical Affairs, ViiV Healthcare, Singapore, Singapore.
12
Immunology and Hematology, CHU Sainte Marguerite, Marseille,
France. 13Medical Affairs, ViiV Healthcare, London, UK. 14Health
Outcomes, ViiV Healthcare, London, UK.
11
ADVERSE EVENTS CARDIOVASCULAR
ARTs only partially effective
ARTs with food
Poster Abstracts
0.72 (0.690.76)
*The results indicated significant p-valuesB0.05 for each variable.
Stefan Esser1; Lewin Eisele2; Birte Schwarz3; Christina Schulze3;
Volker Holzendorf4; Nobert H. Brockmeyer5; Martin Hower6;
Friedhelm Kwirant7; Roland Rudolph8; Till Neumann3 and
Nico Reinsch3
1
Dermatology and Venerology, University Hospital Essen, Essen,
Germany. 2Institute for Medical Informatics, University Hospital
Essen, Essen, Germany. 3Cardiology, University Hospital Essen, Essen,
Germany. 4Clinical Trial Centre Leipzig, University Leipzig, Leipzig,
Germany. 5Department of Dermatology and Venerology, University
Hospital Bochum, Bochum, Germany. 6Internal Medicine, City
36
Hospital Dortmund, Dortmund, Germany. 7General Practice, HIVMedicine, Duisburg, Germany. 8HIV-Medicine, Outpatient-Clinic of
Oncology, Essen, Germany.
Introduction: Cardiovascular diseases are increasing in
aging HIV-positive patients (HIV). Impact of traditional
cardiovascular risk factors, HIV-specific parameters and
antiretroviral therapy (ART) on the incidence of cardiovascular events (CVE) and on the mortality rate are investigated
in different HIV cohorts.
Methods: The HIV HEART (HIVH) study is an ongoing
prospective observational cohort study in the German Ruhr
area to assess the frequency and clinical course of cardiac
disorders in 1481 HIV by standardized non-invasive cardiovascular screening. CVE were defined as diagnosed or
documented myocardial infarction, coronary heart disease,
arterial coronary intervention, stent implantation, bypass
operation and stroke.
Results: 1481 HIV subjects (mean age: 49.3910.7 years (y),
female: 15.6%) were included. 130 CVE and 90 deaths were
documented until the end of 7, 5 year follow-up of HIVH.
Mean duration of the HIV-infection was 12.996.8 y. HIV
were treated with ART on average for 8.696.8 y. According
to the CDC classification of the HIV-infection, HIV were
distributed over the clinical categories (A:34.6%; B:31.4%
and C:33.9%) while more than the half had an advanced
Poster Abstracts
immunodeficiency (I:8.3%; II:41.1%; III:50.7%). Advanced
clinical and immunological stages were significantly (pB0.001)
associated with higher incidences of deaths (A:16.7%; B:26.7%;
C:56.7% and I:6.7%; II:27.7%; III:65.6%) and CVE (A:17.7%;
B:33.1%; C:49.2% and I:3.1%; II:32.3%; III:64.6%) but not with
the duration of HIV-infection (per y: Hazard ratio (HR): 0.91
[0.880.94]) and ART (per y: HR: 0.81 [0.790.84]) adjusted
for age. The proportion of deceased HIV with HIV-RNA
]50 copies/mL and lower CD4-cell counts at their last visit
is significantly higher compared with living HIV without
CVE (HIV-RNA ]50 copies/mL: 25.6% vs 14.7%). Median
CD4-cells: 286.5 cells/mL (IQR: 168.8482.8) versus 574 cells/
mL (IQR: 406786). 96.1% of the living HIV with CVE had
HIV-RNAB50 copies/mL and median CD4-cells 542.5 cells/mL
(IQR: 370793.5).
Conclusions: Advanced clinical and immunological stages of
HIV-infection, but not the duration of ART, were associated
with higher incidences of CVE and deaths in the HIVH cohort.
These observations support an earlier initiation of ART in
HIV. Special cardiovascular risk calculations for HIV should
consider immunological and clinical categories of the HIVinfection.
P011
Abstract Withdrawn
37
P012
Comparison of oxidative stress markers in HIV-infected
patients on efavirenz or atazanavir/ritonavir-based therapy
Vicente Estrada1; Susana Monge2; Dulcenombre Gómez-Garre3;
Paz Sobrino2; Juan Berenguer4; Jose Ignacio Bernardino5;
Jesús Santos6; Ana Moreno Zamora7; Esteban Martı́nez8 and
Jose Ramón Blanco9
1
Infectious Diseases, Hospital Clinico San Carlos, Madrid, Spain.
2
Instituto de Salud Carlos III, Centro Nacional de Epidemiologı́a,
Madrid, Spain. 3Vascular Biology Lab, Hospital Clinico San Carlos,
Madrid, Spain. 4Infectious Diseases, Hospital General Gregorio
Marañón, Madrid, Spain. 5Infectious Diseases, Hospital La Paz,
Madrid, Spain. 6Infectious Diseases, Hospital Virgen de la Victoria,
Malaga, Spain. 7Infectious Diseases, Hospital Ramon y Cajal, Madrid,
Spain. 8Infectious Diseases, Hospital Clinic, Barcelona, Spain.
9
Infectious Diseases, Hospital San Pedro-CIBIR, Logroño, Spain.
Introduction: Chronic low-grade inflammation and immune
activation may persist in HIV patients despite effective
antiretroviral therapy (ART). These abnormalities are associated with increased oxidative stress (OS). Bilirubin (BR) may
have a beneficial role in counteracting OS. Atazanavir (ATV)
inhibits UGT1A1, thus increasing unconjugated BR levels, a
distinctive feature of this drug. We compared changes in OS
markers in HIV patients on ATV/r versus efavirenz (EFV)-based
first-line therapies.
Materials and Methods: Cohort of the Spanish Research
Network (CoRIS) is a multicentre, open, prospective cohort of
HIV-infected patients naı̈ve to ART at entry and linked to a
biobank. We identified hepatitis C virus/hepatitis B virus (HCV/
HBV) negative patients who started first-line ART with either
ATV/r or EFV, had a baseline biobank sample and a followup sample after at least nine months of ART while maintaining initial regimen and being virologically suppressed.
Lipoprotein-associated Phospholipase A2 (Lp-PLA2), Myeloperoxidase (MPO) and Oxidized LDL (OxLDL) were measured in
paired samples. Marker values at one year were interpolated
from available data. Multiple imputations using chained
equations were used to deal with missing values. Change in
the OS markers was modelled using multiple linear regressions adjusting for baseline marker values and baseline confounders. Correlations between continuous variables were
explored using Pearson’s correlation tests.
Results: 145 patients (97 EFV; 48 ATV/r) were studied. Mean
(SD) baseline values for OS markers in EFV and ATV/r groups
Poster Abstracts
were: Lp-PLA2 [142.2 (72.8) and 150.1 (92.8) ng/mL], MPO
[74.3 (48.2) and 93.9 (64.3) mg/L] and OxLDL [76.3 (52.3) and
82.2 (54.4) mg/L]. After adjustment for baseline variables
patients on ATV/r had a significant decrease in Lp-PLA2
(estimated difference 16.3 [CI 95%: 31.4, 1.25; p
0.03]) and a significantly lower increase in OxLDL (estimated
difference 21.8 [38.0, 5.6; p B0.01] relative to those
on EFV, whereas no differences in MPO were found. Adjusted
changes in BR were significantly higher for the ATV/r group
(estimated difference 1.33 [1.03, 1.52; pB0.01]). Changes in
BR and changes in OS markers were significantly correlated.
Conclusions: In virologically suppressed patients on stable
ART, OS was lower in ATV/r-based regimens compared to EFV.
We hypothesize these changes could be in part attributable
to increased BR plasma levels.
P013
Epi-aortic lesions, pathologic FMD, endothelial activation
and inflammatory markers in advanced naı̈ve HIV-infected
patients starting ART therapy
Chiara Bellacosa1; Paolo Maggi1; Anna Volpe1; Sergio Altizio1;
Nicoletta Ladisa1; Silvia Cicalini2; Rosaria Viglietti3;
Antonio Chirianni3; Lara Bellazzi4; Domenico Zanaboni4;
Renato Maserati4; Canio Martinelli5; Paola Corsi5; Silvia Sofia6;
Maurizio Celesia6; Ferdinando Sozio7; Nicola Abbrescia8 and
Gioacchino Angarano1
1
Clinical Infectious Diseases, University of Bari, Policlinico
Consorziale, Bari, Italy. 2INMI L. Spallanzani, IRCCS Roma, Roma,
Italy. 3Clinical Infectious Diseases, Ospedale Cotugno Napoli, Napoli,
Italy. 4Clinical Infectious Diseases, Policlinico San Matteo, Pavia, Italy.
5
Clinical Infectious Diseases, Ospedale Careggi, Firenze, Italy. 6Clinical
Infectious Diseases, Ospedale Garibaldi-Nesima, Catania, Italy.
7
Clinical Infectious Diseases, Ospedale Civile Spirito Santo, Pescara,
Italy. 8IV Clinical Infectious Diseases, Ospedale Cotugno, Napoli,
Italy.
Introduction: PREVALEAT II (PREmature VAscular LEsions and
Antiretroviral Therapy II) is an ongoing multicenter, longitudinal cohort study aimed to the evaluation of cardiovascular (CV) risk in advanced HIV-infected antiretroviral (ARV)
naı̈ve patients starting their first antiretroviral therapy
(ART).
Patients and methods: All consecutive naı̈ve patients with
CD4 cell countB200/mL starting any PI/r-based or NNRTI-
38
Poster Abstracts
Percentage of patients with pathologic values
Baseline
T1
T1
T2
T2
T3
T3
%
%
p
%
p
%
p
EPI-aortic lesions
48.78
36.78
0.93
48.80
0.34
62.79
0.42
Pathologic FMD
ICAM-1
34.54
75.32
38.89
72.89
0.78
0.27
31.43
85.10
0.82
0.1943
26.09
92.86
0.59
0.018
VCAM-1
85.71
78.44
0.26
87.23
0.8113
95.24
0.111
IL-6
37.66
50
0.16
40.42
0.75
21.43
0.06
D-dimers
55.84
26.7
0.0009*
19.15
B0.0001*
16.67
B0.0001*
HS-CRP
37.66
22.22
0.116
19.15
0.09
16.67
0.017*
9.64
30.43
0.001*
33.82
0.0001*
41.86
B0.00001*
HDLC
71.08
52.1
0.16
51.67
0.18
44.19
0.0032*
LDLC
Triglycerides
2.4
33.73
7.25
46.30
0.16
0.11
8.62
46.03
0.09
0.13
2.33
37.21
0.98
0.71
Glycaemia
18.07
21.74
0.57
7.94
0.08
11.63
0.35
Total cholesterol
% percentage of patients; p statistical values; * statistically significant.
based 2 NRTIs regimen from January 2010 to January
2013 in the participant centres were enrolled. At baseline
and after 3 (T1), 6 (T2) and 12 (T3) months patients were
subjected to epi-aortic vessels ultrasonography and brachial
artery flow mediated dilation (FMD). Viral load, CD4 cell
count, serum lipid values, serum glucose, endothelial
activation (ICAM-1 and VCAM-1) and inflammatory markers
(IL-6 and hsCRP) values were recorded at the same time.
Data about independent risk factors for HIV infection and
CV disease are taken at time 0. We enrolled 94 patients:
81% males, 87% caucasians, 40% smokers, 8.2% HCV coinfected and 3.5% with lipodystrophy; 33% of them were
homosexuals, 12% drug addicts; 23% were AIDS at presentation. Statistical data analysis has been conducted by
the x2 nonparametric method.
Results: In Table 1 it is reported the percentage of patients
with pathologic values, moreover, at T3, 60.46% showed
undetectable viraemia and 69.77% had CD4 200.
Conclusions: Our data evidence at baseline has a relevant
deterioration of CV conditions in terms of ultrasonographic data, FMD, inflammation and cytokine markers
among advanced naı̈ves. During follow-up epi-aortic lesions
tend to worsen but not significantly, percentage of pathologic FMD remains stable. Regarding markers of endothelial
activation ICAM-1 significantly worsens during the period
of observation; also VCAM-1 has a trend towards the
worsening while not significantly. Conversely, a significant
improvement was observed for the markers of inflammation D-dimers and high sensitivity C-reactive protein
(hsCRP). IL-6 improved but not significantly. Serum lipid
profile shows an increase of HDLc and total cholesterol, but
not of LDLc. In conclusion, after a twelve-month follow-up
period, CV risk of the patients remains high. ARV therapy
seems in fact to improve only non-specific and poor sensitive
inflammation biomarkers and HDLc; markers of endothelial
activations tend to worsen, intima-media ultrasonography
and FMD do not show relevant modifications. Further data
are warranted to better understand the role of the different
ARV regimens.
P014
Effectiveness of a team intervention in reducing modifiable
cardiovascular disease risk in HIV-infected subjects on
antiretroviral therapy
Mark Bloch; Avindra Jayewardene; Trina Vincent; Natalie Linton;
Dick Quan and Andrew Gowers
Clinical Research Department, Holdsworth House Medical Practice,
Darlinghurst, Australia.
Introduction: The increasing age, higher modifiable and
inherent cardiovascular disease (CVD) risk of HIV-infected
patients [1] necessitates improved approaches to reducing
co-morbidities. We aimed to assess the effectiveness of a
team intervention in reducing modifiable CVD risk.
Materials and Methods: HIV-infected patients ]50 years
attending a large HIV caseload primary-care practice, who were
virologically suppressed on antiretroviral therapy (ART), with
moderate or severe 10-year CVD Framingham risk ( ]10%)
were recruited for this prospective case-control study. Intervention participants were provided a team approach to care,
which involved treatment by study doctors for lipid, hypertension and ART management, and monthly review by a team of
research nurses and dieticians for smoking cessation, exercise
and dietary advice over 12 months. Controls were matched on
age and smoking status, and were given standard of care (SOC)
by non-study doctors. Outcomes included CVD risk factors,
body composition and CVD risk assessment, including Framingham 10-yr risk [2] and D:A:D 5-year estimated risk of
coronary heart disease (CHD) [3]. Repeated measures analysis
of variance was used to examine pre- and post-intervention
39
Poster Abstracts
Descriptive characteristics of participants at baseline and the change over the 12-month study
Intervention
Control
Intervention D from
Control D from
P
P
Variable
Baseline
Baseline
baseline
baseline
(t effect)
(g t interaction)
Framingham 10-year risk (%)
19.696.6
21.298.9
3.495.7
0.395.9
0.013
0.033
D:A:D 5-year risk (%)
6.495.9
5.494.9
1.493.1
0.693.3
NS
0.017
Total cholesterol (mmol/L)
5.291.0
4.991.1
0.690.9
0.090.9
0.011
0.013
High-density lipoprotein
1.290.3
1.290.3
0.590.2
0.190.3
NS
NS
Systolic blood pressure
(mmHg)
130913
132912
6.2917.1
0.6912.4
NS
NS
% Body fat
22.394.2
1.091.9
0.009
-
(mmol/L)
Descriptive characteristics of participants at baseline and the change over the 12-month study programme. Mean9SD; NS, not significant.
differences, with p-values used to assess time and main effects
of approach to care (Intervention, SOC).
Results: A total of 33 patients completed the intervention,
with 33 controls (58.096.8 and 59.196.9 years, respectively). Smoking cessation occurred in 25% cases versus nil
controls. There was a significant change in CVD risk between
intervention and control groups, in both Framingham scores
(time and group time interaction) and D:A:D scores
(group time interaction only) (Table 1). There was also a
significant difference in change in total cholesterol over
the study period (time and group time interaction). Body
composition was only measured in intervention patients,
with a significant loss in % body fat observed in pre- and
post-intervention.
Conclusions: Team intervention was significantly more effective than standard of care in reducing CVD risk in HIVinfected patients on ART. A team approach to care may
be an important component of reducing CVD risk in this
population.
References
1. Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute
myocardial infarction rates and cardiovascular risk factors among
patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007;92(7):250612.
2. Anderson KM, Odell PM, Wilson PW, Kannel WB. Cardiovascular
disease risk profiles. Am Heart J. 1991;121(1 Pt2):2938.
3. Friis-Möller N, Sabin CA, Weber R, d’Arminio Monforte A, El-Sadr
WM, Reiss P, et al. Combination antiretroviral therapy and the
risk of myocardial infarction. N Engl J Med. 2003 Nov 20;349(21):
19932003.
P015
Evolution of Framingham cardiovascular risk score in HIVinfected patients initiating EFV- and LPV/r-based HAART in a
Latin American cohort
Diego Cecchini1; Maria Ines Mattioli1; Julia Cassetti2; Debora Chan3
and Isabel Cassetti1
1
Helios Salud, Area Medica, Buenos Aires, Argentina. 2Instituto de
Desarrollo Humano, Universidad Nacional de General Sarmiento,
Buenos Aires, Argentina. 3Facultad Regional Buenos Aires,
Departamento de Matemática, Universidad Tecnológica Nacional,
Buenos Aires, Argentina.
Introduction: Epidemiological studies suggest that some antiretroviral drugs may contribute to increase cardiovascular risk
in HIV-infected patients. However, data from Latin American
countries are limited, as impact of HAARTon cardiovascular risk
remains understudied. In this context, we aimed to evaluate if
10-year Framingham Cardiovascular Risk Score (FCRS) increases in patients following exposure to EFV- and LPV/r-based
HAART in a Latin American cohort.
Materials and Methods: Retrospective 48-week cohort study.
We reviewed clinical charts of randomly selected samples of
patients initiating (according to national guidelines) EFV firstline HAART and LPV/r first- or second-line (but first PI-based)
HAART assisted at a reference HIV centre in Buenos Aires,
Argentina (period 20042012). Each patient could only be
included in one arm. FCRS was calculated according to
National Institutes of Health risk assessment tool (http://
cvdrisk.nhlbi.nih.gov/).
Results: A total of 357 patients were included: 249 in EFV arm
and 108 in LPV/r arm (80 as first line and 28 as second line,
but first PI-based HAART). Baseline characteristics (median,
interquartile range): age, 38 (3345) years; male, 247 (69%);
viral load, 98200 (20550306000) copies/mL; CD4 T-cell
count, 115 (60175) cel/mL; total cholesterol, 159 (135
194) mg/dL; HDL: 39 (3141) mg/dL; LDL: 94 (72123) mg/
dL; current smoker, 29%; on antihypertensive drugs: 14 (4%),
diabetic: 4 (1%). Most frequent accompanying nucleoside
reverse transcriptase inhibitors (NRTIs) were 3TC (92%) and
zidovudine (AZT; 76%). Baseline FCRS was low, moderate and
high for 93%, 7% and 0% of patients on EFV arm and 96.7%,
1.7% and 1.7% on LPV/r arm. On EFV arm, an increase in FCRS
category (low to moderate or moderate to high) was
observed in 1 patient (0.9%) at 24 weeks and 6 (5,6%) at
48 weeks; 5 (4.7%) decreased category. On LPV/r arm no one
varied FCRS category at 24 weeks and 2 (3.4%) increased
from low to moderate at 48 weeks (no patient decreased
FCRS category). Cumulative incidence of overall cardiovascular events was 1.6% on EFV and 1.8% on LPV/r arms
respectively. Probability of increasing FCRS category or having
a cardiovascular event did not differ between arms at a
significance level of 5%.
40
Conclusion: Probability of increasing FCRS category and
cardiovascular events was low and similar in patients exposed
to EFV versus LPV/r-based HAART in a Latin American cohort.
ClinicalTrials.gov Identifier: NCT01705873.
References
1. The DAD Study Group. Class of Antiretroviral Drugs and the Risk of
Myocardial Infarction. N Engl J Med 2007;356:172335.
2. Friis-Møller N, Smieja M, Klein D. Antiretroviral therapy as
a cardiovascular disease risk factor: fact or fiction? A review of
clinical and surrogate outcome studies. Curr Opin HIV AIDS.
2008;3:2205.
3. Magenta L, Dell-Kuster S, Richter W, et al. Lipid and Lipoprotein
Profile in HIV-Infected Patients Treated with Lopinavir/Ritonavir as a
Component of the First Combination Antiretroviral Therapy. AIDS
Research and Human Retroviruses. 2011;27:52533.
P016
Cardiovascular markers of inflammation and serum lipid
levels in HIV-infected patients with undetectable viraemia
Klaudija Viskovic1; Snjezana Zidovec-Lepej2; Lana Gorenec2;
Ivana Grgic2; Davorka Lukas3; Sime Zekan3; Anja Dragobratovic3 and
Josip Begovac3
1
Radiology and Ultrasound, University Hospital for Infectious
Diseases, Zagreb, Croatia. 2Department of Molecular Diagnostics and
Flow Cytometry, University Hospital for Infectious Diseases, Zagreb,
Croatia. 3Reference Center for Diagnostics and Treatment of, Zagreb,
University Hospital for Infectious Diseases, Croatia.
Introduction: Successfully treated HIV-infected patients may
still have an increased risk for cardiovascular morbidity and
mortality, which might be related not only to traditional risks,
but also to inflammation and dyslipidemia induced by HIV
and/or antiretroviral therapy [1,2]. We examined the relationship of serum lipid levels with plasma biomarkers of
inflammation using a composite inflammatory burden score
(IBS) from the following seven markers of inflammation:
CD40L, tPA, MCP-1, IL-8, IL-6, hCRP and P-selectin.
Materials and Methods: Subjects were selected among
consecutive HIV-infected males ]18 years of age with an
undetectable viral load ( B50 copies/mL of HIV1-RNA), seen
at the University Hospital for Infectious Diseases, Zagreb,
Croatia, in the period from January 2012 to March 2013.
Plasma inflammatory biomarkers (CD40L, tPA, MCP-1, IL-8, IL6, hCRP and P-selectin, quantified by bead-based cytometry)
75th percentile were considered elevated and an IBS was
constructed as the presence of zero, one, two, or three or
more elevated biomarkers. Correlations between the IBS and
lipid parameters were examined using Spearman’s Rho and
by ordered logistic regression proportional odds model to
estimate the odds of more elevated (75th percentile)
biomarkers.
Results: 181 male patients were included into the study, the
median age was 46.7 (Q1Q3, 39.955.0) years and the
median current CD4 cell count was 553.0 (Q1Q3, 389729)
per microliter. The patients were mainly treated with two
nucleoside reverse transcriptase inhibitor (NRTI) plus one
non-NRTI (NNRTI) (N100, 60.8%) or two NRTI plus lopinavir
(N 50, 27.6%). There was a significant correlation between
the IBS and serum cholesterol (Rho 0.23, 95% CI, 0.09
Poster Abstracts
0.37), triglycerides (Rho 0.30, 95% CI, 0.160.42) and
cholesterol/HDL-cholesterol ratio (Rho 0.25, 95% CI 0.11
0.38). In the multivariable model a one unit increase in
cholesterol/HDL-cholesterol ratio was associated with a 1.72fold (95% CI, 1.272.33) increased odds of having a greater
IBS. One unit increase (mmol/L) of cholesterol and triglycerides was associated with a 1.41-fold (95% CI, 1.131.76) and
1.37-fold (95% CI, 1.181.60) increased odds of having a
greater IBS, respectively.
Conclusions: Our study suggests that in virologically suppressed patients there is a significant association between
markers of inflammation and serum levels of cholesterol and
triglycerides as well as the cholesterol/HDL-cholesterol ratio.
References
1. Currier JS, Taylor A, Boyd F, et al. Coronary heart disease in
HIV-infected individuals. J Acquir Immune Defic Syndr. 2003;33(4):
50612.
2. Martinez E, D’Albuquerque PM, Llibre JM, et al. Changes in
cardiovascular biomarkers in HIV-infected patients switching from
ritonavir-boosted protease inhibitors to raltegravir. AIDS. 2012;26
(18):231526.
P017
Prevalence and concordance of high cardiovascular disease
scores in HIV/AIDS patients from Croatia and Serbia with
four international algorithms
Josip Begovac1; Gordana Dragovic2; Klaudija Viskovic1; Jovana Kusic3;
Marta Perovic Mihanovic 1; Davorka Lukas1 and Djordje Jevtovic3
1
Department of Infectious Diseases, University Hospital for Infectious
Diseases, Zagreb, Croatia. 2Department of Pharmacology and Clinical
Pharmacology, School of Medicine, University of Belgrade, Belgrade,
Serbia and Montenegro. 3HIV/AIDS Unit, Institute for Infectious and
Tropical Diseases, Belgrade, Serbia and Montenegro.
Introduction: We evaluated cardiovascular risks in HIVinfected patients from Croatia and Serbia and the eligibility
for statin therapy as recommended by the 2013 American
College of Cardiology/American Heart Association (ACC/AHA)
guidelines, European AIDS Clinical Society (EACS) Guidelines
and European Society of Cardiology and the European
Atherosclerosis Society (ESC/EAS) guidelines for cardiovascular disease (CVD) prevention [13].
Materials and Methods: A cross-sectional analysis of consecutive patients between 40 and 79 years old who had
received antiretroviral therapy for at least 12 months was
performed.
Results: Of 254 (132 from Croatia and 122 from Serbia)
persons included in the study, 76% were male; median age
was 49 years. Up to 51.6% of persons had a high CVD risk.
The prevalence of current smoking was 42.9%, hypertension
31.5% and hypercholesterolaemia ( 6.2 mmol/L) 35.4%.
Statins would be recommended to 21.3% (95% CI, 16.3% to
27.4%) of persons by the EACS, 25.6% (95% CI, 20.2% to
31.9%) by ESC/EAS and 37.9% (95% CI, 31.6 to 44.6%) by the
ACC/AHA guidelines. A high 5-year data collection on adverse
effects of anti-HIV drugs study risk score ( 5%) had a
moderate agreement with the high (]20%) 10-year CVD
Framingham risk score (kappa 0.47) and high ( ]5%) 10year European systematic coronary risk evaluation score
41
algorithm (kappa0.47), and substantial agreement with
the elevated (]7.5%) 10-year Pooled Cohort Atherosclerotic
CVD risk equation score (kappa 0.63).
Conclusion: We found a high prevalence of CVD risks in
patients from Croatia and Serbia. The ACC/AHA guideline
would recommend statins more often than ESC/EAS and
EACS guidelines.
References
1. Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Blum CB,
Eckel RH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood
Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults:
A Report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines. Circulation 2013.
2. European AIDS Clinical Society. EACS European Guidelines for
treatment of HIV infected adults in Europe Version 7. Accessible at
http://www.eacsociety.org/Guidelines.aspx. Accessed 2014/04/21.
3. European Association for Cardiovascular P. ESC/EAS Guidelines
for the management of dyslipidaemias: Eur Heart J 2011;32:
1769818.
ADVERSE EVENTS METABOLIC
P018
Randomized, crossover, double-blind, placebo-controlled
trial to assess the lipid lowering effect of co-formulated
TDF/FTC
José Ramón Santos1; Marı́a Saumoy2; Adrian Curran3; Isabel Bravo1;
Jordi Navarro3; Carla Estany1; Daniel Podzamczer2; Esteban Ribera3;
Eugenia Negredo4; Bonaventura Clotet5 and Roger Paredes5
1
Internal Medicine Department, Lluita contra la SIDA Foundation,
Hospital Universitari Germans Trias i Pujol, Barcelona, Spain. 2HIV
Unit, Infectious Disease Service, Bellvitge University Hospital,
Bellvitge Biomedical Research Institute, Hospitalet de Llobregat,
Spain. 3Infectious Diseases Department, Hospital Universitari Vall
d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
4
Lluita contra la SIDA Foundation, Hospital Universitari Germas Trias i
Pujol, Internal Medicine Department, Universitat de Vic, Barcelona,
Spain. 5Internal Medicine Department, Hospital Universitari
Germans Trias i Pujol, IrsiCaixa Foundation, Universitat de Vic,
Barcelona, Spain.
Introduction: Previous studies have described improvements
on lipid parameters when switching from other antiretroviral
drugs to tenofovir (TDF) and impairments in lipid profile
when discontinuing TDF. [13] It is unknown, however, if TDF
has an intrinsic lipid-lowering effect or such findings are due
to the addition or removal of other offending agents or other
reasons.
Materials and Methods: This was a randomized, crossover,
double-blind, placebo-controlled clinical trial (NCT 01458977).
Subjects with HIV-1 RNA B50 copies/mL during at least 6
months on stable DRV/r (800/100 mg QD) or LPV/r (400/100
mg BID) monotherapy, with confirmed fasting total cholesterol
]200 or LDL-cholesterol ]130 mg/dL and not taking lipidlowering drugs were randomized to (A) adding TDF/FTCduring
12 weeks followed by 24 weeks without TDF/FTC, or (B)
continuing without TDF/FTC for 12 weeks, adding TDF/FTC for
12 weeks and then withdrawing TDF/FTC for 12 additional
Poster Abstracts
weeks. Randomization was stratified by DRV/r or LPV/r use at
study entry. All subjects received a specific dietary counselling. Primary endpoints were changes in median fasting total,
LDL and HDL-cholesterol 12 weeks after TDF/FTC addition.
Analyses were performed by ITT.
Results: 46 subjects with a median age of 43 (4048) years
were enrolled in the study: 70% were male, 56% received DRV/
r and 44% LPV/r. One subject withdrew the study voluntarily at
week 4 and another one interrupted due to diarrhoea at week
24. Treatment with TDF/FTC decreased total, LDL and HDLcholesterol from 235.9 to 204.9 (p B0.001), 154.7 to 127.6
(p B0.001) and 50.3 to 44.5 mg/dL (p B0.001), respectively.
In comparison, total, LDL and HDL-cholesterol levels remained
stable during placebo exposure. Week 12 total cholesterol
(p B0.001), LDL-cholesterol (p B0.001) and HDL-cholesterol
(p 0.011) levels were significantly lower in TDF/FTC versus
placebo. Treatment with TDF/FTC reduced the fraction of
subjects with abnormal fasting total-cholesterol ( ]200 mg/
dL) from 86.7% to 56.8% (p 0.001) and LDL-cholesterol
( ]130 mg/dL) from 87.8% to 43.9% (p B0.001), which was
not observed with placebo. There were no virological failures,
and CD4 and triglyceride levels remained stable regardless of
exposure.
Conclusion: Coformulated TDF/FTC has an intrinsic lipidlowering effect, likely attributable to TDF.
References
1. Ananrowanich J, Nuesch R, Cote HC, et al. Changes in metabolic
toxicity after switching from stavudine/didanosine to tenofovir/
lamivudine: a Staccato trial substudy. J Antimicrob Chemoter.
2008;61:13403.
2. Llibre JM, Domingo P, Palacios R, et al. Sustained improvement of
dyslipidemia in HAART-treated patients replacing stavudine with
tenofovir. AIDS. 2006;20:140714.
3. Palacios R, Rivero A, Santos I, et al. Rapid improvement in fasting
lipids and hepatic toxicity after switching from didanosine/lamivudine to tenofovir/emtricitabine in patients with toxicity attributable
to didanosine. HIV Clin Trials. 2010 MarApr;11(2):11820.
P019
Early changes in coagulation but not inflammatory
biomarkers under intermittent ART: the randomized ANRS
106 WINDOW trial
Sébastien Gallien1; Isabelle Charreau2; Julien Fonsart3;
Samia Mourah4; Issa Kalidi5; Pierre Delobel6; Bruno Marchou6;
Jean-Pierre Aboulker2 and Jean-Michel Molina1
1
Infectious Diseases and Tropical Medicine, Hôpital Saint-Louis, APHP,
Université Paris Diderot, Paris, France. 2INSERM, SC10, Villejuif,
France. 3Laboratory of Biochemistry, Hôpital Saint-Louis, APHP,
Université Paris Diderot, Paris, France. 4Pharmacology, Hôpital
Saint-Louis, APHP, Université Paris Diderot, Paris, France.
5
Hematology Laboratory, Hôpital Saint-Louis, APHP, Université Paris
Diderot, Paris, France. 6Infectious Diseases, CHU Purpan, Toulouse,
France.
Introduction: In the SMART trial, baseline plasma hsCRP, IL6
and D-dimer levels were strongly correlated to all-cause
mortality. A case-control study has shown an increase of IL-6
and D-dimer levels after one month of antiretroviral therapy
(ART) interruption, which was correlated to viral load.
Restarting ART was associated to a decrease in D-dimer but
42
Poster Abstracts
Abstract P019Table 1. Changes in biomarkers levels in participants from the intermittent (IT) vs continuous (CT) treatment arms
through 96 weeks (*p 0.002, Wilcoxon test)
IL-6(pg/mL)
IT
Crude baseline levels:
1.58 (0.35)
sCD14(ng/mL)
hsCRP(mg/mL)
D-dimer(mg/mL)
CT
IT
CT
IT
CT
IT
2.23 (3.42)
3196 (1172)
3310 (1467)
2.60 (3.51)
6.10 (15.86)
0.30 (0.20)
CT
0.36 (0.34)
Means (SD)
Percent changes (log10
transformed) Mean
(95% CI)
From BL to week 8 (off 6
treatment)
(16; 5)
From BL to week 16 (on 3
treatment)
(14; 8)
From BL to week 96 (on 1
treatment)
(9; 8)
ND
5
1
( 5; 16)
5
( 2; 5)
( 3; 14)
8
(0; 18)
ND
ND
23*
ND
2
14
(9; 39)
4
( 4; 8)
( 30; 19)
(8; 42)
(11; 21)
(3; 16)
0
6
11
19
3
10
( 8; 10)
( 1; 14)
( 30; 13)
(6; 52)
(14; 10)
(4; 27)
not IL-6 or hsCRP levels. We assessed biomarkers levels up to
96 weeks in ART-experienced adults with plasma HIV RNA
levels B400 c/mL randomized in the ANRS 106 WINDOW trial
to intermittent ART (IT: six cycles of eight weeks of ART
interruption followed by eight weeks of ART) versus continuous treatment (CT).
Methods: Stored plasma for 160 participants (80 IT and 80
CT), matched by age, sex and CDC classification, were
analyzed blinded for IL-6, sCD-14, hsCRP and D-dimer levels
at baseline, week 8 (IT group only), week 16 and week 96.
Lower levels of detection for IL-6, sCD14, hsCRP and D-Dimer
were 1.5 pg/mL, 250 ng/mL, 0.03 mg/mL and 0.21 mg/mL,
respectively. The primary objective was to compare changes
in IL-6, hsCRP, sCD14 and D-dimer plasma levels from
baseline to week 8, 16 and 96 in the IT and CT arms.
Biomarkers levels were log10 transformed prior to analysis.
Results: At baseline, patients were mostly men (86%), with a
median age of 40 years, a CD4 T-cell count of 768/mm3,
have received a median of 4.7 years of ART and 85% had HIV
RNA B50 c/mL. Proportion of patients with plasma HIV RNA
levels B400 c/mL were 6% and 99%, 81% and 97%, 86% and
92% at weeks 8, 16 and 96 in the IT and CT arms, respectively.
Plasma biomarkers levels are shown in the Table 1.
Compared to baseline, D-dimer levels significantly increased 8
weeks after ART interruption in the IT arm (23% fold change,
95% CI 9% to 39%) but reverted to baseline levels at week
16 and remained unchanged at week 96. There was no
significant change from baseline in the other biomarker levels
in the IT arm. Similarly, no significant change from baseline in
biomarker levels was seen in the CT arm up to 96 weeks.
Conclusions: Coagulation and inflammatory biomarkers levels
remained stable over 96 weeks in well-suppressed HIVinfected patient on ART. Following ART interruption there
was a significant increase in D-dimer but not in inflammatory
biomarkers levels. This increase was reversed upon reintroduction of ART. These data suggest that ART interruption
increases coagulation rather than inflammatory biomarkers.
9
( 32; 22)
9
6
P020
Higher rates of metabolic syndrome among women taking
zidovudine as compared to tenofovir in rural Africa:
preliminary data from the CART-1 study
Niklaus Daniel Labhardt1; Molisana Cheleboi2;
Olatunbosun Faturyiele3; Mokete M Motlatsi3; Karolin Pfeiffer4;
Thabo Ismael Lejone3; Bernard Cerutti5; Jürgen Muser6; Ravi Shankar
Gupta7; Lutgarde Lynen8 and Christoph Hatz1
1
Department of Medical and Diagnostic Services, Swiss Tropical and
Public Health Institute, Basel, Switzerland. 2Laboratory Services,
Seboche Hospital, Botha-Bothe, Lesotho. 3SolidarMed, SolidarMed
Lesotho, Thaba-Tseka, Lesotho. 4SolidarMed, SolidarMed
Switzerland, Lucerne, Switzerland. 5Medical Faculty, University of
Geneva, Geneva, Switzerland. 6Central Laboratory, University
Hospitals Basel-Land, Liestal, Switzerland. 7Ministry of Health of
Lesotho, DHMT Butha-Buthe, Lesotho. 8Department of Clinical
Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Introduction: Due to its side effects stavudine (D4T) has been
replaced by zidovudine (AZT) and tenofovir (TDF) in most lowand middle-income countries (LMICs). In 2014 about 38% of
adult first-line regimens contain AZT and 62% TDF [1]. Whereas
the unfavourable metabolic outcomes of D4T in comparison to
TDF have been described extensively, studies from LMICs
comparing metabolic profiles between patients on AZT and
TDF are scarce. Given the high number of patients in LMICs still
taking AZT, data on their metabolic profile are needed. We
present rates of metabolic syndrome (MS) in adult patients
taking either AZT- or TDF-containing first-line, non-nucleoside
reverse transcriptase (NNRTI)-based regimens.
Materials and Methods: Data derived from a cross-sectional
multi-disease screening conducted in ten facilities in two
rural districts of Lesotho, Southern Africa [2]. Patients were
eligible if aged ]25 years and on NNRTI-containing first-line
ART ]6 months. The MS definition for Africa of the International Diabetes Federation was applied [3]. Assessed
potential predictors for MS were age, time on ART, virologic
suppression, body-mass index (BMI), alcohol consumption,
wealth quintile, NNRTI (nevirapine (NVP) or Efavirenz (EFV)),
history of previous D4T exposure and ART-backbone (AZT
43
or TDF). Statistical analyses stratified for sex comprised
univariate logistic regression for each predictor variable with
subsequent construction of a multivariate model including all
predictors with an association to MS at a significance
level B0.1 in univariate analysis.
Results: Out of 1026 patients, 660 (64.3%) were female. MS
prevalence was 9.8% (95% CI 6.913.4) in men and 22.9%
(19.726.3) in women. In women, aged ]35 years, AZTbackbone, NVP-base, BMI ]25kg/m2 and taking ART for
]4.5 years were associated with MS in univariate analysis.
In the multivariate model only AZT (adjusted odds-ratio: 2.2,
95% CI 1.43.6; p0.001) and BMI ]25kg/m2 (9.8; 2.8
34.1, pB0.001) were associated with MS. For men, age,
higher wealth quintile, history of D4T exposure and BMI were
associated with MS in univariate analysis. In the multivariate
model only a BMI ]25kg/m2 was associated with MS (8.9;
3.820.9, pB0.001).
Conclusion: In rural Lesotho, Southern Africa, the use of AZT
instead of TDF among women who are on ART for ]6 months
predisposes to the development of metabolic syndrome.
Given that, still 38% of first-line regimens in LMIC contain AZT,
this finding needs to be verified in other settings in SubSaharan Africa.
References
1. World Health Organization, 2014, antiretroviral medicines in lowand middle-income countries: forecasts of global and regional
demand for 20132016, technical report: aids medicines and
diagnostics service (available at: www.who.int), ISBN 978 92 4
150700 4.
2. Comorbidities and Virologic Outcome Among Patients on Antiretroviral Therapy in Rural Lesotho (CART-1 Study). www.clinicaltrials.
gov; Identifier: NCT02126696.
3. Kassi E, Pervanidou P, Kaltsas G, Chrousos G. Metabolic syndrome:
definitions and controversies. BMC Med 2011;9:48.
Poster Abstracts
P021
Long-term fat redistribution in ARV-naı̈ve HIV patients
initiating a non-thymidine containing regimen in clinical
practice
Elena Ferrer1; Antonio Navarro1; Jordi Curto1; Pilar Medina2;
Nerea Rozas1; Gladys Barrera1; Maria Saumoy1; Juan Manuel
Tiraboschi1; Carmen Gomez2 and Daniel Podzamczer1
1
Infectious diseases, Hospital Universitari de Bellvitge, Barcelona,
Spain. 2Rheumatology Department, Hospital Universitari de Bellvitge,
Barcelona, Spain.
Introduction: Lipodystrophy is still a matter of concern in
HIV patients receiving ART. However, long-term fat change
in patients taking non-thymidine regimens is not well known.
Materials and Methods: A prospective ongoing fat change
assessment including clinical evaluation and dexa scans
(Hologic QDR 4500) is being conducted in all consecutive
patients initiating ART from January 2008. Arm, leg, trunk
and total fat as well as fat mass ratio (FMR % trunk fat/%
leg fat) were determined. Patients with data at baseline (BL),
12 and 36 m are included in this analysis. ITT and OT were
performed. Multivariate general linear models were used to
assess changes in fat measures.
Results: One hundred patients were included. 81% men, 42.9
years, 18% AIDS, CD4 218.5 (6-756), viral load 5 log (2.9-6.8),
leg fat 4644g, trunk fat 6693g, FMR 0.94. Around 40 patients
(40%) initiated a PIr (17 LPVr, 11 ATVr, 9 DRVr, 3 FPVr), 34
(34%) NVP and 21 (21%) EFV. About 83% received TDF/FTC
and 10% ABC/3TC. Groups were comparable at BL except for
a lower viral load in NVP patients (p 0.047) and lower c-LDL
in PI patients (p 0.043). After 36 m, no patient presented a
clinically evident lipodystrophy. At 12 m, an overall significant
increase was found from baseline in trunk, leg and FMR
(median 759 g, 479.4 g and 0.03, respectively, pB0.05) and
at 36 m in trunk and leg fat (median 989.9 g, 566 g,
respectively, p B0.05). According to ART, at 12 m a significant
Abstract P021Figure 1. Changes in Trunk fat, Leg fat and FMR at 12 and 36 months, according to ART.
44
increase in trunk and leg fat was observed in EFV and PIr. At
36 m, in NVP patients trunk and leg fat as well as FMR
increased, whereas in PIr patients only leg fat increased (see
figure). In ITT analysis, adjusted by age, sex, risk practice and
BL CD4, EFV was associated with a greater increase in FMR
(p0.036) at 36 m vs PIr. In OT analysis, at 12 m, NVP was
associated with a smaller percentage increase in trunk fat (vs
PIr and EFV, p0.006) and in leg fat (vs PIr, p 0.046). These
differences did not persist at 36 m.
Conclusions: In this cohort of patients taking non-thymidinebased regimens, after 36 m without a clinically evident
lipodystrophy, no significant changes in FMR were observed.
However, some differences in fat redistribution according to
ART were present: PIr was associated with an initial and
continuous increase in trunk and leg fat, NVP with a slower
and progressive increase in both fat compartments, while in
EFV patients, the initial fat increase was followed by a
decrease in peripheral fat at 36 m. Longer follow up will help
to confirm these trends.
P022
Changes in lipid levels after 48 weeks of dual versus triple
therapy observed in the GARDEL study
Pedro Cahn1; Jaime Andrade Villanueva2; Jose Arribas3; Jose Gatell4;
Javier Lama5; Michel Norton6; Patricia Patterson1;
Juan Sierra Madero7; Omar Sued1; Maria Ines Figueroa1 and
Maria Jose Rolón1
1
Clinical Research, Fundacion Huesped, Ciudad Autónoma de Buenos
Aires, Argentina. 2Unidad de HIV, Hospital Civil de Guadalajara ‘‘Fray
Antonio Alcalde’’, Guadalajara, Mexico. 3Hospital Universitario La Paz,
IdiPAZ, Madrid, Spain. 4Infectious Unit, Hospital Clı́nic/IDIBAPS,
University of Barcelona, Barcelona, Spain. 5Clinical Research,
Asociación Civil Impacta Salud y Educación (IMPACTA), Lima, Peru.
6
Virology, Global Pharmaceutical Research and Development,
AbbVie, Medical Affairs Therapeutic Area, Chicago, IL, USA.
7
Department of Infectious Diseases, Instituto Nacional de Ciencias
Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
Poster Abstracts
Abstract P022Table 1. Lipid Concentrations at Baseline and
Week 48 and Mean Percentual Change
DT (n214)
Mean percentage change
Total Cholesterol
HDL-C
(%)a
BSL*
W48*
157
206
32
36
48
33
94
117
25
Non-LDL-C
120
157
30
TGs
142
222
55
LDL-C
*Units:m g/dl, mean
a
Percentage increase between baseline and week 48. Mean
percentage change was calculated at each specific time point for
each individual patient as (concentration [week X] - concentration
[baseline]) / (concentration [baseline]) 100.
to DT (55% DT vs 92% TT) (Table 1). In TT arm LDL-C and total
cholesterol elevations were lower among patients receiving
TDF compared to those treated with ZDV or ABC.
Conclusion: Changes in lipid parameters were observed in
both arms. Albeit the increase was numerically higher for
cholesterol (total and LDL-C) in DT arm while TT arm had
higher increases in TG; no difference was observed when
week 48 values were compared with the NCEP ATP III goals
for cardiovascular risk reduction [1]. So, the DT strategy, even
missing the lipid-lowering effect observed with tenofovir,
does not seem to add significant risk to patients treated with
this novel strategy.
Reference
1. Expert Panel on Detection, Evaluation, and Treatment of High
Blood Cholesterol in Adults. Executive summary of the third report of
the National Cholesterol Education Program (NCEP) expert panel on
detection, evaluation, and treatment of high blood cholesterol in
adults (adult treatment panel III). JAMA. 2001;285:248697.
Introduction: Treatment with ritonavir-boosted protease
inhibitors and nucleoside analogues frequently leads to rises
in lipids, which might increase the cardiovascular risk. The
aim of this study was to describe changes in lipid levels
among HIV positive patients participating in the GARDEL
study.
Materials and Methods: The GARDEL study compared the
efficacy and safety of a dual therapy (DT) combination of
LPV/r 400/100 mg BID3TC 150 mg BID to a triple therapy
(TT) with LPV/r 400/100 mg BID3TC or FTC and a third
investigator-selected NRTI in fixed-dose combination among
HIV treatment naı̈ve patients. We compared changes in
lipid levels from baseline to week 48 in both arms.
Results: Patient’s characteristics were well balanced regarding mean baseline total cholesterol (157 mg/dL DT, 154 mg/
dL TT), triglycerides (142 mg/dL DT, 139 mg/Dl TT), LDL-C (94
mg/dL DT, 91 mg/dL TT) and HDL-C (36 mg/dL DT, 35 mg/dL
TT). Changes in total cholesterol, LDL-C and HDL-C were
higher in DT arm, compared to TT (32% DT vs 26% TT for
cholesterol; 25% DT vs 16% TT for LDL and 33% DT vs 28% TT
for HDL). Increase in triglycerides was higher in TT compared
P023
Association between lipid genetic and immunological status
in chronically HIV-infected patients
Patricia Echeverrı́a1; Montse Guardiola2; Marta González2;
Joan Carles Vallvé2; Jordi Puig1; Anna Bonjoch1; Bonaventura Clotet1;
Josep Ribalta2 and Eugenia Negredo1
1
Fundació Lluita contra la Sida, Hospital Universitari Germans Trias i
Pujol, Badalona, Universitat Autònoma de Barcelona, HIV, Barcelona,
Spain. 2Unitat de Recerca en Lı́pids i Arteriosclerosi, Institut d’
Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Unitat de
Recerca en Lı́pids i Arteriosclerosi., Barcelona, Spain.
Introduction: Polymorphisms in some host genes have a
significant impact on susceptibility to HIV-1 infection and rate
of disease progression [1,2]. The purpose of the current substudy was to find out the relationship between polymorphisms in genes involved in the lipid metabolism and the CD4/
CD8 T-cell counts.
Methods: Sub-study of a cross-sectional, observational study
conducted in 468 patients with HIV infection attended at the
outpatient clinic to investigate individual genetic predisposi-
45
tion to atherogenic dyslipidemia (AD). All patients were
genetically characterized and all polymorphisms were in
HardyWeinberg equilibrium. Thirteen polymorphisms were
selected from nine genes: APOA5 (rs662799 and rs3135506);
APOC3 (rs5128 and rs4520); LPL (rs328 and rs268); CETP
(rs708272); HL (rs1800588); MTP (rs1800591); APOE (rs7412
and rs429358); LRP5 (rs7116604); and VLDLR (rs1454626).
Lipid and lipoprotein parameters, CD4 and CD8 T-cell counts
and plasma HIV-RNA were determinate. The statistical analysis was performed using SPSS statistical software version 19
(SPSS Inc., Chicago, IL, USA).
Results: We studied 468 HIV-infected patients (men, 77%),
with a mean (SD) age of 45.9 (19.7) years. The mean CD4 Tcell count and nadir CD4 was 547 (459) and 193 (159) cells/
mL, respectively; 78.7% of participants were virologically
suppressed. Patients carrying rs3135506 in the APOA5 gene
presented a 9% increase in circulating TG levels (p0.002)
and 10% decrease in HDLc levels (p 0.005). Such association of APOA5 towards dyslipidemia was accompanied by
a 21% decrease of the CD4 T-cell count (p 0.024) and a
19% increase in CD8 T-cell count (p0.002) in carriers of
the rare allele in the APOA5 rs662799 polymorphism
adjusted by age and gender. Patients carrying the rare allele
in rs5128 (APOC3) had a 16% decrease in circulating CD4
T cells (p 0.029); patients carrying rs1800591 (MTP)
had a 29% decrease in CD4 T cells and 14% decrease in
CD8 T cells (p 0.018 and p 0.008, respectively); patients
carrying the rare allele rs1800588 in HL had a 11% increase in
CD4 T cells (p0.043); and carriers of the rs145626 in the
VLDLR gene had 10% decrease in CD4 circulating T cells
(p0.013).
Conclusion: Variants in genes involved in the development of
AD may also influence the immunological hostvirus equilibrium in chronically HIV-infected subjects [2,3].
Poster Abstracts
References
1. Abidi SH, Shahid A, Lakhani LS, Shah R, Okinda N, Ojwang P, et al.
HIV-1 progression links with viral genetic variability and subtype,
and patient’s HLA type: analysis of a Nairobi-Kenyan cohort. Med
Microbiol Immunol. 2014;203(1):5763.
2. Christeff N, Lortholary O, Casassus P, et al. Serum lipid concentration with reference to the clinical and immunological status of
HIV infected men. Ann Med Interne. 1995;146:4905.
3. Arnedo M, Taffé P, Sahli R, et al. Contribution of 20 single
nucleotide polymorphisms of 13 genes to dyslipidemia associated
with antiretroviral therapy. Pharmacogenet Genomics. 2007;17:
75564.
P024
Lipid-lowering agents for dyslipidemia in patients who were
infected with HIV in Taoyuan, Taiwan
Shu-Hsing Cheng1; Chien-Yu Cheng1 and Na-Lee Sun2
1
Department of Infectious Diseases, Taoyuan General Hospital,
Taoyuan, Taiwan. 2Comprehensive AIDS Care Center, Taoyuan General
Hospital, Taoyuan, Taiwan.
Introduction: There is no doubt that highly active antiretroviral therapy (ART) has decreased the total mortality of
HIV-infected populations drastically, and HIV has become a
chronic and manageable condition. However, complications
after long-term treatment of ART tarnished the great efforts.
We aimed to study the effects of add-on lipid-lowering
agents on ART for patients who developed hyperlipidemia
after HIV treatment. The risk factors for failure to normalize
lipid profile were analyzed.
Materials and Methods: HIV-infected patients who visited
outpatient clinics of Taoyuan General Hospital between July
2013 and January 2014 were retrospectively reviewed. Subjects who needed the management of dyslipidemia were
Abstract P024Table 1. Characteristics and lipid profile in 76 HIV-infected patients who developed dyslipidemia after ART
treatment in Taoyuan, Taiwan
Characteristics
Patients number or mean Percentage (SD)
Total number
76
100%
Female
11
14.5%
Age
36.1
(8.9)
Body mass index
22.94
(3.79)
HIV transmission category
Injection drug users
11
14.5%
Heterosexual
13
26.3%
Men who have sex with men
52
68.4%
220.9 (median 136)
(249.5)
Nadir HIV viral load (log10)
4.95
(0.92)
Years between HIV diagnosis and regimen modification
3.09
(2.89)
Fibrate added on
16
21.5%
Statin added on
Switch to lipid-friendly ART after lipid-lowering agents
64
13
84.2%
17.1%
Baseline total cholesterol/triglyceride/high-density lipoprotein/low-density lipoprotein (mg/dL)
279/422/45/139
(85/618/15/57)
412 weeks total cholesterol/triglyceride/high-density lipoprotein/low-density lipoprotein (mg/dL)
209/270/47/114
(42/292/15/41)
48 weeks total cholesterol/triglyceride/high-density lipoprotein/low-density lipoprotein (mg/dL)
206/250/44/121
(41/205/13/36)
Nadir CD4 T cell counts
46
Poster Abstracts
Product-Limit Survival Estimates
1.0
+ Censored
Status of dyslipidemia
0.8
0.6
0.4
2:efavirenz
1:lopinavir
0.2
0:other
0.0
0
10
5
15
΄follow-up (years)΄
Log Rank p=0.003
ARTbefore
0
1
2
Abstract P024Figure 1. Kaplan-Meier analysis for 76 HIV-infected patients who received ART modification or add-on lipidlowering agents.
enrolled. Total cholesterol (TC), triglyceride (TG), high-density
lipoprotein (HDL) and low-density lipoprotein (LDL) were regularly followed up for at least 6 months. ART modification and
add-on lipid-lowering agents for dyslipidemia were analyzed.
Results: There were 926 HIV-infected patients undertaking
ART in the hospital during the study period. Among them,
23.2% of patients undergoing lopinavir-based regimen, 8.4%
efavirenz-based regimen, 4.2% darunavir-based regimen, 3.3%
nevirapine-based regimen, 2.4% raltegravir-based regimen
and 2.3% atazanavir-based regimen developed dyslipidemia.
There were 76 patients (8.2%) who needed management of
dyslipidemia (Table 1). Among them, 97% received lipidlowering agents, and 17% switched to lipid-friendly ART
(atazanavir, boosted atazanavir, boosted darunavir, nevirapine
or raltegravir) despite statins or fibrates used. Mean values
(mg/dL) of TC/ TG/LDL were, respectively, 279/422/139 before
enrolment, 209/270/114 at 412 weeks and 206/250/121 at
48 weeks (pB0.05 for baseline compared to 412 weeks and
1 year, respectively). No obvious changes in HDL were noted.
In Cox proportional hazard model, patients who received
lopinavir (adjusted hazard ratio [aHR], 0.293; 95% confidence
interval [CI], 0.1100.784; p0.015) or efavirenz (aHR, 0.185;
95% CI, 0.0720.447; p 0.005) were less likely to achieve
normalization of TC ( B200 mg/dL) and TG (B200 mg/dL).
Modification of ART (aHR, 1.807; 95% CI, 0.8283.944;
p 0.137) did not change the outcome (Figure 1).
Conclusions: Efavirenz and lopinavir were independent
factors for the persistence of dyslipidemia despite adding
lipid-lowering agents. ART associated with a favourable lipid
profile would be considered in the modern era, and this
certainly leaves the question of cost versus benefit.
Patricia Echeverrı́a1; Montse Guardiola2; Marta González2;
Joan Carles Vallvé2; Jordi Puig3; Anna Bonjoch1; Bonaventura Clotet1;
Josep Ribalta2 and Eugenia Negredo1
1
Fundació Lluita contra la Sida, Hospital Universitari Germans Trias i
Pujol, Badalona Universitat Autònoma de Barcelona, HIV, Barcelona,
Spain. 2Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira
i Virgili, Unitat de Recerca en Lı́pids i Arteriosclerosi, Barcelona,
Spain. 3Fundació Lluita contra la Sida, Hospital Universitari Germans
Trias i Pujol, Badalona, HIV, Barcelona, Spain.
Introduction: HIV-infected patients treated with Highly Active
Antiretroviral Therapy (HAART) may be predisposed to
hypertriglyceridemia, which gives rise to a highly atherogenic
lipid profile known as atherogenic dyslipidemia (AD). We
propose that genetic variability leaves some HIV-infected
patients more predisposed to AD than others [1,2].
Methods: This was a cross-sectional, observational study
conducted in 468 antiretroviral-treated HIV-infected patients
attending at the outpatient clinic of a tertiary hospital over
a 6-month period, who were classified as normolipidemic
(n 173) or presenting with AD (triglycerides: 1.7 mmol/L
and HDLc B 1.02 [men] or 1.28 mmol/L [women]) (n 148).
Polymorphisms were identified in the APOA5, APOC3, LPL,
CETP, HL, MTP, APOE, LRP5 and VLDLR genes.
Results: Atherogenic dyslipidemia was detected in 31% of
patients, most of whom were men (77%). This group was also
older and had higher levels of remnant lipoprotein cholesterol (RLPc) than normolipidemic patients. The polymorphisms rs328 in LPL, rs708272 in CETP and rs1800588 in HL
were 1040% significantly more frequent in normolipidemic
patients. At least 1 of these polymorphisms was detected in
90% of normolipidemic patients; in AD patients, the percentage decreased to 75% (p 0.003). This effect was dependent on both the allele and the dose of HAART and
independent of the regimen administered. The protective
combination showed a trend towards higher HDLc (1.13
[0.40] vs 1.24 [0.23] mmol/L), lower triglycerides (2.23 [2.34]
vs 1.89 [1.24] mmol/L) and lower RLPc (16.41 [11.42] vs
12.99 [11.69] mmol/L).
Conclusion: Polymorphisms in LPL, CETP and HL protect HIVinfected patients from developing AD in a dose-dependent
manner [3].
References
1. Veloso S, Peraire J, Viladés C, López-Dupla M, Escoté X, Olona M,
et al. Pharmacogenetics of the metabolic disturbances and atherosclerosis associated with antiretroviral therapy in HIV-infected
patients. Curr Pharm Des. 2010;16(30):337989.
2. Razzaghi H, Aston CE, Hamman RF, Kamboh MI. Genetic screening
of the lipoprotein lipase gene for mutations associated with high
triglyceride/low HDL-cholesterol levels. Hum Genet. 2000;107(3):
25767.
3. Guardiola M, Ferré R, Salazar J, Alonso-Villaverde C, Coll B, et al.
Protease inhibitor associated dyslipidemia in HIV-infected patients is
strongly influenced by the APOA5- 1131T-C gene variation. Clin
Chem. 2006;52(10):19149.
P025
P026
Polymorphisms in LPL, CETP, and HL protect HIV-infected
patients from atherogenic dyslipidemia in an allele-dosedependent manner
Estimation of the true incidence of lactic acidosis within the
Lighthouse Clinic cohort, and the likely magnitude of missed
diagnoses in the region
47
Colin Speight1; Layout Gabriel1; Sam Phiri2; Hannock Tweya3 and
Rebecca Sutherland4
1
Clinic, Lighthouse Trust, Lilongwe, Malawi. 2Directorate, Lighthouse
Trust, Lilongwe, Malawi. 3Monitoring and Evaluation, Lighthouse
Trust, Lilongwe, Malawi. 4Edinburgh RIDU, Regional Infectious
Diseases Unit, Edinburgh, UK.
Introduction: Lactic acidosis is one of the most serious side
effects associated with ART, most commonly associated with
stavudine. Clinical features are non-specific and specialist
laboratory capabilities are essential to confirm the diagnosis,
making under-diagnosis likely in resource-constrained settings. Lighthouse Trust is a tertiary referral ART centre with
over 23,500 patients on ART. The adjacent University of North
Carolina Project laboratory, also serving Kamuzu Central
Hospital, has been the only site processing lactate tests in
Central Zone for many years. Our objective was to quantify
the true incidence within our cohort, and estimate the likely
degree of historical missed diagnoses from less central ART
clinics.
Methods: All high lactate results between June 2010 and
June 2013 were treated as cases, and cross referenced with
the Lighthouse database. Patients transferring in to Lighthouse within one month prior to diagnosis were assumed to
have been referred due to their lactic acidosis, and moved to
the Central Zone cohort to avoid referral bias. Routinely
collected quarterly ART cohort data for both Lighthouse and
the entire Central Zone were analyzed.
Results: Over the three-year period, from within the Lighthouse cohort, there were 138 cases: 74% were female,
median duration on ART was 14 months (IQR 1026), and
98.5% were attributable to stavudine (only two cases to
zidovudine). Over this period, the average number of patients
taking stavudine at Lighthouse was 10,960 (3,600 on zidovudine). For the whole Central Zone (minus Lighthouse patients)
there were 61,000 on stavudine (4,830 on zidovudine), yet
only 124 cases of lactic acidosis were apparently diagnosed
from within this cohort.
Conclusion: Although cases may, of course, also have been
missed at Lighthouse, as a tertiary referral centre the rate
observed is likely to be closer to the true incidence. Over the
three years, with 138 cases from the 10,960 patients taking
stavudine at Lighthouse, it is likely that somewhere in the
region of 700 additional cases occurred amongst the 61,000
patients elsewhere in the Central Zone. This equates to
somewhere in the region of 550 missed diagnoses or 80% of
all cases. Given that the clinical sequelae of undiagnosed
lactic acidosis are either death or at best ART default, this
provides further vindication for the decision to phase out
stavudine in Malawi.
P027
Lipohypertrophy and metabolic disorders in HIV patients on
antiretroviral therapy: a systematic multidisciplinary clinical
approach
Delphine Sculier1; Laurence Toutous-Trellu2; Charlotte Verolet3;
Nicolas Matthes1; Thanh Lecompte1 and Alexandra Calmy1
1
Infectious Diseases, University Hospitals of Geneva, Geneva,
Switzerland. 2Dermatology and Venerology, University Hospitals of
Poster Abstracts
Geneva, Geneva, Switzerland. 3Pediatrics, University Hospitals of
Geneva, Geneva, Switzerland.
Introduction: Morphological and metabolic complications in
HIV patients on antiretroviral therapy remain a challenge.
While new cases of lipoatrophy (LA) disappear, irreducible
central lipohypertrophy (LH) and metabolic complications
require highly specialized management. We described a day
hospital dedicated to lipodystrophy (LD) and metabolic disorders in HIV patients on treatment in Geneva, Switzerland,
with a focus on LH.
Materials and Methods: The ‘‘Groupe Lipo & Metabolism’’ is
a multidisciplinary consultation where patients undergo a
standard evaluation including questionnaire, physical examination, dual-energy x-ray absorptiometry (DEXA) and L5-level
CT scans, blood tests and consultations with various specialists. Based on prospectively maintained data, we describe
clinical, biological and radiological characteristics of patients
]18 years who attended the consultation between 2008 and
2013. We defined LH by CT scan, the gold standard method, as
abdominal visceral adipose tissue (VAT) ]130 cm2, value
associated with increased risk of cardiovascular event.
Results: A total of 195 patients attended the consultation
during study period. Reasons for referral included LH in
28.3%, LA in 25% and mixed syndrome in 15.5% of cases.
Metabolic disorders accounted for 19% of referrals with or
without LD features. Among patients with a CT scan performed (n 183), 46 (25%) had LH with a VAT ]130 cm2. In
this population, mean age was 49.1 years and 53.6% were
male. HIV viral load was B50 cp/ml in 87% of patients. Mean
body mass index was 24.6 kg/m2. Mean waist to hip ratio
(WHR) was 0.98 for males and 0.89 for females. A total of
9.8%, 29.5% and 35% of patients had abnormal levels of total
cholesterol ( ]6.5 mmol/L), triglycerides (]2.0 mmol/L) and
HDL cholesterol (51.0 mmol/L), respectively. Mean fasting
glycaemia was 5.7 mmol/L and HbA1c was 6% in 10.5%
of patients. Vitamin-D level was B75 nmol/L in 70.7% of
patients. Respectively 31.2% and 12.1% of patients had
osteopenia and osteoporosis on the spine and 44.8% and
6.6% on the hip neck. Factors associated with a VAT ]130
cm2 included male gender (OR 3.7 [95% CI 1.78.2] pB
0.001), triglycerides ]2 mmol/L (OR 2.6 [95% CI 1.35.4]
P B0.01) and increase in BMI category (OR 1.8 [95% CI 1.2
2.8] pB0.01).
Conclusions: Lipohypertrophy is a prevalent feature of fat
redistribution among HIV patients on treatment. Risk factors
for LH include male gender, dyslipidemia and overweight.
Glucose impairment and bone disorders are also common.
A multidisciplinary approach is important to identify and
promptly address these disorders.
Acknowledgments: The ‘‘Groupe Lipo & Metabolism’’ team.
ADVERSE EVENTS RENAL
P028
Nephrolithiasis and renal failure among patients exposed to
atazanavir, other PIs and PI-free regimens
48
Ella Nkhoma1; Monica Kumar2; Patricia Hines3; Vidya Moorthy4;
Isabelle Klauck5 and Angelina Villasis Keever6
1
Bristol-Myers Squibb, Global Pharmacovigilance and Epidemiology,
Wallingford, CT, USA. 2Bristol-Myers Squibb, Global
Pharmacovigilance and Epidemiology, Hopewell, NJ, USA
3
Bristol-Myers Squibb, Center for Observational Research and Data
Science, Hopewell, NJ, USA. 4Mu Sigma, N/A, Northbrook, IL, USA.
5
Bristol-Myers Squibb, European Medical, Rueil-Malmaison, France.
6
Bristol-Myers Squibb, US Medical, Plainsboro, NJ, USA.
Introduction: Recent single-site studies and case reports
have linked atazanavir (ATV) with the occurrence of nephrolithiasis. The purpose of this study was to estimate and
compare the incidence rate of nephrolithiasis and to characterize the occurrence of subsequent renal failure among
patients on ATV, other protease inhibitors (PIs) and PI-free
regimens using real world data.
Materials and Methods: This was a retrospective cohort
analysis using claims data from a US commercial and a US
public health insurance database (Medicaid) spanning 2003
2011 and 20062011, respectively. We identified adult
HIV patients who were prescribed ATV, other PIs or PI-free
regimens with at least 6 months of continuous enrolment
prior to the index claim. Nephrolithiasis was defined as an
inpatient or outpatient ICD-9 diagnosis code for nephrolithiasis or an associated condition, plus an imaging/corrective procedure code. Renal failure was also identified using
diagnosis codes among patients experiencing nephrolithiasis.
Hazard ratios were estimated using propensity score (PS)
adjusted Cox regression, crude and adjusted for demographics, baseline comorbidities and comedications.
Results: A total of 14,477 patients (ATV: 4,150; other PIs:
4,153; PI-free: 6,174) were identified in the commercial
database: 83% male and 20% age ]50 years. In the Medicaid
database, 9,104 patients (ATV: 3,460; other PIs: 3,117; PI-free:
2,527) were identified: 53% male and 25% age ]50 years.
There were significant baseline differences in demographics,
comorbidities and concomitant medications among the three
cohorts. In adjusted analyses, ATV use was not significantly
associated with nephrolithiasis when compared to other PIs.
When ATV was compared to PI-free regimens, a positive
Poster Abstracts
association was observed in the commercial insurance but not
the Medicaid database. In both databases, previous history of
nephrolithiasis was the strongest predictor of nephrolithiasis
in the ATV/PI-free regimens contrast, but not the ATV/other
PIs contrast. For the renal failure outcomes, there were
insufficient cases across all cohorts to conduct crude or
adjusted analyses (see Table 1).
Conclusions: In this analysis of two large real world databases,
we did not find evidence of an increased risk of nephrolithiasis
among patients on ATV compared to other PIs. However,
when ATV was compared to PI-free regimens, the results
differed across the two databases, requiring further study.
Additionally, renal failure following nephrolithiasis was infrequent and not significantly different across the three cohorts.
P029
The prevalence and predictive value of dipstick urine
protein in HIV-positive persons in Europe
Amanda Mocroft1; Lene Ryom2; Giuseppe Lapadula3; Peter Reiss4;
Anders Blaxhult5; Hansjakob Furrer6; Galyna Kutsyna7; Jose Gatell8;
Josep Begovac9; Ole Kirk2 and Jens Lundgren2 for EuroSIDA in
EuroCoord
1
Department of Infection and Population Health, University
College London, London, UK. 2Copenhagen HIV Programme,
Department of Infectious Diseases, University of Copenhagen/
Rigshospitalet, Copenhagen, Denmark. 3Clinica di Malattie Infettive,
‘‘San Gerardo’’ Hospital, Monza, Italy. 4Division of Infectious
Diseases/Department of Global Health, University of Amsterdam,
Academic Medical Centre, Amsterdam, Netherlands. 5Department of
Infectious Diseases, Venhaelsan-Sodersjukhuset, Stockholm, Sweden.
6
Department of Infectious Diseases, Bern University Hospital,
University of Bern, Bern, Switzerland. 7Regional AIDS Centre, Luhansk
State Medical University, Luhansk, Ukraine. 8Infectious Diseases and
AIDS, Hospital Clinic i Provincial, Barcelona, Spain. 9Department of
Infectious Diseases, University Hospital of Infectious Diseases,
Zagreb, Croatia.
Introduction: Proteinuria (PTU) is an important marker for
the development and progression of renal disease, cardio-
Abstract P028Table 1. Incidence rates and hazard ratios of nephrolithiasis and cases of renal failure in patients on atazanavir,
other PIs and PI-free regimens
ATV vs other PIs
ATV vs PI-free
Nephrolithiasis cases/
person-years (py)
Nephrolithiasis incidence rate
per 1,000 py (95% CI)
adjusted HR
(95% CI)
adjusted HR
(95% CI)
ATV
61/4,865
12.5 (9.4, 15.7)
1.26 (0.85, 1.87)
1.65 (1.15, 2.37)
Other PIs
44/4,315
10.2 (7.2, 13.2)
Reference
PI-free
67/8,662
7.7 (5.9, 9.6)
Medicaid
ATV
Cohort
Acute renal
failure cases
Chronic renal
failure cases
Commercial
Reference
37/3,460
17.4 (12.2, 23.9)
0.93 (0.58, 1.50)
Other PIs
34/3,117
20.4 (14.1, 28.5)
Reference
PI-free
27/2,527
15.1 (10.0, 22.0)
1.31 (0.74, 2.39)
Reference
1
3
3
0
2
1
5
3
3
0
2
1
Abbreviations: ATV, atazanavir, CI, confidence interval, HR, hazard ratio, PI, protease inhibitor, py, person-years.
All comparative analyses were conducted using propensity score stratification adjustment for baseline patient characteristics.
49
Abstract P029Figure 1.
proteinuria]1+.
Poster Abstracts
Adjusted odds ratio of baseline PTA in persons with normal ( 60) eGFR PTA: 2 consecutive dipstick urine
vascular disease and death, but there is limited information
about the prevalence and factors associated with confirmed
PTU in predominantly white European HIV persons,
especially in those with an estimated glomerular filtration
rate (eGFR) of 60 mL/min/1.73 m2.
Patients and methods: Baseline was defined as the first of
two consecutive dipstick urine protein (DPU) measurements
during prospective follow-up 1/6/2011 (when systematic
data collection began). PTU was defined as two consecutive
DUP 1 ( 30 mg/dL) 3 months apart; persons with
eGFR B60 at either DPU measurement were excluded.
Logistic regression investigated factors associated with PTU.
Results: A total of 1,640 persons were included, participants
were mainly white (n 1,517, 92.5%), male (n 1296,
79.0%) and men having sex with men (n 809; 49.3%).
Median age at baseline was 45 (IQR 3752 years), and CD4
was 570 (IQR 406760/mm3). The median baseline date was
2/12 (IQR 11/116/12), and median eGFR was 99 (IQR 88
109 mL/min/1.73 m2). Sixty-nine persons had PTU (4.2%, 95%
CI 3.24.7%). Persons with diabetes had increased odds of
PTU, as were those with a prior non-AIDS [1] or AIDS event
and those with prior exposure to indinavir. Among females,
those with a normal eGFR (90) and those with prior
abacavir use had lower odds of PTU (Figure 1).
There was no significant association between past or current
use of tenofovir, lopinavir, atazanvir (boosted or unboosted)
or any other boosted PI and PTU (p 0.2). During 688.2
person-years of follow up (PYFU), three persons developed
chronic kidney disease (CKD; confirmed [3 months apart]
eGFR B60); 2/685 (0.3%) without PTU and 1/38 (2.8%) with
PTU (p 0.032). The crude incidence of CKD in those with
baseline PTU and eGFR60 was almost 10 times higher than
in those without baseline PTU and eGFR60 (rate ratio 9.61;
95% CI 0.87105.9, p0.065).
Conclusions: One in 25 persons with eGFR 60 had confirmed
proteinuria at baseline. Factors associated with PTU were
similar to those associated with CKD. The lack of association with antiretrovirals, particularly tenofovir, may be
due to the cross-sectional design of this study, and additional
follow-up is required to address progression to PTU in those
without PTU at baseline. It may also suggest other markers are
needed to capture the deteriorating renal function associated with antiretrovirals may be needed at higher eGFRs.
Our findings suggest PTU is an early marker for impaired renal
function.
Reference
1. Mocroft A, Reiss P, Gasiorowski J, Ledergerber B, Kowalska J,
Chiesi A, et al. Serious fatal and non-fatal non-AIDS defining illnesses
in Europe. JAIDS. 2010;55:26270.
P030
Impact of NRTI backbone on renal, bone and cardiovascular
markers in HIV-infected individuals receiving a boosted
protease inhibitor
Tristan Barber; Andrew Hill; Gurmit Jagjit Singh; Marta Boffito;
Mark Nelson and Graeme Moyle
Chelsea and Westminster NHS Foundation Trust, St Stephen’s AIDS
Trust Clinical Trials Unit, London, UK.
50
Poster Abstracts
Introduction: We have previously shown in the SSAT 044
study that unconjugated hyperbilirubinaemia in subjects
receiving a boosted protease inhibitor (PI/r) has limited
impact on renal, cardiovascular (CV) and bone biomarkers, as
well as on neurocognitive performance, relative to those
receiving PI/r with a normal bilirubin. We present here a
secondary analysis comparing markers in those receiving
abacavir- vs tenofovir- based antiretroviral therapy (ART).
Materials and Methods: This cross-sectional study included
101 HIV-1 infected individuals stable (HIV RNAB50 cps/ml,
6 months) on antiretroviral regimens including tenofovir
(TDF)/emtricitabine or abacavir/lamivudine plus a ritonavir
boosted PI.
Results: Forty-three subjects had normal bilirubin (NBR)
levels and 35 had high bilirubin (2.5 times upper limit);
the remaining 23 patients had intermediate bilirubin levels or
violated the protocol. The mean age of participants was 48
years; 93% were male and 84% Caucasian; 22 received ABCbased therapy and 78 TDF. No differences were seen in
cardiovascular markers: Framingham (10-year risk % median,
IQR): ABC 8.1, 5.615.3; TDF 9.5, 4.813.4 (p ns); pulse
wave velocity and carotid intimal thickness also showed no
significant differences. No differences were seen in bone
parameters: Calcaneal Stiffness Index (median score, IQR):
ABC 0.5, 0.8 to 0.8; TDF 0.5, 1.40.4 (p ns); 10 year
FRAX score (% median, IQR): ABC 5.0, 2.46.2; TDF 3.6, 2.5
5.8 (p ns). There were differences in renal parameters as
shown in Table 1. We show statistically significant differences
in urine protein/creatinine ratio (uPCR) (10 vs 7; p0.004)
and urine albumin/creatinine ratio (uACR) (15 vs 8; p
0.002), with both being higher in the TDF group.
Conclusions: Tenofovir use is associated with excess loss of
proteins including those typically resorbed in the renal
tubule. Abacavir use was not associated with an increase in
biomarkers of CV risk or vascular dysfunction.
P032
Prevalence and European AIDS Clinical Society (EACS)
criteria evaluation for proximal renal tubular dysfunction
diagnosis in patients under antiretroviral therapy in routine
setting
Lorenzo Pitisci; Rémy Demeester and Jean-Claude Legrand
Hopital Civil de Charleroi, Belgium Infectious Disease, AIDS Reference
Center, Charleroi, Belgium.
Introduction: Tenofovir (TDF) is an antiretroviral drug
often used in combination regimen in HIV-positive patients.
Adverse effects affecting kidneys consist in an increase or
a new onset proteinuria, a decrease of glomerular filtration
rate (GFR), and/or a proximal renal tubular dysfunction
(PRTD) that rarely leads to Fanconi’s syndrome. EACS guidelines propose to screen PRTD in patients with chronic
renal insufficiency, with a sudden decrease of eGFR, with
hypophosphataemia (if non-renal causes such as vitamin D
deficiency are excluded) and with a new onset proteinuria.
We aim to evaluate the prevalence of PRTD by comparing
the group of patients under TDF to the group free of TDF, in
our cohort of 300 patients. We also aim to evaluate the
accuracy of EACS criteria for screening PRTD in routine
settings and to assess the utility of urinary samples in PRTD
diagnosis.
Materials and Methods: During two consecutive years,
we collected annually blood and urine samples at the same
time in our outpatient clinic. We assessed kidney function,
plasma levels and fractional excretion of phosphate, uric acid,
potassium, plasma glucose and proteinuria. PRTD was defined
by the presence of at least two out of the five following criteria:
fractional excretion (FE) of phosphate 20% (or 10%
when serum phosphate B0.8 mmol/L), non-diabetic glycosuria (positive urine glucose with plasma glucose B70 mg/dL),
renal tubular acidosis (urinary pH 5.5 and serum bicarbonate
B21 mmol/L), uric acid FE 10% or potassium FE 10%.
After the first year, patients with TDF regimen who were
diagnosed with PRTD were shifted to TDF-free regimen and
included again in the study.
Results: For PRTD (first line), they are expressed in number
of diagnoses/total number of patients in this group.
The second line resumes the number of PRTD diagnose
patients who should have been screened according to EACS
criteria.
Conclusions: PRTD screening according to EACS criteria is
not sufficient to diagnose every case, especially minor PRTD,
mainly because the prevalence is low and its diagnosis remains difficult in routine settings. We recommend performing a urine test including proteinuria every year for patients
undergoing TDF treatment. The next step will be to follow
Differences in renal parameters
ABC use
Parameter
No ABC use
Median (IQR)
N
Median (IQR)
N
p Value
Protein/creatinine ratio (mg/mmol)
7 (69)
18
10 (814)
67
0.004
Urinary retinol binding protein/creatinine ratio (ug/mmol)
8 (610)
ABC use
19
15 (8240)
No ABC use
67
0.002
N
Number normal (%)
Parameter
N
p Value
Protein/creatinine ratio (mg/mmol)
Number normal (%)
16 (89)
18
49 (73)
67
0.137
Urinary retinol binding protein/creatinine ratio (ug/mmol)
19 (100)
19
50 (75)
67
0.008
51
Poster Abstracts
Abstract P032Table 1. The table summarises our results
PRTD
Screening
TDF
TDF TDF
TDF
YEAR 1
YEAR 1
YEAR 2
YEAR 2
11/113
2/43
9/91
9/58
9/11 (82%)
1/2 (50%)
7/9 (78%)
8/9 (89%)
accuracy
PRTD patients to evaluate the time laps until full recovery after
TDF shift.
References
1. Dauchy FA, Lawson-Ayayi S, de La Faille R, Bonnet F, Rigothier C,
Mehsen N, et al. Increased risk of abnormal proximal renal tubular
function with HIV infection and antiretroviral therapy. Kidney Int.
2011;80(3):3029.
2. EACS guidelines version 7.0, October 2013, page 42.
P033
The impact of tenofovir disoproxil fumarate on kidney
function: four-year data from the HIV-infected outpatient
cohort
Nadine Monteiro; Margarida Branco; Susana Peres; Fernando Borges
and Kamal Mansinho
Infectious Diseases and Tropical Medicine, Hospital Egas Moniz,
Lisbon, Portugal.
Introduction: With improvements in survival and disease
progression in the era of combined antiretroviral therapy,
complications such as kidney disease are becoming increasingly prevalent in HIV-infected patients. Tenofovir disoproxil
fumarate (TDF) has been associated with nephrotoxicity,
including decline in glomerular filtration rate, proximal
tubular damage and acute kidney injury.
Objective: Characterize kidney safety of TDF-containing antiretroviral treatment (ART) regimens in HIV-infected patients.
Methods: Non-controlled, observational, retrospective study
was based on the clinical files registry of HIV patients
who started TDF between January and December 2008.
We assessed outpatients followed at a single Portuguese
center. Demographic, clinical, virological and immunological
data at baseline were collected. Serum creatinine, estimated
glomerular filtration rate (eGFR) and creatinine clearance
(CrCL) were assessed at baseline, after six months and every
year up to four years. CrCL and eGFR were calculated by
CockroftGault and Modification of Diet in Renal Disease
equations, respectively.
Results: A total of 176 patients (71.6% males) with a mean
age of 43 years were enrolled. Ninety-six (52%) were ARTnaive patients at TDF initiation. At baseline 12.5% had
hypertension, 4% diabetes, 25% chronic hepatitis C and
9% chronic hepatitis B infections; 58% had normal renal
function (eGFR ]90 ml/min/1.73 m2), 36% had mild (eGFR
60-89 ml/min/1.73 m2) renal dysfunction and 2.3% had
moderate (eGFR 30-59 ml/min/1.73 m2) renal dysfunction
at initiation of TDF. Eighty-three (47%) patients were on
protease inhibitors and the remaining on NNRTIs containing
regimens. During 48 months follow-up, 5% experienced
moderate renal dysfunction and 1.7% severe renal dysfunction. Twenty-one (12%) patients met the definition criteria
of rapid decline of renal function (annual decline of eGFR
]3 ml/min/1.73 m2 in two consecutive years). The development of kidney events was associated with age above
50 years, presence of comorbidities and advanced stage HIV
infection (p 0.05 in univariate analysis).
Conclusions: These data reveal a favourable renal safety
profile of TDF, during a four-year follow-up. Screening for
kidney disease markers, regular follow-up and control and
prevention of risk factors for renal failure are crucial for
adequate management of HIV-infected patients.
P034
Investigating presentations and outcomes of a joint HIV
renal clinic
Jake Scott1 and Deborah Williams2
1
Lawson Unit, Brighton and Sussex Medical School, Brighton,
UK. 2Lawson Unit, Brighton and Sussex University Hospitals,
Brighton, UK.
Introduction: HIV patients are at risk of renal dysfunction
directly from HIV, indirectly from chronic inflammation as
well as from antiretroviral drug toxicity. In particular,
tenofovir (TDF) has been associated with proximal renal
tubular dysfunction. A joint HIVrenal clinic was set up in
2009 to facilitate a timely review and minimize additional
follow-up appointments. Brighton has a cohort of 2,150 HIV
patients, 90% are on ARVs with 910/1,935 (47.0%) on
regimens including TDF. This study aims to investigate the
utility of this clinic and describe renal disease in this cohort.
Materials and Methods: Notes of patients scheduled for
assessment at the clinic between 2012 and 2014 were
reviewed. Demographics, HIV history, number of visits, reason
for referral and outcome information were collected.
Results: Sixty-five patients, median age 51 years (2888) and
median duration of HIV 163 months (20335), were reviewed. Forty-two were taking TDF for a mean of 55.8 months
(9122). Forty-two patients were reviewed once with a
median number of visits of 1 (14).
Of those on TDF with proteinuria, 5 (13.2%) had TDF toxicity
diagnosed and were discontinued at once, 27 continued with
close monitoring with a further 7 subsequently discontinuing;
total discontinued were 12 (32%). Overall, blood pressure
control was the commonest intervention, 23/65 (35.4%), with
8/12 (66.7%) in the non-TDF proteinuria group. Four (6%)
patients underwent renal biopsy (2 focal segmental glomerulosclerosis, 1 IgA nephropathy and 1 glomerulonephritis and
granuloma). In 4 (6%) creatinine rise was attributed to NSAIDs,
creatine or protein supplements usage.
Conclusions: TDF toxicity was the commonest reason for
referral but only a minority (13.2%) needed to discontinue
immediately. Optimizing BP control was the most frequent
outcome suggesting this is an underappreciated cause for renal
dysfunction amongst HIV physicians, as were other causes
such as creatine and protein supplement usage. Running a
52
Poster Abstracts
Reasons for referral to HIV-renal clinic
Reason for referral
Frequency
Proteinuria on TDF
Proteinuria not on TDF
38 (58%)
12 (18%)
Raised creatinine without proteinuria
15 (23%)
‘‘one-stop-shop’’ clinic supports continuation of tenofovir in
patients with proteinuria, and supports the diagnosis and
management of poorly controlled hypertension and streamlines the management of these patients.
ADVERSE EVENTS BONE
P035
Prevalence of low bone mineral density among HIV patients
on long-term suppressive antiretroviral therapy in resource
limited setting of western India
Ameet Dravid; Milind Kulkarni; Amit Borkar and Sachin Dhande
HIV Medicine, Ruby Hall Clinic, Pune, India.
Baseline characteristic of patients with normal and low BMD
Characteristic
Age (median, IQR)
BMI (median, IQR)
Lipoatrophy, n (%)
Steroid, n (%)
Smoking, n (%)
Alcohol, n (%)
Diabetes, n (%)
Baseline CD4, median (IQR)
ART experienced, n (%)
Characteristic
Introduction: Bone mineral density (BMD) assessment in HIV
patients is sparsely done in resource limited settings.
Materials and Methods: We conducted a cross-sectional study
of BMD amongst HIV patients following up in our clinic from 1
June to 1 December 2013 by performing dual-energy X-ray
absorptiometry scan (Lunar Prodigy Advanced DXA System,
GE Healthcare) of lumbar spine and hip. Patients on long
term (]12 months), virologically suppressive antiretroviral
therapy (ART) were included. Patients who were ART naı̈ve
were included as control population. Virologic failures were
excluded. Low BMD was defined by WHO T-score criteria
(normal: T score ] 1;osteopenia: T score between 1 and
2.5 SD; osteoporosis: T score 5 2.5 SD). Baseline risk factors associated with low BMD like age, low BMI, lipoatrophy,
diabetes mellitus, current smoking, current alcohol intake,
steroid exposure and menopause were recorded. ART-related
factors associated with low BMD like ART duration, exposure to
tenofovir and exposure to protease inhibitors (PI) were studied.
Results: A total of 536 patients (66% males, 496 ART
experienced and 40 ART naı̈ve) were included in this analysis.
Median age was 42 years, mean BMI 23.35 kg/m2 and median
CD4 count 146 cells/mm3. All ART experienced patients had
plasma viral load B400 copies/ml.
Prevalence of low BMD amongst ART naive and ART experienced patients was 67% (osteopenia: 70.4%, osteoporosis:
Overall
Normal BMD
Low BMD
P value
42 (3748)
23.3 (20.226.4)
61 (11%)
47 (9%)
26 (5%)
56 (10%)
26 (5%)
146 (72131)
496 (90%)
39 (3544)
25.4 (22.228.6)
8 (7%)
7 (6%)
2 (2%)
12 (11%)
5 (5%)
179 (76287)
97 (88%)
44 (3849)
22.8 (19.725.8)
53 (12%)
40 (9%)
24 (6%)
44 (10%)
21 (5%)
140 (72220)
399 (94%)
P B0.001
P B0.001
0.13
0.32
0.1
0.86
0.87
0.046
0.05
Univariate and multivariate regression analysis of risk factors associated with low BMD
Unadjusted OR
95% CI; p value
Adjusted OR
95% CI; p value
Age
1.05
1.02,1.06; p B 0.001
1.06
1.03,1.09; p B 0.001
Female gender
1.01
0.64,1.57; p 0.97
1.32
0.82,2.16; p 0.26
BMI
0.89
0.85,0.93; p B 0.001
0.86
0.82,0.91; p B 0.001
Lipoatrophy
1.81
0.83,3.93; p 0.13
Steroid
1.52
0.66,3.5; p 0.32
1.41
0.58,3.4; p 0.45
Smoking
3.22
0.75,13.85; p 0.12
4.84
1.01,23.3; p 0.05
Alcohol
Menopause
0.94
9.89
0.48,1.88; p 0.86
2.29,42.8; p 0.002
Baseline CD4 count
0.92
0.88,0.97; p 0.003
0.96
0.9,1.03; p 0.28
ART exposure
1.98
0.99,3.98; p 0.05
1.18
0.48,2.87; p 0.28
TDF exposure
1.18
0.58,2.4; p 0.65
53
29.6%) and 80.4% (osteopenia: 63.4%, osteoporosis:36.6%),
respectively (p 0.05). Mean T scores at lumbar spine and hip
for ART naive and ART experienced patients were 1.37 and
0.9 versus 1.56 and 1.48 (p 0.05), respectively. Age,
low BMI, current smoking, menopause, baseline CD4 count
and exposure to ART were factors significantly associated with
low overall BMD on univariate regression analysis. On multivariable logistic regression analysis age (p B0.001), low BMI
(p B0.001), current smoking (0.05) and menopause (0.03)
were associated with low BMD. BMI decrease of 1 kg/m2 and
baseline CD4 decline of 50 cells/mm3 lead to 14% and 4%
increased probability of low BMD, respectively. Choice of
antiretroviral use (tenofovir vs non-tenofovir, PI vs No PI) did
not influence loss of BMD.
Conclusions: Extremely high prevalence of accelerated BMD
loss amongst ART naı̈ve and ART experienced patients in our
cohort is a matter of deep concern due to its association with
pathological fractures. Bone mineral loss was seen irrespective of ART used. Association of low BMD with low baseline
CD4 count strengthens the case for early ART.
P036
No association between vitamin D deficiency and
parathyroid hormone, bone density and bone turnover in a
large cohort of HIV-infected men on tenofovir
Amanda Samarawickrama1; Sophie Jose2; Caroline Sabin2;
Karen Walker-Bone3; Martin Fisher4 and Yvonne Gilleece4
Poster Abstracts
1
Clinical Investigation and Research Unit, Brighton and Sussex
Medical School, Brighton, UK. 2Department of Infection
and Population Health, University College London, London,
UK. 3MRC Lifecourse Epidemiology Unit, University of
Southampton, Southampton, UK. 4Department of HIV and GU
Medicine, Brighton and Sussex University Hospitals, Brighton, UK.
Introduction: Combination antiretroviral therapy (cART) may
affect vitamin D [25(OH)D], parathyroid hormone (PTH), bone
mineral density (BMD) and bone turnover (BT). Reduced BMD
and secondary hyperparathyroidism have been reported with
tenofovir (TDF). We investigated the associations between
TDF and bone markers, especially in 25(OH)D-deficient
patients.
Materials and Methods: In a single-centre longitudinal study
investigating BMD in HIV-positive men, serum 25(OH)D,
calcium, phosphate, PTH and alkaline phosphatase (ALP)
were measured. Lumbar spine, non-dominant total hip and
non-dominant femoral neck BMD (g/cm2) were measured
using dual-energy X-ray absorptiometry. BT was assessed by
serum type 1 procollagen (P1NP) and carboxy-terminal
collagen cross-links (CTX). MannWhitney U tests compared
serum markers and BT, and t-tests compared BMD according
to TDF in all and 25(OH)D-deficient patients.
Results: A total of 422 men were recruited: mean age 47 (SD
9.8) years, 94% white ethnicity, 93% MSM, diagnosed HIV
positive for median 9.6 (IQR 5.0,15.5) years, median CD4 547
(IQR 411,696) cells/mL, HIV RNA B40 copies/mL in 87% (96%
of those on cART). 25(OH)D (nmol/L) was normal ( 75),
insufficient (5075), deficient (2550) and severely deficient
Abstract P036Figure 1. Association between 25(OH)D and PTH according to current TDF use.
54
Poster Abstracts
Bone markers, BMD, 25(OH)D and TDF use
b) 25(OH)D
a) All patients
PTH, ng/L, median (IQR)
TDF cART
Non-TDF cART
(n 293)
(n 88)
B 50 nmol/L
P-value
TDF cART
Non-TDF cART
(n 166)
(n 49)
p Value
48 (36, 55)
51 (39, 65)
0.54
46 (36, 64)
47 (38, 62)
0.55
1.131 (0.146)
1.149 (0.174)
0.41
1.130 (0.153)
1.156 (0.176)
0.32
0.995 (0.133)
0.986 (0.144)
0.61
0.989 (0.140)
0.997 (0.151)
0.76
0.944 (0.124)
0.945 (0.180)
0.96
0.940 (0.129)
0.935 (0.137)
0.83
P1NP, ng/mL, median (IQR)
13.61 (5.55, 32.37)
10.95 (5.52, 24.83)
0.52
14.49 (5.83, 40.68)
12.66 (6.48, 23.95)
0.60
CTX, ng/mL, median (IQR)
1.94 (0.85, 4.84)
2.39 (1.02, 5.33)
0.29
2.02 (1.03, 4.84)
2.48 (1.17, 5.65)
0.32
Lumbar spine BMD, g/cm2,
mean (SD)
Non-dominant total hip BMD,
g/cm2, mean (SD)
Non-dominant femoral neck
BMD, g/cm2, mean (SD)
( B25) in 14%, 29%, 50% and 7%, respectively. Of 381 men
on cART, 77% were currently on TDF. TDF was not associated
with median calcium (p 0.69) or phosphate (p 0.52), but
patients had higher (but normal) median ALP [81 (IQR
69,103) vs. 73 (IQR 60,89) IU/L, p0.005) compared to
non-TDF cART. There was no difference in the association
between vitamin D and PTH according to whether someone
currently was (r 0.11, p0.06, Figure 1) or was not using
TDF (r 0.12, p0.29, Figure 1). TDF was also not associated
with PTH, BMD or BT in either all patients on cART (Table 1a)
or in patients with 25(OH)D deficiency (Table 1b).
Conclusions: In this largely TDF-experienced cohort of HIVpositive men, there was no association between TDF and
25(OH)D deficiency, hyperparathyroidism, reduced BMD or
increased BT, although patients on TDF had higher but
normal ALP. We found no evidence to support additional
monitoring of bone markers in patients on TDF regardless of
25(OH)D status.
P037
Relationship between body mass index and bone mineral
density in HIV-infected patients referred for DXA
Carmela Pinnetti1; Lupi Federico1; Patrizia Lorenzini1;
Chiappetta Domenico2; Bellagamba Rita1; Loiacono Laura1;
Mauro Zaccarelli1; Stefania Cicalini1; Raffaella Libertone1;
Alberto Giannetti1; Silvia Mosti1; Elisa Busi Rizzi2; Andrea Antinori1
and Adriana Ammassari1
1
National Institute for Infectious Disease, Clinical Department, Rome,
Italy. 2National Institute for Infectious Disease, Radiological
Department, Rome, Italy.
Introduction: Reduced bone mass density (BMD) is a
frequent observation in HIV-infected persons. Relationship between body mass index (BMI), weight, height and
BMD was reported for many populations. In particular,
BMI has been found to be inversely related to the risk of
osteoporosis.
Methods: This is a cross-sectional, monocentric study where
all HIV-infected patients referred to first DXA scan in clinical
routine during 20102013 were included. Osteopenia and
osteoporosis were defined by T- score B 1 and B 2.5,
respectively. Patients were categorized according to WHO
BMI classification: underweight B18.5 kg/m2; normal
weight 18.524.9 kg/m2; over weight 2529.9 kg/m2; obese
30 kg/m2. Statistical analysis was carried using logistic
regression.
Results: A total of 918 patients were included: median age 49
years (IQR, 4455); 59.4% male; 93% Caucasian. Median
anthrometric characteristics were: 68 kg (IQR, 5978); 1.7 m
(IQR, 1.61.75); 23.5 kg/m2 (IQR, 21.426.2). Underweight
was found in 5%, normal weight in 61%, overweight in 26% and
obesity in 8% of patients. According to T-scores, 110 (11.2%)
patients were osteoporotic and 502 (54.7%) had osteopenia. In
the femoral neck area, the prevalence of osteoporosis was
slightly lower (5.7%) than lumbar spine site (9.2%). Agreements between sites of T-scores for the diagnosis of osteoporosis were 26 and 172 and 346 for osteopenia and normal
BMD values, respectively. T-scores at femoral neck or lumbar
spine positively correlated with BMI (pB0.001) (Figure 1).
Among predictors of osteopenia/osteoporosis, univariable
analysis showed: older age (p B0.0001); lower weight (p B
0.0001); increasing height (p B0.002). Patients underweight
had a higher risk of osteopenia (p 0.02) as well as of
osteoporosis (p 0.003). Patients with BMI above normal
had a reduced risk of low BMD (osteopenia p B0.0001;
osteoporosis pB0.03). Controlling for calendar year, gender,
ethnicity, and age, BMI was confirmed as risk factor if below
normal (AdjOR of osteopenia 2.42 [95% CI 1.165.07]
p0.02; AdjOR of osteoporosis 3.22 [95% CI 1.606.49]
p0.001).
Conclusions: Our findings indicate that almost 66% of HIVinfected patients have subnormal bone mass. Further, as in
other patient populations, in the HIV infection also low BMI
is an important risk factor for osteopenia/osteoporosis. This
finding highlights the compelling need for standardized
55
Poster Abstracts
Abstract P037Figure 1. Scatterplot of BMI by frmoral and lumber t-score. Linear regression line was fitted.
screening actions, particularly in patients weighting below
normal.
P038
Prevalence of osteoporosis and predictors of low BMD in a
cohort of HIV-1-infected patients in Rome: features of a
population at high risk
Alessandro D’Avino1; Annapia Lassandro2; Silvia Lamonica1;
Benedetta Piccoli1; Massimiliano Fabbiani1; Annalisa Mondi1;
Roberta Gagliardini1; Alberto Borghetti1; Iuri Fanti1;
Federico Pallavicini1; Roberto Cauda1 and Simona Di Giambenedetto1
1
Department of Clinical Infectious Diseases, Catholic University of
Sacred Heart, Rome, Italy. 2Department of Endocrinology, Catholic
University of Sacred Heart, Rome, Italy.
Introduction: Ageing of HIV-infected patients led to an
increasing rate of osteopenia and osteoporosis. The cause is
multifactorial, including virus activity, drug toxicity and host
factors. The aim of our analysis is to quantify this issue
according to our department experience and to evaluate
predictors of low BMD.
Materials and Methods: HIV-1-infected patients, on stable
HAART, were consecutively enrolled in this cross-sectional
study and underwent DEXA. We analyzed the prevalence and
evaluated predictors of low BMD in our population.
Results: We collected data from 208 patients, 148 of whom
were male, with 49 years median age (IQR 24.168.3). About
39% of patients were heterosexuals, 33.7 MSM and 12.5%
were IDU, 40.4% were smokers. Caucasians were 93.3%, and
13.9% were co-infected with HCV virus. Around 6.7% of
patients were on their first HAART regimen and all of them
started TDF. Their median time of HAART exposure was 1.17
years (IQR 0.81.6). Conversely, median time of HAART
exposure of multi-experienced patients was 8.5 years (IQR
3.112.0). We stratified DEXA results for patients on first-line
regimen versus multi-experienced one. We found that 42.9%
of patients on first-line HAART had low BMD of lumbar spine
and 7.1% had osteoporosis. Regarding the multi-experienced
group of patients, lumbar spine osteopenia was observed in
36.6% of patients and 15.5% of them had osteoporosis.
Median age of patients with low BMD of lumbar spine was
45.6 (IQR 24.168.3) for patients on first-line regimen and
49.8 years for multi-experienced (IQR 44.254.0) regimen.
We found similar data for BMD of hip, but no patients in the
first group had hip osteoporosis. We also analyzed predictors
of low BMD in our population. MSM patients showed a 3.4fold higher risk to have osteoporosis of lumbar spine (OR
3.41, CI 1,1059,269, p0.03). As expected, we found that
non-Caucasian patients had 13.5-fold higher risk to have
osteoporosis of the hip (OR 13.52, CI 1.5122.7, p0.02).
Exposure to HAART was also evaluated, but no predictors
were found.
Conclusions: Our data confirm how osteoporosis is highly
prevalent and occurs earlier in HIV-infected patients. Antiretrovirals play a crucial role. In our experience loss of BMD
can occur within a year of treatment, when almost half of our
patients starting TDF had a low BMD. MSM patients have a
higher risk to develop spine osteoporosis and non-Caucasian
patients are more likely to have hip osteoporosis. We remark
the importance of BMD assessment for HIV-infected patients
especially during their first months of treatment.
ADVERSE EVENTS OTHER
P039
Co-administration of ritonavir-boosted protease inhibitors
and rate of tenofovir discontinuation in clinical practice
Silvia Costarelli1; Alessandro Cozzi-Lepri2; Giuseppe Lapadula1;
Stefano Bonora3; Giordano Madeddu4; Franco Maggiolo5;
Andrea Antinori6; Andrea Gori1 and Antonella D’Arminio-Monforte7
1
Infectious Diseases, San Gerardo Hospital, Monza, Italy. 2Virology,
Royal Free and University College Medical School, London,
UK. 3Infectious Diseases, University of Torino, Torino,
Italy. 4Infectious Diseases, University of Sassari, Sassari, Italy.
5
Infectious Diseases, Papa Giovanni XXIII Hospital, Bergamo, Italy.
6
Infectious Diseases, Spallanzani Hospital, Rome, Italy. 7Infectious
Diseases, University of Milan, Milano, Italy.
Introduction: In clinical trials, toxicity leading to discontinuation of tenofovir (TDF) is a rare occurrence (3% by two
years)[1,2]; however, in clinical practice it seems to be higher.
Previous studies suggested that TDF toxicity is higher when it
is co-administered with ritonavir-boosted protease inhibitors
(PI/r)[3,4]. The aim of this study is to assess the rate of TDF
56
discontinuations in clinical practice and to explore associated
factors.
Methods: All previously antiretroviral-naı̈ve patients initiating
a TDF-containing regimen were selected from the ICONA
cohort, unless they were positive for hepatitis B. The primary
outcome was TDF discontinuation (30 days) regardless of
the reason, the secondary was TDF discontinuation due to
toxicity. All analyses were repeated for the isolated stop of
TDF (no stop of associated drugs). The main reason for
discontinuation as reported by the treating physicians was
used to classify stops. KaplanMeier (KM) analysis and Cox
proportional hazards model were used.
Results: A total of 3,303 naı̈ve patients were enrolled: 674
(20.4%) were female, the median age was 38 years (3245),
55% were on PI/r-based regimen and 45% on NNRTI; 80% of
calculated estimated glomerular filtration rates (eGFR) were
90 ml/min. The probability of discontinuation of TDF
regardless of the reason was 10% (95% CI 811) at two years,
20% by eight years. The causes of discontinuation were:
toxicity (33%), failure (10%), non-adherence (21%), simplification (16%) and other/unknown causes (20%). The five-year KM
estimates in the PI/r vs. not PI/r groups were 23% vs. 10%,
respectively (log-rank p0.0001), for the outcome of stopping regardless of the reason, and 8% vs. 4% (p 0.18) for
discontinuation due to toxicity. In a multivariable Cox model,
PI/r use and lower body weight were associated with
increased risk of discontinuing TDF regardless of the reason;
lower eGFR at baseline was associated with TDF discontinuation for toxicity and PI/r use was associated with isolated stop
of TDF (Figure). No differences in rates of TDF discontinuations
between PIs were found.
Conclusion: In our cohort, the observed frequency of TDF
discontinuations was low although higher than estimated in
clinical trials (10% by two years). Co-administration of TDF
with PI/r was associated with an increased rate of TDF
discontinuations. This finding should guide further investigations of the mechanism that may have led to discontinuation
of TDF in patients using PI/r.
Poster Abstracts
References
1. Gallant JE, Winston JA, DeJesus E, et al. AIDS. 2008 Oct 18;22(16):
215563.
2. Arribas JR, Pozniak AL, Gallant JE, et al. J Acquir Immune Defic
Syndr. 2008 Jan 1;47(1):748.
3. Goicoechea M, Liu S, Best B, et al. J Infect Dis. 2008 Jan 1;197(1):
1028.
4. Focà E, Motta D, Borderi M, et al. BMC Infect Dis. 2012 Feb 14;
12:38.
P040
Acceptance rate of clinical study endpoints and adequacy of
source documentation: experience from clinical study
endpoint review in NEAT001/ANRS143
Juan Berenguer1; Ferdinand Wit2; Per O Jansson3;
Christine Schwimmer4; Justyna D Kowalska5; Juliette Saillard6;
Alpha Diallo6; Anton L Pozniak7; François Raf8 and Jesper Grarup3
1
Hospital General Universitario Gregorio Marañon, ID, Madrid, Spain.
2
Department of Global Health, Amsterdam Institute for Global Health
and Development, AMC, Amsterdam, Netherlands. 3CHIP,
Department of Infectious Disease and Rheumatology, Rigshospitalet,
University of Copenhagen, Copenhagen, Denmark. 4INSERM,
U897, Bordeaux, France. 5Wojewodzki Szpital Zakazny, ID
Warszawa, Poland. 6ANRS, Service de recherches cliniques et
thérapeutiques, Paris, France. 7Chelsea and Westminster Hospital,
NHS Foundation Trust, ID, London, UK. 8University Hospital, ID,
Nantes, France.
Introduction: NEAT001/ANRS143 was an open-label, randomized, non-inferiority study comparing raltegravirdarunavir/r
(RGVDRV/r) vs. tenofovir/emtricitabinedarunavir/r (TDF/
FTC DRV/r) in HIV-infected antiretroviral naı̈ve adults.
Primary efficacy outcome was a composite of virological and
clinical events by week 96.
Materials and Methods: Clinical trial units collected and
translated supporting documentation (SD) related to the
investigator-reported events. A coordinator checked events
and SD for consistency and completeness. The Endpoint
Abstract P039Figure 1. Factors associated with risk of stopping TDF. Adjusted RH from fitting a Cox regression model. Model also adjusted
for: age, gender, mode of HIV transmission, HCV status, AIDS diagnosis, CD4 and VL at time of starting TDF nadir CD4 count, nationality,
diabetes and use of blood pressure lowering drugs. Only factors with p B0.1 shown in graph.
57
Poster Abstracts
Review Committee (ERC) determined if clinical events met
pre-defined diagnostic criteria in categories ‘‘confirmed’’ or
‘‘probable’’. The ERC of 12 experienced, independent clinicians
served in groups of three conducting individual reviews in
writing, blinded to treatment arm. Differences of opinion were
adjudicated in a second review by direct dialogue between
reviewers. ‘‘Confirmed’’ events required adequate SD like
laboratory, radiographic or pathology diagnostic reports.
‘‘Probable’’ events were typically based on clinical criteria.
Results: Of the 164 serious and 3,964 adverse events
reported in the study, 133 qualified for endpoint review, for
a total of 153 adjudications:
Sixty of 111 per protocol endpoints were confirmed (n 53) or
probable (n 7), which equals an acceptance rate of 54%. In
two confirmed cases, SD was partly adequate and evaluation
uncertain. Of 51 rejected events, 13 had insufficient SD, two
were recurrent events. The rate of rejected events was
comparable between treatments with 41% rejected events
in the RGVDRV/r arm compared to 52% in the TDF/
FTCDRV/r arm. The IRIS acceptance rate was low (3 of 18),
demonstrating the difference in perception of IRIS in daily
patient management and the stricter protocol definition.
Conclusions: Blinded endpoint review prevented unacceptably high false positive event rates documenting that real-time
ascertainment of clinical endpoints is crucial for appropriateness of the overall results. Non-confirmed events jeopardize
the statistical power in this and probably all kinds of clinical
studies. The rejection rate was not indicative of poor study
conduct on the contrary over-reporting prevented missing
events, which would have adversely impacted the trial.
Adequacy of SD and investigator training on possible differences in event criteria in daily pragmatic clinical management
compared to protocol defined criteria is essential.
P041
Safety of darunavir/ritonavir (DRV/r) in HIV-1-infected DRV/
r-experienced and -naı̈ve patients: analysis of data in the
real-world setting in Italy
Andrea Antinori1; Marco Borderi2; Roberto Cauda3; Teresa Bini4;
Antonio Chirianni5; Nicola Squillace6; Daniela Mancusi7 and
Roberta Termini7
1
Clinical Department, National Institute for Infectious Diseases
‘‘L Spallanzani’’, Rome, Italy. 2Department of Medical and Surgical
Sciences, Infectious Disease Unit, Alma Mater Studiorum, University
of Bologna, Bologna, Italy. 3Institute of Infectious Diseases, A.
Gemelli Hospital, Catholic University of the Sacred Heart, Rome, Italy.
4
Department of Medicine, Surgery and Dentistry, Clinic of Infectious
Diseases, San Paolo Hospital, Milan, Italy. 5Department of Infectious
Disease, Cotugno Hospital, Naples, Italy. 6Division of Infectious
Diseases, Department of Internal Medicine, San Gerardo Hospital,
Monza, Italy. 7Janssen SpA, Medical Affairs, Cologno Monzese,
Italy.
Introduction: This descriptive, non-interventional study on
HIV-1-infected patients treated with DRV/r in the usual
clinical setting, with a single-arm prospective observational
design, collected data on utilization of darunavir/ritonavir
(DRV/r) under the conditions described in marketing author-
Endpoint review results by type of endpoint
Clinical study
Clinical study
Clinical study
Clinical study
Clinical study
Clinical study
endpoint
endpoint
endpoint
endpoint
endpoint
endpoint
Rashes
All
AIDS
Serious
non-AIDS
IRIS
Clinical Grade
4 AE
Death
Rash
Total reviewed events
111
24
35
18
29
5
Per Protocol Endpoints
60
11
18
3
23
5
53
11
16
2
19
5
42
(confirmed probable)
Confirmed Events (for rashes:
grade 2-4)
SD* adequate
SD* sufficiently/only partly
28
42
10
11
1
16
4
6
10/1
1/0
5/0
0/1
3/0
1/0
19/3
adequate
Probable Events
7
0
2
15
4
0
-
6/1
0/0
2/0
2
4/0
0/0
-/-
Rejected Events (for rashes: grade
51
13
17
15
6
0
14
1 or not a rash)
Not fulfil criteria, SD* adequate
17
3
9
2
3
0
4
Not fulfil criteria, SD* sufficiently
21
8
3
8
2
0
5
13
2
5
5
1
0
5
SD* sufficiently/ only partly
adequate
adequate
Not fulfil criteria, SD* only partly
adequate
58
Poster Abstracts
ization in usual clinical practice in Italy to evaluate efficacy
and safety of DRV/r-based antiretroviral (ARV) treatment.
This analysis focussed on the safety profile of DRV/r in HIV-1
infected patients.
Materials and Methods: Data were analyzed from four
cohorts of HIV-1-infected patients treated with DRV/r in the
real-world setting, including an ARV-naı̈ve-DRV/r-naı̈ve cohort
(Cohort 1), an ARV-experienced-DRV/r-naı̈ve cohort (Cohort
2) and two ARV-DRV/r-experienced cohorts (Cohorts 3 and
4), one of which (Cohort 3) was from the DRV/r Early Access
Program. The objective of this analysis was to examine the
safety data obtained in these four cohorts in patients
enrolled from June 2009 to November 2011 and observed
until December 2012 or DRV/r discontinuation.
Results: Safety data from 875 patients were analyzed. DRV/rbased treatment was well tolerated, with 36.2% of patients
reporting ]1 adverse event (AE) and very few discontinuations due to study drug-related AEs (3.0% overall). The most
frequent AEs were diarrhoea (2.7%), reduced bone density
(2.6%) and hypercholesterolaemia (2.1%) (Table 1). Regarding
metabolic parameters, levels of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
remained stable from baseline to the last study visit (LSV) in
DRV-experienced patients and decreased in DRV-naı̈ve patients. Blood glucose concentrations remained stable in all
cohorts. Serum triglyceride and cholesterol concentrations
remained stable in DRV-experienced patients but increased in
naı̈ve patients, yet were still within normal range.
Conclusions: In HIV-1-infected patients treated with DRV/r in
these settings, the tolerability profile was favourable and
similar to (or better than) that reported in controlled clinical
trials. These data confirm DRV/r to be a safe treatment choice
in DRV/r-experienced and naı̈ve patients.
P042
Efficacy and safety of etravirine-containing regimens in a
large cohort of HIV/HCV coinfected patients according to
liver fibrosis
Jose Luis Casado1; Alvaro Mena2; Sara Bañón1; Ana Moreno1;
Angeles Castro2; Marı́a J Perez-Elı́as1; JD Pedreira2 and
Santiago Moreno1
1
Infectious Diseases, Ramon y Cajal Hospital, Madrid, Spain. 2Internal
Medicine, Juan Canalejo, A Coruña, Spain.
Introduction: Etravirine has become an alternative in HIV/
HCV coinfected patients because of safety and lack of
interactions with anti-HCV drugs. The aim of this study was
to establish the risk of liver toxicity in HIV/HCV coinfected
patients receiving etravirine in the clinical setting, according
to the degree of liver fibrosis and different accompanying
drugs.
Material and Methods: Cohort study of 211 patients initiating etravirine as part of their antiretroviral regimen. HCV coinfection was defined as a positive RNA-HCV, whereas baseline
liver fibrosis was assessed by transient elastography at baseline. Hepatotoxicity was defined as an increased AST/ALT,
5-fold higher over upper, normal limits for patients with
normal baseline values, or 3.5-fold if altered at baseline.
Results: HCV coinfection was observed in 145 patients (69%)
with a longer time of HIV infection and time on HAART than
mono-infected patients, and a lower nadir (182 vs 227 cells/
mL; p0.02) and baseline CD4 count (446 vs 552 cells/mL;
p0.02). Etravirine was used with two nucleoside analogues
in 62%, with boosted darunavir in 17%, with raltegravir in
10%, and with darunavir plus raltegravir or maraviroc in 10%
of patients without differences according to HCV serostatus.
Transient elastography in 117 patients performed at etravirine initiation (median, 33 days) showed fibrosis 1 and fibrosis
4 in 37% and 24% of cases, and median stiffness value was
Adverse events
All patients
Cohort 1
Cohort 2
Cohort 3
Cohort 4
(N 875); N (%)
(N 117); N (%)
(N 116); N (%)
(N 235); N (%)
(N 407); N (%)
317 (36.2)
47 (40.2)
54 (46.6)
107 (45.5)
108 (26.5)
39 (4.5)
12 (10.3)
8 (6.9)
9 (3.8)
10 (2.5)
105 (12.0)
19 (16.2)
16 (13.8)
26 (11.1)
43 (10.6)
Death
26 (3.0)
3 (2.6)
4 (3.4)
10 (4.3)
9 (2.2)
Darunavir treatment stopped
because of AEs
26 (3.0)
8 (6.8)
6 (5.2)
3 (1.3)
9 (2.2)
Rash
10 (1.1)
4 (3.4)
4 (3.4)
2 (0.9)
0
Diarrhoea
24 (2.7)
3 (2.6)
4 (3.4)
8 (3.4)
9 (2.2)
Hypertension
15 (1.7)
1 (0.9)
2 (1.7)
10 (4.3)
2 (0.5)
Hepatic enzymes increased
10 (1.1)
4 (3.4)
1 (0.9)
3 (1.3)
2 (0.5)
Hypercholesterolaemia
18 (2.1)
2 (1.7)
2 (1.7)
8 (3.4)
6 (1.5)
Hypertriglyceridemia
Hyperlipaemia
15 (1.7)
11 (1.3)
1 (0.9)
5 (4.3)
3 (2.5)
1 (0.9)
6 (2.6)
2 (0.9)
5 (1.2)
3 (0.7)
AEs
One or more AEs
One or more ADRs
One or more serious AEs
AE Description
Reduced Bone Mineral Density
23 (2.6)
1 (0.9)
3 (2.6)
10 (4.3)
9 (2.2)
Fever
14 (1.6)
6 (5.1)
0
5 (2.1)
3 (0.7)
59
8.25 kPa (3.569). During an accumulated follow-up of 449.3
patient-years (median, 611 days), only one coinfected patient
with fibrosis 4 (stiffness value, 50.1 kPa), receiving a rescue
regimen including darunavir/r plus maraviroc plus two
nucleoside analogues, developed a grade 3-4 of liver toxicity
(0.5%). There were no other episodes of liver toxicity, as
defined, and only 6 (3%) and 9 patients (4%) had a grade 1
and 2 of toxicity, respectively, in most cases related to HCV
coinfection (6 and 6 cases). Moreover, HCV coinfection or
advanced fibrosis was not associated to a higher risk of
etravirine discontinuation (26% vs 21%; p 0.27, log-rank
test) or virologic failure (9% vs 11%, p0.56). CD4 cell
count increase was lower in HCV patients (23 vs 86 at 6
month; p0.02).
Conclusions: Etravirine is safe in HIV/HCV coinfected patients,
even in presence of moderate and advanced liver fibrosis and
as part of different antiretroviral regimens.
P043
Sex differences in apolipoprotein A1 and nevirapineinduced toxicity
Aline Marinho1; Clara Dias1; Alexandra Antunes2; Umbelina Caixas3;
Teresa Branco4; Matilde Marques2; Emı́lia Monteiro1 and
Soa Pereira1
1
Centro de Estudos de Doenças Crónicas (CEDOC), Faculdade de
Ciências Médicas, Universidade NOVA, Lisbon, Portugal. 2Centro de
Quı́mica Estrutural, Instituto Superior Técnico (CQE-IST),
Universidade de Lisboa, Lisbon, Portugal. 3Centro Hospitalar de
Lisboa Central (CHLC), Lisbon, Portugal. 4Hospital Prof. Doutor
Fernando Fonseca, Lisbon, Portugal.
Nevirapine (NVP) is associated with severe liver and skin
toxicity through sulfotransferase (SULT) bioactivation of the
phase I metabolite 12-hydroxy-NVP [13]. The female sex, a
well-known risk factor for NVP-induced toxicity, is associated
with higher SULT expression [4] and lower plasma levels of 12hydroxy-NVP [3]. Interestingly, apolipoprotein A1 (ApoA1)
increases SULT2B1 activity and ApoA1 synthesis is increased
by NVP [5,6]. Herein, we explore the effect of ApoA1 levels on
NVP metabolism and liver function. The study protocol was
firstly approved by the hospitals’ Ethics Committees. All
included individuals were HIV-infected patients treated with
NVP for at least one month. The plasma concentrations of
NVP and its phase I metabolites were quantified by HPLC [7].
ApoA1 levels were assessed by an immunoturbidimetric
assay. Forty-nine HIV-infected patients on NVP were included
(53% men, 59% Caucasian). NVP plasma levels were correlated with HDL-cholesterol (Spearman r 0.2631; p0.0441)
and ApoA1 (Spearman r0.3907; p0.0115). Women had
higher ApoA1 levels than men (Student’s t Test; p 0.0051).
In both sexes, 12-hydroxy-NVP levels were negatively correlated with ApoA1 (male: Spearman r 0.3810; p0.0499
female: Spearman r 0.5944; p0.0415). In men, ApoA1
was positively correlated with aspartate aminotransferase
(AST, Spearman r0.5507; p0.0413), while in women
ApoA1 was associated (Spearman r 0.6408; p0.0056)
with alanine aminotransferase (ALT). These results show sex
differences in NVP-induced ApoA1 synthesis. The higher
Poster Abstracts
ApoA1 levels in women might stabilize SULT2B1 [6]. This
would explain the lower levels of 12-hydroxy-NVP [3] and the
higher hepatotoxicity found in women, due to increased
sulfonation of this metabolite. These data support a role for
ApoA1 in the sex dimorphic mechanism leading to NVPinduced toxicity.
Acknowledgments: RECI/QEQ-MED/0330/2012; PTDC/SAUTOX/111663/2009; EXPL/DTP-FTO/0204/2012.
References
1. Antunes AM, Godinho AL, Martins IL, Justino GC, Beland FA,
Marques MM. Amino acid adduct formation by the nevirapine
metabolite, 12-hydroxynevirapine a possible factor in nevirapine
toxicity. Chem Res Toxicol. 2010 May 17;23(5):88899.
2. Caixas U, Antunes AM, Marinho AT, et al. Evidence for nevirapine
bioactivation in man: searching for the first step in the mechanism of
nevirapine toxicity. Toxicology. 2012 Nov 15;301(13):339.
3. Marinho AT, Rodrigues PM, Caixas U, et al. Differences in
nevirapine biotransformation as a factor for its sex-dependent
dimorphic profile of adverse drug reactions. J Antimicrob Chemother.
2014 Feb;69(2):47682.
4. Alnouti Y, Klaassen CD. Tissue distribution and ontogeny of
sulfotransferase enzymes in mice. Toxicol. Sci. 2006 Oct;93(2):
24255.
5. Franssen R, Sankatsing RR, Hassink E, et al. Nevirapine increases
high-density lipoprotein cholesterol concentration by stimulation of
apolipoprotein A-I production. Arterioscler Thromb Vasc Biol. 2009
Sep;29(9):133641.
6. Yanai H, Javitt NB, Higashi Y, et al. Expression of cholesterol
sulfotransferase (SULT2B1b) in human platelets. Circulation. 2004 Jan
6;109(1):926.
7. Marinho AT, Godinho ALA, Novais DA, et al. Development and
validation of an HPLC-UV method for quantifying nevirapine and
its main phase I metabolites in human blood. Anal. Methods.
2014;6:157580.
P044
Prevalence and risk factors of sleep disturbances in a large
HIV-infected adult population
Clotilde Allavena1; Thomas Guimard2; Eric Billaud3; Sylvie de la
Tullaye4; Véronique Reliquet1; Solène Pineau3; Hervé Hüe3;
Christelle Supiot1; Jean Marie Chennebault5; Christophe Michau6;
Hikombo Hitoto7; Rémi Vatan8 and François Raf1
1
Infectious Diseases, CHU Hôtel-Dieu, Nantes, France. 2Infectious
Diseases, CHD Vendée, La Roche sur Yon, France. 3Infectious
Diseases, CHU Hôtel-Dieu, COREVIH Pays de la Loire, Nantes, France.
4
CHU, Explorations Fonctionnelles, Nantes, France. 5Infectious
Diseases, CHU, Angers, France. 6CH, Médecine, St Nazaire, France.
7
Infectious Diseases, CH, Le Mans, France. 8Médecine Interne, CH,
Laval, France.
Introduction: Sleep disturbances are frequently reported in
HIV-infected patients but there is a lack of large studies on
prevalence and risk factors, particularly in the context of
current improved immuno-clinical status and use of the
newest antiretrovirals (ARV).
Method: Cross-sectional study to evaluate the prevalence
and factors associated with sleep disturbance in adult HIVinfected patients in six French centres of the region ‘‘Pays de
la Loire’’. Patients filled a self-administered questionnaire on
their health behaviour, sleep attitudes (Pittsburgh Sleep
60
Quality Index PSQI), quality of life (WHO QOL HIV BREF
questionnaire) and depression (Beck depression Inventory
(BDI)-II questionnaire). Socio-demographic and immunovirologic data, medical history, ARVs were collected.
Results: From November 2012 to May 2013, 1354 consecutive
non-selected patients were enrolled. Patients’ characteristics
were: 73.5% male, median age 47 years, active employment
56.7%, France-native 83% and Africa-native 14.7%, CDC
stage C 21%, hepatitis co-infection 13%, lipodystrophy
11.8%, dyslipidemia 20%, high BP 15.1%, diabetes 3%,
tobacco smokers 39%, marijuana and cocaine users, 11.7%
and 1.7% respectively, and excessive alcohol drinkers 9%.
Median (med) duration of HIV infection was 12.4 years, med
CD4 count was 604/mm3; 94% of Patients were on ARVs, 87%
had undetectable viral load. Median sleeping time was 7
hours. Sleep disturbances (defined as PSQI score 5) were
observed in 47% of the patients, more frequently in female
(56.4%) than in male (43.9%) (p B0.05) and moderate to
serious depressive symptoms (BDI score19) in 19.7% of the
patients. In multivariate analysis, factors associated with sleep
disturbances (p B0.05) were depression (odds ratio [OR] 4.6;
95% confidence interval [CI] 3.26.8), male gender (OR 0.7;
CI 0.50.9), active employment (OR 0.7; CI 0.50.9), living
single (OR 1.5; CI 1.22.0), tobacco-smoking (OR 1.3; CI 1.0
1.8), duration of HIV infection ( 10 vs. B10 y.) (OR 1.5;
CI 1.12.0), ARV regimen containing nevirapine (OR 0.7;
CI 0.50.9) or efavirenz (OR 0.5; CI 0.30.7).
Conclusions: Prevalence of sleep disturbances is high in this
HIV population and roughly similar to the French population.
Associated factors are rather related to social and psychological status than HIV infection. Depression is frequent and
should be taken in care to improve sleep quality.
Poster Abstracts
answer the clinically relevant question of whether magnetic
resonance spectroscopy can detect changes in the cerebral
metabolism of asymptomatic HIV-positive patients and is
possibly suitable for the early diagnosis and prevention of HIV
encephalopathy.
Methods: A group of 13 asymptomatic, HIV-positive patients
with combined antiretroviral therapy (cART) and 13 healthy
controls were examined with 2D 1H-MRS and 3D 31P-MRS at
3T. The patients were treated with cART for at least 12
months. Changes in the absolute concentrations of phosphorylated metabolites (ATP), N-acetyl-aspartate, creatine,
myo-Isonitol, glutamate/glutamine and choline-containing
compounds were compared with that of control subjects.
Results: Asymptomatic HIV-positive patients had significantly
lower N-acetyl-aspartate in the white matter in a frontal and
parietal target region. The other evaluated metabolites in the
1H MRS showed no significant difference between the HIVpositive patients and healthy controls. The 31P-MRS detected
significant elevated values regarding the choline-containing
compounds PEth, GPE and PCho.
Conclusions: This spectroscopic study revealed a significantly
lower N-acetyl-aspartate in the white matter in a frontal and
parietal cerebral target region in asymptomatic, HIV-positive
patients as an early sign of neuronal disintegration. The 31PMRS detected significant elevated values regarding the
choline-containing compounds PEth, GPE and PCho as an
early sign of gliosis. Furthermore we could show that with
the use of 1H-MRS and 31P-MRS cerebral metabolites can be
reliably detected and measured in HIV-positive patients. The
1H-MRS and 31P-MRS is therefore suited as a diagnostic
tool for early cerebral metabolic changes in HIV-positive
patients.
P045
Proton 1H- and Phosphorus 31P-MR spectroscopy (MRS) in
asymptomatic HIV-positive patients
Gundolf Schuettfort1; Elke Hattingen2; Ulrich Pilatus2;
Christoph Stephan1; Timo Wolf1; Siri Goepel1; Annette Haberl1;
Stella Blasel2; Freidhelm Zanella2; Hans-Reinhard Brodt1 and
Markus Bickel3
1
University Hospital Frankfurt, Infectious Diseases / ZIM II, Frankfurt
am Main, Germany. 2University Hospital Frankfurt, Neuroradiology,
Frankfurt am Main, Germany. 3Infektiologikum Frankfurt, Infectious
Diseases / HIV-Therapy, Frankfurt am Main, Germany.
Introduction: HIV infection is accompanied by a variety of
neurological disorders. Depression of cell-mediated immunity
is followed by the development of central nervous system
opportunistic infections/tumours, and frequently by the
occurrence of the AIDS dementia complex (ADC). However,
the pathophysiology of the emergence of neuro-AIDS is still
unknown. Despite the development of cognitive impairments,
the early diagnosis, objectification and quantification of the
existence and extent of this impairment during infection are
difficult to recognize in each individual case. To support the
early diagnosis of ADC, there is a need for additional, noninvasive diagnostic methods. In this study, it is of interest to
P046
Cerebral volumes, neuronal integrity and brain
inflammation measured by MRI in patients receiving PI
monotherapy or triple therapy
Ignacio Pérez Valero1; Alicia Gonzalez Baeza1; Juan Antonio
Hernandez-Tamames2; Susana Monge3; Francisco Arnalich1 and
Jose Ramon Arribas1
1
Internal Medicine, H.U. La Paz, Madrid, Spain. 2Electronic
Department, Universidad Rey Juan Carlos, Madrid, Spain. 3Instituto
de Salud Carlos III, Centro Nacional de Epidemiologı́a, Madrid
Spain.
Introduction: Penetration of protease inhibitors (PI) in the
central nervous system (CNS) is limited. Therefore, there are
concerns about the capacity of PI monotherapy (MT) to
control HIV in CNS and preserve brain integrity.
Methods: Exploratory case-control study designed to compare
neuronal integrity and brain inflammation in HIV-suppressed
patients (2 years) with and without neurocognitive impairment (NI), treated with MT or triple therapy (TT), 3-Tesla
cerebral magnetic resonance image (MRI) and spectroscopy
(MRS) were used to evaluate neuronal integrity (volume of
cerebral structures and MRS levels of N-acetyl-aspartate
(NAA)) and brain inflammation (MRS levels of myo-inositol
(MI) and choline (CHO)). MRS biomarkers were measured in 4
61
Poster Abstracts
voxels located in basal ganglia, frontal (2) and parietal lobes. A
comprehensive battery of tests (14 tests - 7 domains) was used
to diagnose neurocognitive impairment [1].
Results: We included 18 neurocognitively impaired patients
(MT: 10, TT: 8) and 21 without NI (MT: 9; TT: 12, Table 1). Subset
of patients with NI: cerebral volumes and MRS biomarkers
were mostly similar between MT and TT with exception of the
right cingulate nucleolus volume (MT: 885491851 vs TT:
1048291107 mm3; pB0.04), CHO levels in basal ganglia (MT:
0.4490.05 vs TT: 0.3790.03 MMOL/L; pB0.01) and the NAA
levels in parietal lobe (MT: 1.4990.12 vs 1.7090.13 MMOL/L;
pB0.01). Subset of patients without NI: cerebral volumes and
MRS biomarkers were mostly similar between MT and TT with
exception of MI levels in frontal lobe (MT: 1.2090.36 vs
0.8190.25 MMOL/L; p0.01).
Conclusions: We did not find significant differences in cerebral
volumes or MRS biomarkers in most areas of the brain.
However, we found higher levels of inflammation and neuronal
damage in some brain areas of patients who received MT. This
observation has to be taken into caution while we could not
adjust our results by potential confounders. Further investigation is needed to confirm these preliminary results.
Reference
1. Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M,
et al. Updated research nosology for HIV-associated neurocognitive
disorders. Neurology. 2007;69(18):178999.
P047
Clinical significance of the UGT1A1*28 allele detection in
HIV-infected patients
Veronika Kanestri1; Konstantin Mironov2; Alexey Kravchenko1;
Anastasiya Pokrovskaya1; Olga Dribnohodova2; Elena Dunayeva2;
Galina Tsiganova1; Marina Harbutly1; Marina Goliusova1;
Vladislav Konnov1; Nadezhda Kozirina1; Vasiliy Shahgildyan1;
Ulyana Kuimova1; Anna Popova1; Oksana Efremova1 and
Danila Konnov1
1
Central Scientific Research Institute of Epidemiology, Russian AIDS
Federal Center, Moscow, Russian Federation. 2Department of Genetic
Polimorphisms, Central Scientific Research Institute of Epidemiology,
Moscow, Russian Federation.
Introduction: The UGT1A1*28 (rs8175347) polymorphism is
associated with hyperbilirubinemia. The presence of 6 TArepeats in the UGT1A1 gene promoter region corresponds to
normal UGT1TA1 activity. A detection of 7 TA-repeats in
hetero- or homozygous individuals [(TA)6/(TA)7 and (TA)7/
(TA)7] is associated with lower UGT1TA1 activity, which may
eventually result in the development of Gilbert syndrome and/
or modified individual response to drugs metabolized by this
enzyme. ATV contributes to the decreased levels of UGT1A1,
which may lead to elevations of indirect bilirubin, jaundice and
even to therapy discontinuation. We evaluated the prevalence
of the UGT1A1*28 among HIV-infected patients and the
dependence of the frequency and severity of AE during ATV
treatment on individual genetic characteristics.
Materials and Methods: 47 HIV-infected patients was screen
for UGT1A1 genotype and the presence of UGT1A1*28. All
patients received ATV in the HAART regimen for 48 weeks.
Changes in the total, direct and indirect bilirubin, ALT, AST,
GGT and jaundice were evaluated. Statistical analysis was
performed using Microsoft Office Excel for Windows XP
Professional 2007 and Biostat.
Results: All patients were followed up in the AIDS Center
(males 72.3%, median age 33 years, median CD4 count-282
cells/ml (19.5%). HBV/HCV was in 36.2% patients. Ten patients
had risk factors that could affect bilirubin turnover (chronic
cholecystitis, biliary dyskinesia, etc.). Genotype (TA)6/(TA)6
was found in 42.6% patients, (TA)6/(TA)7-42.6% and (TA)7/
(TA)7-14.9%. Overall prevalence of UGT1A1*28 was 57.4%,
and homozygous allele frequency was 14.9%. G3/4 of indirect
bilirubin were detected in 36.2% patients [(TA)6/(TA)6 in 10
20%, (TA)6/(TA)7-25-40%, (TA)7/(TA)7-72-86%], and significant jaundice in 10.6% [80% with (TA)7/(TA)7]. The OR for
hyperbilirubinemia 40 mmol/L in patients with heterozygous UGT1A1*28 was increased 3 times over patients
without this allele (OR 3.07, 95% CI 1.544.6) and 34 times
as compared with homozygotes (OR 33.9, 95% CI 31.45
36.35). The presence of additional risk factors increased
Main baseline characteristics by presence of neurocognitive impairment and type of antiretroviral therapy
Impaired cognitive functioning
Age, mean (DS)
Gender: male, n (%)
Normal cognitive functioning
p value
Monotherapy n 9
Triple therapy n 12
40.198.0
0.03
48.699.2
46.693.4
0.49
5 (62.5)
0.60
7 (77.8)
8 (66.7)
0.57
Monotherapy n10
Triple therapy n8
49.598.6
5 (50)
p value
HCV antibody , n (%)
3 (30)
2 (25)
0.53
4 (44.4)
4 (33.3)
0.67
CD4 nadir, median (IQR)
210 (71323)
73.5 (14221)
0.17
204 (187309)
178 (59284)
0.08
15.6 (12.917.9)
9.9 (4.620.5)
0.18
16 (13.222.3)
14.9 (8.620.9)
0.45
Time of HIV-suppression,
9.1 (6.311.2)
3.4 (35.6)
0.01
5.5 (4.411)
7.1 (4.611.4)
0.73
median (IQR)
Time on antiretroviral
13.2 (1215)
5.9 (3.813.9)
0.01
12.7 (7.216.7)
10.3 (6.316.5)
0.73
Time since HIV, median
(IQR)
therapy, median (IQR)
62
the probability of G3/4 hyperbilirubinemia. No significant
changes in the ALT, AST, and GGT levels were observed.
Conclusions: The risk of severe hyperbilirubinemia during ATV
treatment is minimal for patients without UGT1A1*28 and no
more than one additional risk factor and for patients with
UGT1A1*28 and no additional risk factors; patients with
homozygous genotype UGT1A1*28 are at the highest risk.
References
1. Phillips EJ, Mallal SA. Pharmacogenetics and the potential for the
individualization of antiretroviral therapy. Curr Opin Infect Dis.
2008;21(1):1624.
2. Rotger M, Taffe P, Bleiber G, Gunthard HF, Furrer H, Vernazza P,
et al. Gilbert syndrome and the development of antiretroviral
therapy-associated hyperbilirubinemia. J Infect Dis. 2005;192(8):
13816.
3. Park WB, Choe PG, Song KH. Genetic factors influencing severe
atazanavir-associated hyperbilirubinemia in a population with low
UDPglucuronosyltransferase 1A1*28 allele frequency. Clin Infect Dis.
2010;51(1):1016.
P048
Safety of rilpivirine plus nucleoside reverse-transcriptase
inhibitors in HIV-infected Taiwanese with a higher
prevalence of hepatitis virus infection
Pei-Ying Wu1; Chien-Yu Cheng2; Yu-Zhen Luo1; Jun-Yu Zhang1;
Shan-Ping Yang1; Shu-Hsing Cheng2 and Chien-Ching Hung3
1
Center for Infection Control, National Taiwan University Hospital,
Taipei city, Taiwan. 2Internal Medicine, Tao-Yuan General Hospital,
Tao-Yuan city, Taiwan. 3Internal Medicine, National Taiwan University
Hospital, Taipei city, Taiwan.
Introduction: Combination antiretroviral therapy (cART) containing rilpivirine plus 2 NRTIs are effective antiretroviral
(ARV) regimens for ARV-naive HIV-infected patients who had
baseline plasma HIV RNA load (PVL) B5 log10 copies/mL and
as switch therapy for those with viral suppression. In this
study, we aimed to assess the short-term safety of rilpivirinecontaining regimens among HIV-infected patients who initiated or switched to rilpivirine plus two NRTIs in Taiwan.
Materials and Methods: Between January and June 2014,
medical records of all HIV-infected patients who initiated or
switched to rilpivirine plus two NRTIs, during the follow-up
were reviewed to assess the tolerance and adverse effects.
Using a standardized data collection form, we recorded data
of PVL and CD4 count, serologies for hepatitis B and C virus
(HBV and HCV, respectively), haemogram, aminotransferases,
bilirubin and serum creatinine before starting rilpivirinecontaining regimens at four weeks and every 12 weeks
thereafter.
Results: During the study period, medical records of 246
patients initiated their first ARV therapy with rilpivirinecontaining regimens (n 90) or switched to rilpivirinecontaining regimen from other regimens (156). Of the 246
patients, 73.4% were men who have sex with men and 9.1%
and 25.6% tested positive for HBsAg and anti-HCV antibody,
respectively. Baseline CD4 was 395 cells/mm3 (range, 2-1581)
and PVL, 2.76 log10 copies/mL (range, B1.37.0 log10
copies/mL). As of 10 July, 23 patients (9.3%) stopped
rilpivirine-containing regimens due to gastrointestinal upset
Poster Abstracts
(n 4), skin rash (2), depression (2), poor sleep (3), anaemia
(4, all being with zidovudine/lamivudine), nail hyperpigmentation (1), presence of transmitted drug resistance (4), and
elevated aminotransferase levels (1). The proportion of the
patients with aminotransferases of fivefold or higher than the
upper limit of normal (ULN) was 1.7% and 1.5% for AST and
ALT, respectively, before starting rilpivirine-containing regimens; the respective value was 1.4% and 2.4% after 12 weeks
of cART.
Conclusions: Rilpivirine-containing regimens were generally
well tolerated and less than 10% of the patients had to stop
rilpivirine due to various reasons. Despite a higher prevalence
of chronic HBV or HCV infection, rilpivirine-containing regimens did not cause significant changes of aminotransferases
from baseline.
P049
Quality of life of people living with HIV, preliminary results
from IANUA (Investigation on Antiretroviral Therapy) study
Alberto Venturini1; Barbara Giannini2; Marcello Montefiori3;
Antonio Di Biagio4; Giovanni Mazzarello4; Giovanni Cenderello1;
Mauro Giacomini5; Caterina Merlano6; Patrizia Orcamo6;
Maurizio Setti7; Claudio Viscoli4 and Giovanni Cassola1
1
EO Ospedali Galliera, SC Infectious Diseases, Genova, Italy.
2
Università di Genova, Dipartimento di Informatica, Bioingeneria,
Robotica, Genova, Italy. 3Università di Genova, Dipartimento di
Economia, Genova, Italy. 4IRCCS AOU San Martino-IST, Clinica
Malattie Infettive, Università di Genova, Genova, Italy. 5Università
degli Studi di Genova, Dipartimento di Informatica, Bioingeneria,
Robotica, Genova, Italy. 6Regione Liguria, Agenzia Regionale
Sanitaria, Genova, Italy. 7IRCCS AOU San Martino-IST, Clinica di
Medicina Interna ad Orientamento Immuno, Genova, Italy.
Introduction: The introduction of combined antiretroviral
treatment (cART) has reduced HIV-associated morbidity and
mortality, and changed the patients’ perspective of life. As a
result, Health Related Quality of Life (HRQOL) has become a
crucial clinical issue.
Objective: Assessment of HRQOL in a sample of Italian
patients from IANUA study. Investigate correlation between
CD4 cell counts, viral load and changes in HRQOL.
Materials and Methods: EQ-5D-3L self-reported questionnaire has been used in the evaluation of HRQOL. It assesses
five dimensions: ‘‘mobility,’’ ‘‘self care,’’ ‘‘usual activities,’’
‘‘pain/discomfort’’ and ‘‘anxiety/depression.’’ Each dimension
has three levels: no problems, some problems and extreme
problems. In addition, it includes a Visual Analogue Scale
(VAS) where one’s own health ‘‘today’’ is rated from 0 ‘‘worst
imaginable health’’ to 100 ‘‘best imaginable health.’’ The
respondents provide information on marital status, education, employment/unemployment, other treatments used in
addition to HAART (1,2,3,4,5 or more) and number of
hospitalizations due to HIV/AIDS.
Results: 684 patients completed the questionnaire: 231
females and 453 males. The mean age of the sample was
51 years (range 21-78). The mean VAS score was 69.9. 558
patients (81.5%) reported no problems in mobility. 642
patients (93.5%) had no problems in self care. 423 patients
(61.8%) had no pain/discomfort while 219 had some
63
Poster Abstracts
problems. 326 patients (46.1%) had some problems in
anxiety/depression.
Conclusions: The analysis of self-reported questionnaires
indicates that HRQOL in our sample group is not deeply
affected by HIV/AIDS. The dimensions that are affected in the
least are ‘‘mobility’’ and ‘‘self care’’ while the major problem
is ‘‘anxiety/depression’’ with half of the sample reporting
moderate or high level.
Parameter
CSF 7OH-efavirenz
CLINICAL PHARMACOLOGY
P050
Cerebrospinal-fluid exposure of efavirenz and its major
metabolites when dosed at 400 and 600 mg once daily; a
randomized controlled trial
2
Geometric
means (ng/mL)
CSF efavirenz
1
Abstract P050Table 1. CSF geometric means and ratios of
efavirenz and metabolite concentrations by randomized arm
(Ratios are 400/600 mg)
CSF 8-OH-efavirenz
Arm
Mean
90% CI
(lower)
90% CI
(upper)
400 mg
16.4
13.0
20.7
600 mg
19.5
15.1
25.1
ratio
0.84
0.61
1.18
400 mg
0.62
0.41
0.93
600 mg
0.63
0.40
0.99
ratio
0.98
0.55
1.79
400 mg
600 mg
5.08
3.08
4.0
2.13
6.44
4.43
ratio
1.65
1.09
2.5
2
Alan Winston ; Rebekah Puls and CSF Sub-study group Encore
1
Department of Medicine, Imperial College London, London, UK.
2
Kirby Institute, TVRP, Sydney, Australia.
Introduction: The optimal penetration of antiretroviral
agents into central nervous system (CNS) may be a balance
between providing adequate drug exposure to inhibit HIVreplication whilst avoiding concentrations associated with
toxicities.
Methods: Cerebrospinal-fluid (CSF) exposure of efavirenz and
metabolites 7-hydroxy (7OH-) and 8OH-efavirenz were assessed after at least 12 weeks of antiretroviral therapy in HIVinfected subjects randomized to commence antiretroviral
regimens containing efavirenz at either 400 mg or 600 mg
once daily. Clinical, pharmacokinetic and pharmacogenomic
factors associated with CSF efavirenz and its metabolite
concentrations were assessed.
Results: Of 28 subjects who completed all study procedures
(14/14 on efavirenz 400mg/600mg), CSF HIV RNA was below
20 copies/mL in all at the time of examination. Concentrations of efavirenz and 7OH-efavirenz in the CSF were slightly
lower when dosed at 400mg versus 600mg, although this was
not statistically significant. A different trend was observed
regarding 8OH-efavirenz concentrations where CSF exposure
was slightly increased in the 400 mg efavirenz arm (see
Table). Efavirenz concentration in the CSF was above 0.51 ng/mL
(proposed CSF IC50 for WT virus) in all subjects and 8OHefavirenz concentration in the CSF was above 3.3 ng/mL (a
proposed toxicity threshold, reference) in 11/14 and 7/14
subjects randomized to the 400 mg and 600 mg doses of
efavirenz, respectively. Whilst CSF efavirenz concentration
was significantly associated with plasma concentration
(PB0.001) and CYP2B6 genotype (CSF efavirenz GG to GT/
TT GM ratio 0.56, 90% CI 0.420.74), CSF 8OH-efavirenz
concentration was not (P0.242 for association with plasma
concentration and CSF 8OH-efavirenz GG to GT/TT GM ratio
1.52, 90% CI 0.972.36). Lastly, CSF 8OH-efavirenz concentration was associated with efavirenz symptom questionnaire
results at one year (Spearman’s correlation 0.13, P0.05).
Conclusions: With both doses of efavirenz studied, CSF
concentrations were considered adequate to inhibit HIVreplication, although concentrations of 8OH-efavirenz were
greater than that reportedly associated with neuronal
toxicity. CSF exposure of 8OH-efavirenz was not dependent
on plasma exposure and we postulate may be subject to
saturable pharmacokinetic effects.
Reference
1. Tovar-y-Romo LB, Bumpus NN, Pomerantz D, Avery LB, Sacktor N,
McArthur JC, et al. Dendritic spine injury induced by the 8-hydroxy
metabolite of efavirenz. J Pharmacol Exp Ther. 2012;343:696703.
P051
Should the dose of tenofovir be reduced to 200250mg/
day, when combined with protease inhibitors?
Andrew Hill1; Saye Khoo1; David Back1; Anton Pozniak2 and
Marta Boffito2
1
Pharmacology and Therapeutics, University of Liverpool, Liverpool,
UK. 2St Stephens Centre, Chelsea and Westminster Hospital, London,
UK.
Introduction: The approved dose of tenofovir disproxil
fumarate, 300mg once daily, was established in clinical trials
in combination with efavirenz, which does not significantly
affect tenofovir concentrations. Combining tenofovir with
lopinavir/r, darunavir/r or atazanavir/r increases tenofovir
concentrations, which could raise the risk of renal adverse
events. Newly approved tenofovir tablets are available at
lower strength (200 or 250mg) for use in paediatrics.
Methods: A literature search was used to assess the effects
of lopinavir/r, darunavir/r and atazanavir/r on tenofovir
plasma Cmax, AUC and Cmin (Geometric Mean Ratio and
90% confidence intervals). Assuming linear dose-proportional
pharmacokinetics (as observed in dose-ranging studies), the
250mg tablet was predicted to achieve plasma concentrations 17% lower than the 300mg dose, and the 200mg tablet
to achieve plasma levels 33% lower. Effects on tenofovir
plasma Cmax, AUC and Cmin concentrations were assessed
for combined dosing of each protease inhibitor with 250
or 200mg daily doses of tenofovir, versus standard dose
tenofovir (300mg daily) without protease inhibitors.
64
Results: In drug-drug interaction studies, lopinavir/ritonavir
significantly increased tenofovir Cmax, AUC and Cmin. Effects
of each PI on tenofovir Cmin were greater than effects
on Cmax or AUC. Using a 250 mg paediatric dose of tenofovir
with lopinavir/ritonavir, tenofovir Cmin was predicted to
remain higher than tenofovir 300 mg used with efavirenz
(GMR1.26, 95% CI 1.141.38). Similar results were observed for use of tenofovir 250 mg with atazanavir/ritonavir
(GMR1.07, 95% CI 1.011.13) and with darunavir/ritonavir
(GMR1.14, 95% CI 0.991.31). Predicted tenofovir AUC
levels for the 250 mg dose with protease inhibitors were all
within the bioequivalence range, relative to use with efavirenz.
Using a 200 mg paediatric dose of tenofovir with lopinavir/
ritonavir, the tenofovir Cmin was predicted to be bioequivalent
to tenofovir 300 mg used with efavirenz (GMR 1.02, 95%
CI 0.921.11). Similar results were observed for use of
tenofovir 200mg with atazanavir/ritonavir (GMR0.86, 95%
CI 0.820.91) and with darunavir/ritonavir (GMR0.92, 95%
CI 0.801.05). All three results were within the bioequivalence
limits of 0.81.25.
Conclusions: Use of approved paediatric doses of tenofovir
(200250 mg once daily) in combination with lopinavir/r,
darunavir/r or atazanavir/r could compensate for known drug
interactions. This dose modification could potentially improve
renal safety.
P052
The effect of dolutegravir on the pharmacokinetics of
metformin in healthy subjects
Jian Zong1; Julie Borland2; Fred Jerva2; Brian Wynne3;
Mike Choukour4 and Ivy Song1
1
Clinical Pharmacology Modeling & Simulation, GlaxoSmithKline, RTP,
USA. 2CPSSO, GlaxoSmithKline, RTP, USA. 3Infectious Disease MDD,
GlaxoSmithKline, RTP, USA. 4Biostatistics, Parexel, Sarasota, FL, USA.
Introduction: Dolutegravir (DTG) is an HIV integrase strand
transfer inhibitor approved for use in combination with
other antiretrovirals for the treatment of HIV-infection in
adults and adolescents. Metformin is a drug frequently
used in diabetic HIV-infected patients, which requires titration to optimize dosing. In vitro, DTG inhibits organic cation
transporter 2 (OCT2) and multidrug and toxin extrusion
transporter 1 (MATE 1) which are known to be involved in
the disposition of metformin. The objective of this study
Poster Abstracts
was to assess the drug interaction between DTG and
metformin.
Materials and Methods: This was an open-label, parallelgroup, three-period crossover study in healthy adult subjects.
Eligible subjects were enrolled into one of the two treatment
cohorts (15 subjects/cohort). Subjects received metformin
500 mg q12h for 5 days in Period 1; metformin 500 mg q12h
plus DTG 50 mg q24h (Cohort 1) or 50 mg q12h (Cohort 2) for
7 days in Period 2; and metformin 500 mg q12h for 10 days in
Period 3. There were no washout periods between treatments. All doses of study drug were taken with a moderatefat meal. Serial plasma PK samples and safety assessments
were obtained throughout the study. Non-compartmental PK
analysis was performed and geometric least squares (GLS)
mean ratios and 90% confidence intervals (CI) were generated
by the mixed effect model for within-subject treatment
comparisons for each cohort.
Results: Fourteen and thirteen subjects completed study in
Cohort 1 and Cohort 2, respectively. Plasma exposures of
metformin were significantly increased when co-administered
with DTG (Table 1).
There were no apparent changes in metformin half-life and
tmax. Increased metformin plasma exposure returned to
normal levels observed in Period 1 after DTG was discontinued in Period 3. No Grade 3 or 4 adverse events (AEs),
deaths or serious AEs were reported during the study. Most
frequently reported drug-related AEs were headache (9),
loose stools (8), and nausea (7). All AEs were mild or Grade 1
with the exception of one Grade 2 headache.
Conclusions: Co-administration of DTG and metformin was
well tolerated, yet significantly increased metformin plasma
exposure; effects were DTG dose dependent. Though metformin has a wide therapeutic index and alone is not
associated with hypoglycemia, close monitoring is recommended when co-administering metformin and DTG. Dose
adjustments of metformin may be considered.
P053
Low isoniazid and rifampicin concentrations in TB/HIV
co-infected patients in Uganda
Christine Sekaggya Wiltshire1; Mohammed Lamorde1;
Alexandra Scherrer2; Joseph Musaazi1; Natascia Corti3;
Buzibye Allan1; Rita Nakijoba1; Damalie Nalwanga1; Lars Henning2;
Statistical comparison of metformin PK parameters with and without dolutegravir
GLS mean
Plasma Metformin PK Parameter
GLS mean ratio (90% CI)
Metformin Alone (Period 1)
MetforminDTG (Period 2)
Cohort 1 (DTG 50 mg QD)
n15
n14
Cmax (mg/mL)
0.932
1.55
1.66 (1.53, 1.81)
AUC(0-t) (hr*mg/mL)
6.83
12.2
1.79 (1.65, 1.93)
n15
0.845
n14
1.878
2.11 (1.91, 2.33)
6.49
15.9
2.45 (2.25, 2.66)
Cohort 2 (DTG 50 mg BID)
Cmax (mg/mL)
AUC(0-t) (hr*mg/mL)
MetforminDTG vs. Metformin Alone
65
Amrei Von Braun1; Solome Okware1; Barbara Castelnuovo1;
Andrew Kambugu1 and Jan Fehr2
1
Infectious Diseases Institute, Research, Kampala, Uganda.
2
Infectious Disease and Hospital Epidemiology, University Hospital of
Zurich, Zurich, Switzerland. 3Clinical Pharmacology and Toxicology,
University Hospital of Zurich, Zurich, Switzerland.
Introduction: There is limited data available on exposure to
anti-tuberculosis (TB) drugs in this region. Peloquin has
described reference ranges [1] however some studies have
demonstrated that patients actually achieve concentrations
below these ranges [2]. There is limited data about exposure
to anti-TB drugs in the HIV/TB co-infected population in SubSaharan Africa. Our objective is to describe the concentration
of anti-TB drug levels in a well characterized prospective
cohort of adult patients starting treatment for pulmonary TB.
Methods: This study is an ongoing study carried out in the
TB/HIV integrated clinic at the Infectious Diseases Institute in
Kampala, Uganda. Sputum culture and microscopy was
done for all patients. We performed pharmacokinetic blood
sampling of anti-TB drugs for 1 hour, 2 hours and 4 hours
post dose at 2 weeks, 8 weeks and 24 weeks after initiation
of anti-TB treatment using ultraviolet high-performance
liquid chromatography (UV-HPLC). We described the maximum concentration (Cmax) of isoniazid (H), rifampicin (R),
ethambutol (E) and pyrazinamide (Z) and compare them with
the values observed by Peloquin et al referenced in other
studies.
Results: We started 113 HIV infected adults on a fixed dose
combination of HREZ. The median age of our population was
Poster Abstracts
33 years, of which 52% were male with a median BMI of 19
kg/m2 and a median CD4 cell count of 142 cells/mL. In 90% of
the participants, the diagnosis of TB was based on microscopy and or cultures. The boxplot graph shows the median
Cmax and IQR of H and R.
Levels of H were found to be below the reference ranges (36
mg/mL) in 54/77(70.1%), 38/59(64.4%) and 15/24(62.5%)
participants at weeks 2, 8 and 24. Rif levels were also found
to be below the reference ranges (824 mg/mL) in 41/
66(62.1%), 26/48(54.2%) and 8/10(8%) participants at weeks
2, 8 and 24, respectively. The mean Cmax of E and Z were
within the reference range at week 2 and 8; mean Cmax
of 3.29SD2.1 mg/mL and 4.09SD3.1 mg/mL for E and
41.69SD13.1 mg/mL and 42.69SD16.4 mg/mL for Z.
Conclusion: We observed lower concentrations of isoniazid
and rifampicin in our study population of HIV/TB co-infected
patients. The implications of these findings are not yet clear.
We therefore need to correlate our findings with the
response to TB treatment.
References
1. Peloquin CA. Therapeutic drug monitoring in the treatment of
tuberculosis. Drugs. 2002;62:216983.
2. Chideya S, Winston CA, Peloquin CA, Bradford WZ, Hopewell PC,
Wells CD, et al. Isoniazid, rifampin, ethambutol, and pyrazinamide
pharmacokinetics and treatment outcomes among a predominantly
HIV-infected cohort of adults with tuberculosis from Botswana. Clin
Infect Dis. 2009;48(12):168594.
Abstract P053Figure 1. Maximum drug concentrations in comparision to reference ranges.
66
Poster Abstracts
P054
Simulation of the impact of rifampicin on darunavir/
ritonavir PK and dose adjustment strategies in HIV-infected
patients: a population PK approach
Laura Dickinson1; Alan Winston2,3; Marta Boffito2,4; Saye Khoo1;
David Back1 and Marco Siccardi1
1
Department of Molecular & Clinical Pharmacology, University of
Liverpool, Liverpool, UK. 2Faculty of Medicine, Imperial College,
London, UK. 3Department of HIV & Genitourinary Medicine,
Imperial College Healthcare NHS Trust St Mary’s Hospital, London,
UK. 4St Stephen’s Centre, Chelsea & Westminster Foundation Trust,
London, UK.
Introduction: Treatment of HIV/TB co-infection is challenging
due to high drugdrug interaction potential between antiretrovirals and rifamycins, such as rifampicin (RIF). The PK
interaction between darunavir/ritonavir (DRV/RTV) and RIF
has not been studied. Utilizing other protease inhibitor data,
population PK modelling and simulation was applied to
assess the impact of RIF on DRV/RTV PK and generate
alternative dosing strategies to aid future clinical trial design.
Materials and Methods: A previously developed model
describing DRV/RTV PK including data from three studies in
HIV patients was used [n 51, 7 female, DRV/RTV 800/100 mg
(n 32) or 900/100 mg once daily (qd; n19) [1]. The PK
interaction between DRV/RTV and RIF was assumed to mimic
that observed in HIV-infected, TB negative patients receiving
lopinavir (LPV)/RTV (n 21) [2]. Simulations of DRV/RTV 800/
100 mg qd (n 1000) were performed (-RIF). The model was
adapted to increase the typical value of apparent oral
clearance (CL/F) by 71% and 36% and decrease relative bioavailability (F) by 20% and 45% for DRV and RTV, respectively
[2]; 1000 simulations were generated (RIF). Dose adjustments of DRV/RTV 1200/200 mg qd, 800/100 mg and 1200/150
mg twice daily (bid) were simulated to overcome the interaction. DRV trough (Ctrough) for each dosing scenario was
compared to the reference (-RIF) by GMR (90% CI).
Results: DRV and RTV were described by a 1 and 2compartment model, respectively. A maximum effect model,
with RTV inhibiting DRV CL/F, best described the relationship
between the drugs. Compared to the reference (-RIF),
simulated DRV Ctrough was 70%, 46% and 20% lower for
800/100 mg qd, 1200/200 mg qd and 800/100 mg bid all
RIF, respectively. Ctrough was 38% higher with 1200/150 mg
bid RIF (Table 1).
Conclusions: Modelling and simulation was used to investigate the theoretical impact of RIF on DRV/RTV PK. Based on
simulations, 800/100 mg and 1200/150 mg both bid could
largely overcome the impact of the interaction. However, the
risk of increased RTV-related side effects and higher pill
burden should be considered. In vitro work is ongoing to
develop a physiologically based model characterizing the
interaction and informing simulations.
References
1. Dickinson L, Jackson A, Garvey L, Watson V, Khoo S, Winston A,
et al. 11th International Congress on Drug Therapy in HIV, 1115
November 2012. Glasgow, UK. Poster P066;
2. Zhang C, Denti P, Decloedt E, et al. Model-based approach to
dose optimization of lopinavir/ritonavir when co-administered with
rifampicin. Br J Clin Pharmacol. 2011;73(5):75867.
P055
CSF LPV concentrations and viral load in viral suppressed
patients on LPV/r monotherapy given once daily
Juan Tiraboschi1; Arkaitz Imaz1; Elena Ferrer1; Maria Saumoy1;
Nerea Rozas2; Marga Maso2; Antonia Vila1; Jordi Niubo3 and
Daniel Podzamczer1
1
HIV Unit, Infectious Disease, Hospital Universitari de Bellvitge,
Barcelona, Spain. 2HIV Unit, Hospital Universitari de Bellvitge,
Barcelona, Spain. 3Microbiology Service, Hospital Universitari de
Bellvitge, Barcelona, Spain.
Introduction: Plasma trough concentrations of lopinavir (LPV)
given as LPV/r 800/200 mg once daily (OD) are reduced in
comparison with 400/100 mg twice daily (BID). While OD
dosage of LPV/r is sufficient to achieve viral suppression in
plasma, data about drug penetration and viral suppression
in central nervous system (CNS) is needed, mainly if LPVr
is used as maintenance monotherapy strategy in selected
patients. The objective of this study was to evaluate CSF HIV1 RNA and CSF LPV concentrations in patients receiving LPV/r
monotherapy OD (LPVrMOD).
Material and Methods: This is a cross-sectional sub-study
within a prospective, open-label pilot simplification study to
evaluate the efficacy and safety of LPV/rMOD in virologically
suppressed patients previously receiving a BID LPV/r monotherapy regimen (LPV/rMBID), the ‘‘Kmon study’’ (NCT
01581853). To assess LPV concentrations and HIV-1 RNA in
CSF, a lumbar puncture (LP) was performed in a subgroup of
patients after at least one month of LPVrMOD treatment.
Plasma-paired samples of all patients were also obtained.
HIV-1 RNA was determined by real-time PCR (limit of
detection 40 copies/mL). Liquid chromatography-tandem
Abstract P054Table 1. Summary of model simulated DRV Ctrough concentrations in the absence and presence of RIF and following
dose adjustment in combination with RIF. The changes in simulated DRV Ctrough are presented as GMR (90% CI)
Regimen
Geometric mean (90% CI)
GMR (90% CI)
800/100 mg qd -RIF (reference)
800/100 mg qd RIF
1.642 (15821.702)
0.486 (0.4610.511)
0.296 (0.2930.299)
0.538 (0.5330.542)
1200/200 mg qd RIF
0.883 (0.8390.927)
800/100 mg bid RIF
1.311 (1.2621.359)
0.798 (0.7610.837)
1200/150 mg bid RIF
2.270 (2.1912.349)
1.383 (1.3191.449)
67
mass spectrometry (Tandem labs, NJ) was used to determine
CSF and blood plasma LPV concentrations.
Results: Nine patients were included. Median (range) age
was 48 (3456) years, median CD4 cell count 672 (252
1,408) cells/mL, median nadir CD4 count 125 (35537)
cells/mL and 40% of subjects were HCV-positive. Before
starting LPV/rMOD median time on a LPV/r-containing regimen and on LPV/rMBID were 9 (411) years and 15 (724)
months respectively, median time with undetectable HIV viral
load was 5 (312) years and 2 patients had a previous
documented blip. LP was performed a median of 24 (836)
weeks after starting LPV/rMOD and 24 (1128) hours after
the last LPV/rMOD dose CSF and plasma HIV RNA was 40
copies/mL in all patients. Median LPV CSF concentration was
9.78 (1.9378.3) ng/mL, median LPV plasma concentration
1,103 (37716,700) ng/mL and median LPV CSF/plasma ratio
0.3% (0.11.2).
Conclusions: No CSF viral escape was detected and LPV
concentrations were above the IC50 for wtHIV-1 (1.9 ng/mL).
However, as concentrations were close to IC50 in some
patients, a careful clinical follow up of patients receiving this
regimen would be advisable. Larger longitudinal studies will
be helpful for a better understanding of the CNS antiviral
activity of LPVr monotherapy.
P057
Potential implications of CYP3A4, CYP3A5 and MDR-1
genetic variants on the efficacy of Lopinavir/Ritonavir
(LPV/r) monotherapy in HIV-1 patients
Giulia Berno1; Mauro Zaccarelli2; Caterina Gori1;
Massimo Tempestilli3; Luigia Pucci3; Andrea Antinori2; Carlo Federico
Perno4; Leopoldo Paolo Pucillo3 and Roberta D’Arrigo3
1
Antiviral Drug Monitoring Unit, National Institute for Infectious
Disease ‘‘L.Spallanzani’’, Rome, Italy. 2Clinical Department, National
Institute for Infectious Disease ‘‘L.Spallanzani’’, Rome, Italy. 3Clinical
Biochemistry and Pharmacology Laboratory, National Institute for
Infectious Disease ‘‘L.Spallanzani’’, Rome, Italy. 4Department of
Experimental Medicine and Surgery, University of Rome Tor Vergata,
Rome, Italy.
Poster Abstracts
Introduction: Several genetic single nucleotide polymorphisms
(SNPs) in biotransformation enzymes (CYP3A4, CYP3A5) or
transporter proteins (multidrug resistance MDR1 gene product, P-gp) are involved in PI metabolism so that PI pharmacokinetics is characterized by a large inter-individual variability.
The aim of this study was: (i) to develop an in-house PCR/direct
sequencing, based on DNA purification of full-length CYP3A4
and CYP3A5 genes (SNPs) and MDR1 C3435T variant; (ii) to
investigate association of CYP3A4 and CYP3A5 reported or
unreported genetic polymorphisms and MDR1-C3435T (CC
homozygote, CT heterozygote, TT homozygote) with clinical
outcome of HIV-1 infected subjects treated with PI.
Methods: Overall, 39 HIV-1 infected patients receiving
boosted Lopinavir (LPV/r) monotherapy after virological
suppression were genotyped and analyzed through PCR and
direct sequencing of full-length CYP3A4 and CYP3A5 gene
sequences[1] and MDR1 gene (C3435T). CD4T-cell counts
and plasma viral load were analyzed before and after LPV/r
initiation; LPV/r therapeutic drug monitoring (TDM) was
determined at 12-hours.
Results: LPV/r TDM (ng/ml) did not show significant differences among CYP3A4 or CYP3A5 SNPs, although a mean
lower level of LPV/r was associated with detection of several
SNPs: CYP3A5*3 rs776746; CYP3A5 rs28365088, CYP3A5
rs15524, CYP3A4 rs2687116, and a not already described
polymorphism CYP3A4 nt20338. In follow-up analysis, B90%
adherence was the main factor associated with virological
failure of LPV/r monotherapy (83.3% of failure vs 34.4%,
pB0.001 at log-rank test). Adjusting for adherence, the
detection of a single CYP3A5*3 rs776746 and CYP3A5
rs15524 SNPs was associated with higher probability of
LPV/r monotherapy failure (p B0.01), and in general, detection of any CYP3A5 SNP was associated with failure (26.2% vs
58.3%, p0.067). No-association with detection of any
CYP3A4 SNPs was found. MDR1 TT variants showed significant lower frequency of treatment failure (0.0% vs 47.7%,
p0.026), since non-TT homozygote patient failed LPV/r
monotherapy.
Conclusions: Efficacy of PI monotherapy is strongly dependent from patient adherence, but, in adherent patients,
genetic factors, such as CYP3A5 and MDR1-C3435T gene
Abstract P057Figure 1. a) Probability of failure of LPV/r monotherapy by treatment adherence; b) Probability of failure of LPV/r
monotherapy by MDR1 gene (C3435T).
68
variants, may affect the response to treatment, though
their role, as well of other genetic variants, need further
investigation.
Reference
1. Berno G, Zaccarelli M, Gori C, Tempestilli M, Antinori A, Perno CF,
et al. Analysis of single-nucleotide polymorphisms (SNPs) in human
CYP3A4 and CYP3A5 genes: potential implications for the metabolism of HIV drugs. BMC Med Genet. 2014;15:76.
Poster Abstracts
regardless of the type of tumour, and type and duration of
chemotherapy. Pharmacokinetic data show adequate raltegravir levels.
COMMUNITY INITIATIVES
P059
P058
Should we offer routine hepatitis C antibody testing in men
who have sex with men?
Efficacy, safety, and lack of interactions with the use of
raltegravir in HIV-infected patients undergoing
antineoplastic chemotherapy
Christopher Ward and Vincent Lee
Manchester Centre for Sexual Health, Central Manchester University
Hospitals NHS Foundation Trust, Manchester, UK.
Sara Bañón; Isabel Machuca; Susana Araujo; Ana Moreno; Marı́a
J. Perez-Elı́as; Santiago Moreno and Jose Luis Casado
Infectious Diseases, Ramon y Cajal Hospital, Madrid, Spain.
Introduction: Concomitant use of combination antiretroviral
regimen (cART) and cancer chemotherapy is difficult due to
complex interactions and increased toxicity. Raltegravir could
be an adequate option through its favourable drug-drug
interaction profile.
Methods: Prospective longitudinal study of HIV patients with
cancer, AIDS related or not, undergoing chemotherapy.
Patients without resistance or previous failure were switched
or initiated raltegravir plus two nucleoside analogues. Plasma
trough levels of raltegravir were measured.
Results: Overall, 28 patients receiving a raltegravir-based
regimen (4 naive) with tenofovir-emtricitabine (18 cases) or
abacavir-lamivudine (10 cases) were included. Mean age was
46.2 years (IQR, 3952.7), and 79% were male. Median time
of HIV was 201.7 months, CD4 nadir was 268 cells/mm3,
and 75% had previous AIDS. At the diagnosis of neoplasia,
17 were on protease inhibitors and 4 with efavirenz. Ten
patients had a non-HIV-related cancer (three breast, two
pancreatic, one Ewing sarcoma, one myeloblastic leukemia,
one melanoma, one parotid adenocarcinoma, one lung), and
18 had an HIV-related cancer (nine non-Hodgkin lymphoma,
seven Hodgkin disease, two anal). Overall, 43% of patients
received more than one line of chemotherapy, including
antimetabolites in 12 patients (5-FU, capecitabine, methotrexate, gemcitabine), alkylating agents in 12 cases (ciclophosphamide, iphosphamide), vinca alkaloids in 20 patients
(vincristine, vinblastine, vindesine), antitumor antibiotics in
16 cases (adriamycin), cisplatin o carboplatin in six and
monoclonal antibodies in six patients (rituximab, trastuzumab, cetuximab). Six patients modified the doses of
antineoplastic agents due to toxicity (four neutropenia), not
related to raltegravir. During a median follow up of 12.7
patients-year in concomitant therapy, there was only 1 case
of virological failure and no patient discontinued raltegravir.
Plasma concentrations of raltegravir in eight patients showed
a median concentration of 143 ng/mL (79455). Four
patients (14%) died during the study, not related to AIDS
progression. Raltegravir was continued after chemotherapy
in all the cases.
Conclusions: A raltegravir-based therapy is safe and effective
in HIV patients undergoing antineoplastic chemotherapy,
Introduction: There has been a significant rise in the
number of HIV positive men who have sex with men
(MSM) co-infected with hepatitis C (HCV). Most infections
are thought to occur through high risk sexual practices,
exacerbated by drug use. Previous data has suggested
no need for routine screening in HIV negative MSM. We
looked at HCV antibody testing and HCV risk assessment in all
MSM clinic attenders as part of a Public Health England
initiative.
Materials and Methods: Routine HCV antibody testing was
offered to all MSM attending a large inner city sexual health
clinic from April to June 2014. Patients were asked to fill in a
questionnaire assessing HCV risk. Demographic data, HIV
status and STI results were collected and compared.
Results: We collected 471 HCV risk assessment questionnaires
during the eight-week period. The median age was 34 (range
1871) and 403 (85.6%) were White British. Ten (2.1%)
patients were known to be HCV positive, of which 3 were
on treatment and 5 (1.1%) had cleared HCV. One hundred and
forty-nine (31.6%) patients were HIV negative, 254 (53.9%)
were HIV positive and 68 (14.5%) had unknown HIV status at
time of clinic visit. In the last three months 151 (32.1%)
reported unprotected receptive anal intercourse, 58 (12.3%)
reported group sex, 11 (2.3%) reported receptive fisting and
32 (6.8%) reported more than 10 partners. Eighty-seven
(18.5%) patients had shared notes/straws to snort drugs and
29 (6.2%) reported injecting drugs or slamming. One hundred
and forty-two (30.0%) patients reported recreational drug use
in the last 12 months, with cocaine, methadrone and ketamine
most popular. One hundred and fifteen (24.4%) patients
reported sex under the influence of recreational drugs. There
were no statistical differences between HIV positive and HIV
negative patients in their risk, sexual behaviour and drug use.
STI screens were performed on 269 patients with nine (3.3%)
new HIV diagnoses, four (1.5%) early syphilis, and 28 (10.4%)
rectal gonorrhoea infections. There were three (1.1%) new
HCV diagnoses, and one (33.3%) was in an HIV negative
patient.
Conclusions: Our results show increased risk behaviour for
both HIV positive and HIV negative MSM. There are a high
number of patients using party drugs, participating in group
sex and not using condoms, leading to high rates of new
STI diagnoses. With similar rates of risk we believe HCV testing
69
and risk assessment should be considered in all MSM regardless of HIV status.
P060
HIV positive asylum seekers receiving the order to leave the
Belgian territory
Remy Demeester and Jean-Claude Legrand
Infectious Diseases, University Hospital of Charleroi, Charleroi,
Belgium.
Introduction: In a human rights based approach, the Parliamentary Assembly of the Council of Europe has recently
released a resolution about migrants and refugees and the
fight against HIV [1]. It states that ‘‘an HIV positive migrant
should never be expelled when it is clear that he will not
receive adequate health care and assistance in the country to
which he is being sent back. To do otherwise would amount to
a death sentence for that person.’’ Nevertheless, in Belgium,
for the last 2 years, none of the HIV-infected migrants in care
in the AIDS Reference Centers (ARC) received the right to stay
in Belgium for medical reasons.
Methods: We identified all HIV-infected asylum seekers in
care between 1 July 2012 and 1 July 2014 in the ARC of
Charleroi, Belgium, and we analyzed their medical and social
files.
Results: Among the 302 patients in active follow up in our
ARC, 45 HIV positive asylum seekers were in care during the
last 2 years. Male/female ratio was 0/96. Mean age was 35
years. Countries of origin and reasons for migration are
detailed in the Table. 18% (8/45) knew their seropositivity
before arriving in Europe. All the patients introduced an
asylum request, 29 (64%) have received a negative answer
and an order to leave the territory, 4 (9%) were regularized
for non-medical reasons (see Table), 4 (9%) are waiting for an
answer and for 8 (18%) outcome is unknown due to lost
follow up (LFU). 31 (69%) patients have also introduced a
request to stay for medical reasons: 18 (58%) have received a
refusal, 7 (23%) are still waiting for an answer, and 6 (19%)
are LFU. Only 23 (51%) patients are still in care in our ARC on
1 July 2014 (see Table). The immigration office bases its
decisions on availability of the treatment in the country even
if accessible only to a limited number of patients.
Poster Abstracts
Conclusions: Decisions taken by the Belgian authorities for the
last two years concerning HIV-infected asylum seekers do not
guarantee the continuity of care of those patients and push
them towards illegality. Such decisions ignore the international commitments of Belgium in the fight against HIV[2] and
are contradictory with the recommendations of the recent
resolution of the Council of Europe[1]. An approach more
respectful of Human Rights in the decisions concerning the
seropositive asylum seekers patients taken by the authorities
is urgently needed in Belgium. We invite our European
colleagues to describe the situation of the HIV asylum seekers
in their countries.
References
1. Council of Europe: Parliamentary Assembly: Resolution 1997
(2014). Migrants and refugees and the fight against AIDS. Available
from: http://hub.coe.int/en/
2. Policy paper: the Belgian contribution to the fight against HIV/
AIDS worldwide. Federal Public Service Foreign Affairs, Foreign Trade
and Development Cooperation. March 2006. Available from: www.
diplomatie.be
P061
EATG training academy STEP-UP: skills training to empower
patients
Oleksandr Martynenko1; Damian Kelly2 and Vanessa Say3
1
Training and Capacity Building, The European AIDS Treatment
Group, Brussels, Belgium. 2Training and Capacity Building, The
European AIDS Treatment Group, Manchester, UK. 3Communications,
Packer Forbes, London, UK.
Introduction: Most existing conventional capacity building
and educational programs are currently executed on ad-hoc
basis. Such approach no longer responds to the needs and
capabilities of patients, supporters and healthcare providers
in their engagement with and contribution to response to
HIV/AIDS. In contrast, long-term, course-like trainings have
considerably broader thematic scope and are conducive to
more effective and sustainable learning, exchange of experience and best practices.
Method: Over the period of one year, the Academy trains a
cohort of 20 activists (10 from East Europe and Central Asia
and 10 from Western and Southern Europe). The Academy
goes beyond ‘‘treatment only’’ paradigm. Conceptually, five
Abstract P060Table 1. Characteristics and detailed situations of the HIV positive asylum seekers in the ARC of Charleroi
Country of origin (N 45) (n)
Rwanda (7), Democratic Republic of Congo (6), other country of sub-
Reported reason for migration of the patients ignoring their HIV
Political (18 (47%)), personal threats (5 (11%)), health (1 (11%)),
Saharan Africa (23), Maghreb (2), ex USSR (5), other (2)
seropositivity or positive status (N 37); (n (%))
Reported reason for migration among patients knowing their HIV
positive status (N 8); (n)
economical (3 (7%)), familial (1 (4%)), unknown (9 (20%))
Health (4 (multiR virus (2), treatment unaffordable (1), hemodialysis
needed (1)) political threat (3), family reunification (1)
Reason for regularization (N 4); (n)
Political reason (2), family reunification (1), humanitarian reason (1).
Retention in care (N 45) (n (%))
No regularization through the medical procedure
LFU (12 (27%)), followed in another ARC (8 (18%)), back to their home
country (2 (4%)), follow up in our ARC (23 (51%))
70
training modules are grouped under three larger domains:
treatment literacy, treatment advocacy and treatment activism, thus covering most of the topics pertinent to the current
discourse of HIV and related co-infections. To ensure cascade
effect and sustainability of the learning, the trainees are
offered participation in pan-European HIV conferences (EACS
and HIV Glasgow) and resources for follow-up activities.
Results: The trainees empirically applied the knowledge to the
benefits of their communities. In Uzbekistan, a trainee introduced EACS treatment guidelines to fellow medical students
and junior doctors. In Armenia and Albania a series of smallscale trainings were held, outreaching to young homeless
people who were traditionally excluded from HIV treatment
and prevention discourse in the two countries. A trainee from
Spain used the materials of the Academy in his work in
Mozambique and the Spanish Ministry of Health. Five trainees
engaged in a joint European cross-countries project on treatment literacy for young people who are most at risk of
infection.
Conclusions: EATG Training Academy is a unique initiative in
the WHO Europe region that both trains future treatment
activists and addresses treatment literacy, advocacy and
advocacy topics. This type of capacity building can respond
to existing HIV-related problems more effectively using less
limited resources and reaching out to larger communities.
P062
Using social network methods to reach out-of-care or ARTnonadherent HIV injection drug users in Russia:
addressing a gap in the treatment cascade
Yuri Amirkhanian1; Jeffrey Kelly1; Anna Kuznetsova2;
Anastasia Meylakhs2; Alexey Yakovlev2; Vladimir Musatov2 and
Nikolay Chaika3
1
Medical College of Wisconsin, Center for AIDS Intervention
Research (CAIR), Milwaukee, WI, USA. 2Botkin Hospital for Infectious
Diseases, Interdisciplinary Center for AIDS Research (ICART), St.
Petersburg, Russian Federation. 3Information, St. Petersburg Pasteur
Institute, St. Petersburg, Russian Federation.
Introduction: HIV treatment to reduce downstream HIV
incidence and to decrease disease mortality and morbidity
at a population level both require that hidden, out-of-care
people living with HIV (PLH) in the community be reached and
engaged to enter care. This research evaluated the feasibility
of reaching out-of-care or non-adherent PLH through members of their social networks in St Petersburg, Russia.
Materials and Methods: To recruit a social network sample of
HIV-positive injection drug users, 16 HIV seeds were
enrolled into the study through PLH-oriented websites and
online forums using recruitment ads or approached in needle
exchange sites. Interested persons called the study phone
number and completed a brief eligibility interview. Seed
inclusion criteria were HIV status, being 18 years or older,
having ever injected drugs, and having not visited an HIV
doctor in the past 6 months. Seeds provided blood specimens
tested for HIV to confirm their self-reported status. Eligible
seeds were enrolled, completed brief network elicitation
interview, and were asked to invite their own HIV friends
into the study. Incentives were provided as compensation for
Poster Abstracts
participants’ time and additional smaller incentives were
provided for inviting each HIV network member to also
participate. The seed’s PLH friends established the first ring
of participants who, in turn were asked to invite their own
PLH friends (second ring). All study participants completed
assessment of psychosocial wellbeing and sexual and injection-related HIV risk behaviour. Blood samples were collected
from all participants to confirm their HIV status.
Results: Through this chain referral process, the initial 16 seeds
led to the enrolment of a total of 66 PLH from the community
(mean 4 per initial seed), most of whom like the seed were not presently in HIV care or were ART non-adherent.
Conclusions: Implementation of treatment cascade goals
requires complementing conventional paths of identifying
PLH with feasible and effective community-based approaches
such as described in this study. This research establishes that
PLH are connected in their day-to-day social networks with
other HIV persons and shows that social network methods
can be employed to reach infected persons through their
connections with other PLH. This method has the potential to
expand the reach of medical care efforts and ART uptake.
P063
Transmission route and reasons for HIV testing among
recently diagnosed HIV patients in HIV-TR cohort,
20112012
Basak Dokuzoguz1; Volkan Korten2; Deniz Gökengin3;
Muzaffer Fincanci4; Taner Yildirmak5; Uzun Nuray Kes6;
Nuriye Tasdelen Fisgin7; Dilara Inan8; Haluk Eraksoy9 and
Halis Akalin10
1
Infectious Diseases and Clinical Microbiology, Ankara Numune
Education Training and Research Hospital, Ankara, Turkey. 2Infectious
Diseases, Marmara University Hospital, Istanbul, Turkey. 3Infectious
Diseases, Ege University Hospital, Izmir, Turkey. 4Infectious Diseases,
Istanbul Education and Research Hospital, Istanbul, Turkey.
5
Infectious Diseases, Okmeydaný Education and Research Hospital,
Istanbul, Turkey. 6Infectious Diseases, Þiþli Education and Research
Hospital, Istanbul, Turkey. 7Infectious Diseases, 19 Mayýs University
Hospital, Samsun, Turkey. 8Infectious Diseases, Akdeniz University
Hospital, Antalya, Turkey. 9Infectious Diseases, Istanbul Medical
School, Istanbul University, Istanbul, Turkey. 10Infectious Diseases,
Uludað University Hospital, Bursa, Turkey.
Introduction: Routes of transmission and reasons for HIV
testing are important epidemiologic data to analyze the
epidemic and to tailor the response to AIDS. The aim of this
study was to analyze reasons for testing and transmission
ways of HIV among recently diagnosed HIV patients registered in the multicenter HIV-TR cohort in Turkey.
Methods: Transmission ways and reasons for testing of all
patients diagnosed in 2011 and 2012 were recorded on a
web-based data collection system and were analyzed retrospectively.
Results: The study included 693 patients (561 male, 132
female) from 24 sites. Reason for HIV testing was available in
640 patients (92%). The most common reason for HIV testing
was diagnostic workout for other conditions or illness followed
by patient-initiated testing. The reasons for testing were listed
in Table 1. The most common routes of HIV transmission were
heterosexual intercourse (62.7%) and sex among men who
71
Poster Abstracts
Reasons for HIV testing
Reason for testing
N
%
Blood/organ donation
63
9.8
Prior to surgical/parenteral intervention
63
9.8
Premarital testing
20
3.1
Screening for pregnancy
11
1.7
Patient-initiated
98
15.3
Diagnostic workout for other medical condition/illness 312
48.8
Job application
Other
1.3
10.2
Total
8
65
640 100
have sex with men (MSM) (22.6%). At the time of HIV diagnosis,
the mean CD4 lymphocyte cell count was 355/mm3 (31433/
mm3). Primary HIV infection was determined in 42/693 (6%)
patients and 9/693 (% 1, 2) cases were considered ‘‘probable
primary HIV infection.’’ The majority of the cases presented to
a clinic for follow-up right after the diagnosis. On the other
hand 32/616 (5.2%) patients delayed their presentation for
more than 3 months. The longest delay was 11 months.
Conclusions: The results of the database suggest that targeted
testing is lacking in the country. The shift toward homosexual
transmission during the last 2 years emphasizes the need for
targeted interventions. Patients present relatively late and
HIV infection could only be diagnosed when immunosuppression related findings appeared. Patient-initiated testing,an
indicator of awareness, was very low suggesting a need to
scale-up awareness raising interventions.
P065
HIV infection early diagnosis experience in primary care
Francisco Jover Diaz1; Paz Ortega2; Pedro Antequera3; Blas Cloquell4;
Marta Alcaraz5; Mavi Hernandis4; Carlos Nuñez5; Rosario Lloret4;
Faustino Perez5; Sabina Jover Perez5; Fernando Buñuel3;
Francisco Gomez2; Marta Sanz5; Rafael Ordovas5;
Francisco Torregrosa4; Ángela Barceló4; Consuelo Masegosa6;
Victoria Ortiz de la Tabla3 and Jose Marı́a Cuadrado1
1
Infectious Diseases, Hospital Clinico San Juan Alicante, Alicante,
Spain. 2Hospital Clinico San Juan Alicante, CSI C/Gerona, Alicante,
Spain. 3Microbiology, Hospital Clinico San Juan Alicante, Alicante,
Spain. 4Hospital Clinico San Juan Alicante, CS El Cabo, Alicante, Spain.
5
Hospital Clinico San Juan Alicante, CS Sta Faz, Alicante, Spain.
6
Hospital Clinico San Juan Alicante, CS Juan XXIII, Alicante, Spain.
Introduction: Traditional screening system focus on classic
risk factors ‘‘lost’’ a substantial proportion of HIV-infected
patients. Several organizations such as CDC or USPS Task
Force favour universal screening for HIV infection for good
cost-effectiveness profile. In a previous study prevalence of
HIV infection in patients attending our infectious diseases
department was high (5.4%).
Objective: To determine prevalence of HIV infection in
patients aged 2055 years in primary care (PC).
Material and Methods: A propsective observational study
was undertaken between February and June 2013. We
performed a screening of HIV infection type ‘‘Opt-out’’
(offering voluntary rejection) in 4 PC centers (32 Physicians)
in San Juan-Alicante. Sample size (n 318) for a prevalence of
1% and a confidence level of 97% was calculated. Nevertheless, other PC physician not recruiting patients performed
HIV testing according clinical risk factors.
Results: HIV testing was offered to 508 patients. Mean age
38.9910 years (58.5% female). Overall, 430 (83.8%) agreed to
participate. Finally, 368 patients (71.7% of total) were tested
for HIV. No patient had a positive result (100% ELISA HIV
negative). However, following clinical practice, 3 patients
were diagnosed of HIV in the same period by non-recruiting
physicians. In 2 cases, serology was performed at the patient’s
request and in one case by constitutional syndrome. The 3
patients were MSM.
Conclusions: 1) In our study, we detected no new cases of
HIV infection through universal screening. 2) Our screened
population could be lower-risk because of high percentage of
women included (58.5%). 3) Performing HIV opt-in screening
(clinical practice), we detected 3 cases in the same period,
all having HIV risk factors (MSM). 4) These results suggest
that opt-out screening should be developed in high-risk
populations. It is still to be determined what is the best
screening strategy in low-risk populations such as ours.
P066
HIV test: which is your best? A National survey on testing
preferences among MSM in Italy
Sandro Mattioli1; Giulio Maria Corbelli2; Stefano Pieralli1 and
Michele Degli Esposti1
1
Plus onlus, na, Bologna, Italy. 2European AIDS Treatment Group, na,
Bruxelles, Belgium.
Introduction: HIV testing opportunities in Italy are frequently
limited to the hospital setting. Experiences in other countries
show that offering HIV testing in other facilities could
improve HIV testing uptake.
Methods: An internet-based survey was conducted between
March 10 and April 3, 2014.
Results: A total number of 348 questionnaires were collected.
Responders were 88% male. Most represented age groups
were 2534 (35%) and 3544 (25%). Most of the responders
identify themselves as homosexual (81%) or bisexual (9%).
Half of responders had an HIV test within 2 years (56%) while
18% never tested for HIV. Among all responders, 61% had
more than 2 sexual partners in the past year. Reported
condom use in the past year was: always 39%, always but
once 11%, sometimes 27%, never 14%. Most known places to
have an HIV test is the hospital (95%), STI clinic (58%) and
chemical analysis laboratory (54%); most used places are
hospital (73%), STI clinic (30%), laboratory (22%) while 5
responders reported having had a self-test at home. Preferred
places where to have an HIV test is self-testing at home (53%),
hospital (36%), pharmacy (32%) and headquarter of an
organization (31%). Most known testing method is draw
blood from vein (97%), which is also most used (80%) but the
least preferred (31%) while saliva (65%) and finger prick (56%)
are the preferred choices. Most responders know that
physicians (84%) and nurses (77%) are those who perform
72
Which
places for
HIV testing
do you
know?
%
N
Hospital
94.8
330
STI clinic
57.8
201
Drug abuse
service
23.6
82
2.6
9
Analysis
Lab
53.7
187
Street unit
25.9
Org.
Headquarter
Home
testing
Pharmacy
Don’t
know
Survey results
Which places
for HIV
testing did
you use?
Which places
for HIV
testing
would you
like to use?
%
N
Hospital
73.0
254
STI clinic
30.5
106
Drug abuse
service
2.3
8
Drug abuse
service
Pharmacy
0.3
1
Analysis Lab
21.6
90
Street unit
23.6
82
8.6
0.9
%
N
Hospital
36.5
127
STI clinic
27.3
Which
procedures
for HIV
testing do
you know?
%
N
Which
procedures
for HIV
testing did
you use?
96.6
336
95
Vein blood
draw
Finger prick
30.5
106
Vein blood
draw
Finger prick
4.6
16
Saliva
43.1
150
Saliva
Pharmacy
31.9
111
0.6
2
Never
tested
75
Analysis Lab
20.7
72
3.2
11
Street unit
22.4
78
Org. Headquarter
6.9
24
Org.
Headquarter
31.0
108
30
Home testing
1.4
5
Home testing
52.6
183
3
Never tested
16.1
56
10.6
37
Don’t know
0.6
2
HIV, will
not test
Don’t know
1.1
4
Don’t know
Don’t know
%
N
80.5
280
5.5
Which
procedures
for HIV
testing
would you
like to use?
%
N
Which
operator for
HIV testing
do you
know?
%
N
Which
operator for
HIV testing
did you use?
%
N
Which
operator for
HIV testing
would you
like to use?
%
N
31.3
109
Physician
83.9
292
Physician
60.1
209
Physician
54.0
188
19
Vein blood
draw
Finger prick
55.7
194
Nurse
76.7
267
Nurse
64.9
226
Nurse
45.7
159
10.6
37
Saliva
65.2
227
Pharmacist
2.6
9
0.3
1
Pharmacist
20.7
72
16.7
58
HIV, will
not test
16.1
56
Lab operator
39.9
139
19.3
67
Lab operator
27.6
96
0.3
1
Don’t know
0.6
2
Volunteer
23.9
83
Volunteer
9.8
34
Volunteer
38.5
134
Myself
(hometesting)
Don’t know
14.4
50
2.3
8
160
4
16.4
57
Myself
(hometesting)
HIV, will
not test
46.0
1.1
Myself
(hometesting)
Never tested
14.9
52
Don’t know
0.3
1
1.4
5
Pharmacist
Lab operator
Don’t know
How would your
preferred test be?
It’s mandatory to
be free
I can pay 510 t
to have it as I want
it
Medical
prescription must
not be necessary
Result must be
available rapidly
(2030 minutes)
It’s mandatory to
be extremely
reliable
Name, surname,
ID must not be
requested
I want a physician
to be present
Don’t want to
receive
counselling
I want to receive
peer-counselling
I want to receive
counselling from a
physician
Other
%
N
63.2
220
39.4
137
74.7
260
55.7
194
85.9
299
44.5
155
21.0
73
29.0
101
35.6
124
23.9
83
0.9
3
Poster Abstracts
73
HIV tests and most of them had an HIV test with them (60%
and 65% respectively). Physicians are the preferred operators
(54%) followed by self-testing (46%), nurses (46%) and peervolunteers (39%). The ideal HIV test should be: reliable (86%),
with no medical prescription (75%), free (63%), rapid (55%),
with no personal information collected (45%), with the
opportunity to speak with a peer-counsellor (36%).
Conclusions: Changing HIV testing policies in Italy is urgently
needed in order to grant a better access to the service: waiting
for the results and bureaucratic obligations represent the
major barriers to be removed. Home-testing and communitybased testing seem to be among the best ways to offer new
opportunities though they may require a change in the legal,
social and cultural context to be implemented and home
testing will not allow any kind of support for newly diagnosed
people.
P067
Health literacy, source of information and impact on
adherence to therapy in people living with HIV
Thomas Ernst Dorner1; Kathrin Schulte-Hermann2; Matteo Zanini3;
Birgit Leichsenring4 and Wiltrut Stefanek5
1
Institute of Social Medicine, Centre for Public Health, University of
Vienna, Vienna, Austria. 2Medical Department, MSD Austria, Vienna,
Austria. 3Specialty, MSD Austria, Vienna, Austria. 4Medical
Information/Dokumentation, AIDS Hilfe Wien, Vienna, Austria.
5
PULSHIV, Patient Organisation, Vienna, Austria.
Introduction: Adequate information and health literacy (HL)
has a high impact on patients understanding on the causes
and consequences of many chronic diseases, including HIV,
and is a crucial prerequisite to ensure adherence to therapy
regimens. Several Austrian patient organizations developed
an online survey together with MSD (the so-called ‘‘PABtest’’) aimed to evaluate how people living with HIV perceive
the level of care in Austria.
Materials and Methods: An online survey has been developed to assess HL in people living with HIV and to evaluate
the impact of HL on therapy adherence. HL was assessed
with seven items regarding the self-rated comprehension of
HIV related information, which showed a high reliability
(Cronbach’s alpha 0.876). A low health literacy was defined
by reaching a score below the median of 20 points in the
related indicator.
Results: A total of 303 subjects completed the questionnaire.
Women slightly had more often a low HL than men (57.1% vs
44.7%, p 0.335). Heterosexual subjects had more often a
low HL compared to homosexual ones (58.3% vs 38.1%,
p0.007). Health literacy slightly increased with age (not
significant). An increasing education level correlated with
higher HL, (66.7%, 46.2%, and 38.9% of persons showed low
HL with primary, secondary and tertiary education, respectively, p 0.037). The number of missed appointments with
the HIV physician was significantly higher in the low HL
population (30.0% vs 14.4%, p0.002), which also showed
to be more prone to interrupt the therapy without consulting
a physician (22.4% vs 9.8%, p0.006). The low HL population, however, did not report of having forgotten the
medication intake more often than the one with high HL
Poster Abstracts
Abstract P067Figure 1. Sources of information in HIV patients
with high and low health literacy (absolute numbers).
(33.1% vs 39.1%, p 0.305). The most important source of
information is the treating physician, followed by NGOs/
patient organizations and the internet (Figure 1).
Conclusions: There are significant differences in HL between
different sub-groups in the HIV community. Low HL is
significantly associated with a higher frequency of missed
doctor appointments and interruptions of treatment, but
does not impact adherence to therapy (self-reported). The
identified information providers (medical doctors, NGOs/
patient organizations) should be encouraged to contribute
towards increased HL in HIV patients.
P068
Involvement of HIV patients in treatment-related decisions
Matteo Zanini1; Kathrin Schulte-Hermann2; Birgit Leichsenring3;
Wiltrut Stefanek4 and Thomas Ernst Dorner5
1
Specialty, MSD Austria, Vienna, Austria. 2Medical Department, MSD
Austria, Vienna, Austria. 3Medical Information/Dokumentation, AIDS
Hilfe Wien, Vienna, Austria. 4PULSHIV, Patient Organisation, Vienna,
Austria. 5Institute of Social Medicine, Centre for Public Health,
Medical University of Vienna, Vienna, Austria.
Introduction: The improvement of antiretroviral therapy in
the past decades has had a major impact on life expectancy
and quality of life of people living with HIV, and also on the
relationship between patients and their physicians. What
used to be an acute treatment for life threatening complications, and an end-of-life therapy in the beginning of the
epidemic, turned over the time into a lifelong care. The good
relationship between patients and physicians represents the
cornerstone of an optimal long-term therapy. Shared decision
making between patients and physicians is a crucial prerequisite for the success of this approach. Several Austrian
patient organizations developed an online survey together
with MSD (the so-called ‘‘PAB-test’’) aimed to evaluate how
people living with HIV perceive the level of care in Austria.
Materials and Methods: An online survey has been developed to evaluate how people living with HIV feel about the
relationship with their physicians and to what extent they
feel involved in treatment related decisions.
Results: A total of 303 subjects completed the questionnaire.
44% felt ‘‘totally’’ involved in their therapy, 40% ‘‘strongly
74
Poster Abstracts
Abstract P068Figure 1. Importance of therapy-related factors for choice of ART.
involved’’, 12% ‘‘fairly involved’’, 3% ‘‘poorly involved’’ and
1% ‘‘not at all involved’’ in their therapy. The proportion of
subjects who felt totally involved in the therapy was equally
distributed between sex, sexual orientation, age groups,
groups of various education level, and between patients
treated predominantly in intramural or extramural medical
care. The most important factor for people living with HIV to
feel involved in their therapy is a low amount of long-term
ART-related side-effects (Figure 1).
Conclusions: The results show that the majority of people
living with HIV in Austria feel involved in therapy related
decisions. This proportion is equally distributed in patients
with different socio-demographic or socio-economic characteristics or level of medical care delivery. According to the
survey, the most important reason for people living with HIV to
be involved in their therapy is to avoid long-term side effects.
P069
Improve screening of HCV infection by targeting high
prevalence aged groups: analysis of a cohort of HCV and HIV
co-infected patients
Pedro Brogueira1; Ana Costa2; Ana Miranda1; Susana Peres1;
Teresa Baptista1; Isabel Aldir1; Isabel Antunes1; Fernando Ventura1;
Fernando Borges1 and Kamal Mansinho1
1
Infectious Diseases, Hospital de Egas Moniz, Lisboa, Portugal.
2
Family Medicine, USF Alpha Mouro, Sintra, Portugal.
Introduction: Hepatitis C constitutes a major public health
burden. In Portugal, the prevalence is estimated at 11.5%
[1]. Of these, only 30% are presumed to be diagnosed, which
reveals that most infections go unknown. The objective of
this study is to identify the age-range distribution at HCV
diagnosis and to identify the high-prevalence birth groups
that could be targeted for screening, as a strategy to increase
diagnosis and identify patients who would benefit most from
treatment.
Methods: Retrospective observational study of a cohort of
chronic HCV-infected and HIV co-infected patients followed
at an Infectious Diseases Center, diagnosed between 1979
and 2014 (Figure 1). Hepatic fibrosis evaluation was performed by real time elastography using METAVIR score.
Epidemiological, demographic, clinical, virological and therapeutic data was retrieved from clinical registries. Statistical
analysis was performed using Microsoft Excel 2010† . Chi2,
Student T were used for a significant p value of B0.05.
Results: Our study assessed a cohort of 665 patients: 442
(66.5%) HCV/HIV co-infected and 223 (33.5%) HCV monoinfected. There was a male predominance in both groups
(74.9% vs 70.9%). The mean age was 47 HCV/HIV vs 49 years;
Portuguese origin in 80% vs 83% and African in 14% vs 12%.
The most frequently assumed transmission route was by
intravenous drug use (IVDU) (81% vs 72%), followed by sexual
contact (18% vs 20%). Mean age at diagnosis was 32 vs
40 years. Mean time since HCV diagnosis was 14, 6 vs 9, 6 years.
Fibrosis stage evaluation by real time elastography was
available for 133 (30%) and 99 (44.4%) patients (HCV/HIV vs
HCV): 16% vs 13% F1; 32% vs 33% F2; 31% vs 35% F3; 21%
vs 18% F4. The peak prevalence occurred between the
birth intervals of 19601969 and 19701979 for both
groups, corresponding to 81% vs 66,8% (p 0.003) (Figure
1). About three quarters of all patients (76%) were born
between the year of 1960 and 1979, with a prevalence of
70% of IVDU.
75
Poster Abstracts
Abstract P069Figure 1. Distribution of HIV/HCV and HCV infected patients by date of birth (n=665).
Conclusions: In our cohort we identify a high risk population
for chronically HCV infection, which comprises people born
between 1960 and 1979, findings common to those with
mono or HIV co-infection. This finding is concordant with the
epidemic of IVDU in Portugal around 19801990. These
patients should be screened for diagnosis in order to be
treated and to prevent further disease progression.
Reference
1. Anjo J, Café A, Carvalho A, Doroana M, Fraga J, Gı́ria J, et al.
O Impacto da hepatite C em Portugal. GE J Port Gastrenterol.
2014;21(2):4454.
P070
Future prospectives of sub-Saharan women living with HIV
residing in France for more than seven years: prospective
pilot study
Svetlane Dimi1; Dominique Albucher2 and David Zucman1
1
Internal Medicine, Hopital Foch, Suresnes, France. 2Service Social,
Hopital Foch, Suresnes, France.
Introduction: In 2011, a French national survey of people living
with HIV (PLHIV) has shown that 40% of persons diagnosed
since 2003 are originated from sub-Saharan Africa, two thirds
of them being women. For them, in the short term, access to
social rights is a priority. Today, over 90% of PLHIV are treated
effectively and with the aging of this population, questions
about their future perspectives arise. Our service provides a
multidisciplinary (medical, psychological, social) approach to
PLHIV. The aim of our study is to describe the future perspectives of sub-Saharan women living with HIV residing in
France for more than 7 years, because it is the time required for
the implementation of fundamental rights and social insertion.
Do they plan to return to their country of origin after their
retirement? Does the HIV infection force them to stay in France?
Material and Methods: Prospective pilot mono-centric study.
Between January and April 2014, every HIV-infected woman
born in a sub-Saharan country, resident in France for at least
7 years, attending for their routine outpatient visit was
consecutively included. Data were collected through a
structured, semi-directed interview made by their usual
hospital physician or social worker.
Results: Consecutively, 76 women agreed to participate to
the interview, none refused. Mean age: 42 years [2670],
time since HIV diagnosis: 12 years [125]. HIV diagnosis
was made before arriving in France for 3% of them; in 33%
diagnosis was made in the year of arrival; diagnosis made
several years after arrival in 63%. Even if 69% of these women
had been irregularly residing in France for a period, all of
them had obtained a regular situation for residence and 50%
acquired the French nationality. Mean duration of residence
was 15 years [733]. Two thirds of them are employed. In the
future, although 50% plan to have a shared residence between
France and Africa, only 20% of them plan to settle back
definitely in Africa and no woman declared that she would
look for a medical follow up in Africa for their HIV infection.
Conclusions: This study shows a good integration in France
of HIV-infected sub-Saharan woman. Their links with Africa
remain strong but very few plan to return in their country
of origin due to lack of confidence in the African health
infrastructures.
COST EFFECTIVENESS
P071
Cost/efficacy analysis of preferred Spanish AIDS study group
regimens and the dual therapy with LPV/r3TC for initial
ART in HIV infected adults
Josép M Gatell1; José R Arribas2; Pablo Lázaro3 and
Antonio J Blasco3
1
Head Infectious Diseases and AIDS Units, Hospital Clinic-IDIBAPS,
Barcelona, Spain. 2HIV Unit, La Paz Hospital. IdiPAZ, Madrid, Spain.
3
Research, Advanced Techniques in Health Services Research (TAISS),
Madrid, Spain.
76
Poster Abstracts
Introduction: The National AIDS Plan and the Spanish AIDS
study group (GESIDA) panel of experts propose ‘‘preferred
regimens’’ of antiretroviral treatment (ART) as initial therapy
in HIV-infected patients for 2013 [1]. All these regimens are
triple therapy regimens. The Gardel Study assessed the
efficacy and safety of a dual therapy (DT) combination of
lopinavir/ritonavir (LPV/r) 400/100 mg BID lamivudine
(3TC) 150 mg BID [2]. The objective of this study is to
evaluate the costs and efficiency of initiating treatment with
the GESIDA ‘‘preferred regimens’’ and DT.
Materials and Methods: Economic assessment of costs and
efficiency (cost/efficacy) through decision tree analysis
models. Efficacy was defined as the probability of having
viral load B50 copies/mL at week 48, in an intention-totreat analysis. Cost of initiating treatment with an ART regime
was defined as the costs of ART and its consequences
(adverse effects, changes of ART regime and drug resistance
tests) during the first 48 weeks. The payer perspective
(Spanish National Health System) was applied considering
only differential direct costs: ART (official prizes), management of adverse effects, resistance tests, and determination
of HLA B*5701. The setting is Spain and the costs are those of
2013. A sensitivity deterministic analysis was conducted,
building three scenarios for each regime: base, most favourable and most unfavourable cases.
Results: In the base case scenario, the cost of initiating
treatment ranges from 5138 euros for DT, to 12,059 euros for
tenofovir DF/emtricitabine (TDF/FTC)raltegravir (RAL). The
efficacy ranges between 0.66 for abacavir (ABC)/3TCLPV/r
and ABC/3TCatazanavir (ATV)/r, and 0.88 for DT. Efficiency,
in terms of cost/efficacy, varies between 5817 and 13,930
euros per responder at 48 weeks, for DT and TDF/FTCRAL
respectively. DT is the most efficient regimen in the most
favourable (5503 euros per responder) and most unfavourable (6169 euros per responder) scenarios.
Conclusions: Considering the ART official Spanish prizes, the
most efficient regimen was DT, followed by the triple therapy
with non-nucleoside containing regimens. The sensitivity
analysis confirms the robustness of these findings.
References
1. Blasco AJ, Llibre JM, Arribas JR, Boix V, Clotet B, Domingo P, et al.
Analysis of costs and cost-effectiveness of preferred GESIDA/National
AIDS Plan regimens for initial antiretroviral therapy in human
immunodeficiency virus infected adult patients in 2013. Enferm
Infecc Microbiol Clin. 2013;31(9):56878.
2. Cahn P, Andrade-Villanueva J, Arribas JR, Gatell JM, Lama JR,
Norton M, et al. Dual therapy with lopinavir and ritonavir plus
lamivudine versus triple therapy with lopinavir and ritonavir plus
two nucleoside reverse transcriptase inhibitors in antiretroviraltherapy-naı̈ve adults with HIV-1 infection: 48 week results of the
randomised, open label, non-inferiority GARDEL trial. Lancet Infect
Dis. 2014;14(7):57280. doi: 10.1016/S1473-3099(14)70736-4.
P072
Prices of second-line antiretroviral treatment for middleincome countries inside versus outside sub-Saharan Africa
Bryony Simmons1; Andrew Hill2; Nathan Ford3; Kiat Ruxrungtham4
and Jintanat Ananworanich5
1
School of Public Health, Imperial College London, London,
UK. 2Molecular and Clinical Pharmacology, University of
Liverpool, Liverpool, UK. 3Department of HIV/AIDS, World Health
Organisation, Geneva, Switzerland. 4Department of Medicine,
Chulalongkorn University, Bangkok, Thailand. 5Military HIV
Research Program, Walter Reed Army Institute of Research,
Silver Spring, MD, USA.
Introduction: Antiretrovirals are available at low prices in
sub-Saharan Africa, but these prices may not be consistently
available for middle-income countries in other regions with
large HIV epidemics. Over 30% of HIV infected people live in
countries outside sub-Saharan Africa. Several key antiretrovirals are still on patent, with generic production restricted.
We assessed price variations for key antiretroviral drugs
inside versus outside sub-Saharan Africa.
Abstract P072Table 1. Comparison of the cost of antiretroviral treatment, by manufacturer and region
Manufacturer
Branded
ARV (dose)
No. of Sub-Saharan
Sub-Saharan Africa
No. of Non-Africa
Non-Africa
Price rise,
Africa countries (no.
median cost per
countries (no. of
median cost per
non-Africa vs.
of individual
person per year
individual
person per year
Sub-Saharan
transactions)
(IQR), US$
transactions)
(IQR), US$
Africa (%)
ABC (300 mg)
2 (93)
315 (294315)
3 (10)
547 (299602)
74
ATV (300 mg)
2 (170)
357 (124357)
2 (4)
1910 (19103496)
435
7 (84)
732 (732806)
9 (31)
4690 (40755717)
541
15 (492)
319 (272374)
23 (128)
720 (456932)
125
306
DRV (600 mg)
LPV/r (200
mg/50 mg)
Generic
RAL (400 mg)
3 (52)
883 (8831010)
1 (2)
3589 (35893589)
ABC (300 mg)
18 (290)
192 (167213)
33 (215)
178 (155205)
7
ATV (300 mg)
DRV (600 mg)
6 (34)
2 (2)
296 (251309)
990 (9641016)
14 (36)
1 (1)
245 (219265)
2964 (29642964)
17
199
18 (164)
391 (282429)
33 (187)
397 (349435)
2 (28)
373 (373634)
0
LPV/r (200
2
mg/50 mg)
RAL (400 mg)
77
Methods: HIV drug prices used in national programmes
(20102014) were extracted from the WHO Global Price Reporting Mechanism database for all reporting middle-income
countries as classified by the World Bank. Treatment costs
(branded and generic) were compared for countries inside
sub-Saharan Africa versus those outside. Five key second-line
antiretrovirals were analysed: abacavir, atazanavir, darunavir,
lopinavir/ritonavir, raltegravir.
Results: Prices of branded antiretrovirals were significantly
higher outside sub-Saharan Africa (p B0.001, adjusted for
year of purchase) (see Table 1). For example, the median
(interquartile range) price of darunavir from Janssen was
$732 (IQR $732-806) per person-year in sub-Saharan Africa
versus $4689 (IQR $4075-5717) in non-African middleincome countries, an increase of 541%. However, when
supplied by generic companies, most antiretrovirals were
similarly priced between countries in sub-Saharan Africa and
other regions.
Conclusions: Pharmaceutical companies are selling antiretrovirals to non-African middle-income countries at prices
74541% higher than African countries with similar gross
national incomes. However, generic companies are selling
most of these drugs at similar prices across regions. Mechanisms to ensure fair pricing for patented antiretrovirals across
both African and non-African middle-income countries need
to be improved, to ensure sustainable treatment access.
P073
Cost-effectiveness of DTGABC/3TC versus EFV/TDF/FTC
for first-line treatment of HIV-1 in the United States
Siyang Peng1; Ali Tafazzoli1; Emily Dorman1; Lisa Rosenblatt2;
Angelina Villasis-Keever3 and Sonja Sorensen1
1
Evidera, Modeling & Simulation, Bethesda, MD, USA. 2Health
Economics & Outcomes Research, Bristol-Myers Squibb Company,
Plainsboro, NJ, USA. 3HIV Medical Strategy, Bristol-Myers Squibb
Company, Plainsboro, NJ, USA.
Introduction: Data from the SINGLE trial demonstrated that
88% of treatment-naive HIV-1 patients treated with dolutegravir and abacavir/lamivudine (DTGABC/3TC) achieved
viral suppression at 48 weeks compared with 81% of patients
treated with efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC). It is unclear how this difference in
short-term efficacy impacts long-term cost-effectiveness of
these regimens. This study sought to evaluate the long-term
cost-effectiveness of DTGABC/3TC versus EFV/TDF/FTC
from a US payer perspective.
Materials and Methods: An individual discrete-event simulation model tracked the disease status and treatment pathway
of HIV-1 patients. The model simulated treatment over a
lifetime horizon by tracking change in patients’ CD4 count,
occurrence of clinical events (opportunistic infections, cancer
and cardiovascular events), treatment switch and death. The
model included up to four lines of treatment. Baseline patient
characteristics, efficacy and safety of DTGABC/3TC and EFV/
TDF/FTC were informed by data from the SINGLE trial. The
efficacy of subsequent lines of treatment, clinical event risks,
mortality, cost and utility inputs were based on literature and
expert opinion. Outcomes were lifetime medical costs, quality-
Poster Abstracts
adjusted life-years (QALYs) (both discounted at 3% per annum)
and the incremental cost-effectiveness ratio (ICER).
Results: Compared with EFV/TDF/FTC, DTGABC/3TC increased lifetime costs by $58,188 and per-person survival by
0.12 QALYs, resulting in an ICER of $482,717/QALY. In sensitivity
analyses testing conservative assumptions about EFV/TDF/
FTC’s efficacy beyond the trial period, ICERs comparing
DTGABC/3TC to EFV/TDF/FTC remained high (lowest reported ICER of $365,662/QALY). In a scenario in which the price
of EFV/TDF/FTC was reduced by 10% to reflect the potential for
price reduction as EFV goes off patent, DTGABC/3TC’s ICER
compared to EFV/TDF/FTC was $600,916/QALY. When DTG
ABC/3TC’s price was reduced by 10%, the resulting ICER
comparing DTGABC/3TC to EFV/TDF/FTC was $302,171/
QALY.
Conclusions: Compared with EFV/TDF/FTC, DTGABC/3TC
resulted in substantially higher cost, slightly better QALY over
lifetime, and ICERs far exceeding standard cost-effectiveness
thresholds, indicating that the incremental benefit in efficacy
associated with DTGABC/3TC may not be worth the
incremental increase in costs.
P074
Incremental cost per newly diagnosed HIV infection (NDHI):
routine (RTS), targeted (TTS), and current clinical practice
testing strategies (CPTS)
Cristina Gomez-Ayerbe1; Marı́a Jesús Pérez Elı́as1; Alfonso Muriel2;
Pilar Pérez Elı́as3; Agustina Cano3; Alberto Diaz1; Ana Moreno1;
Jose Luis Casado1; Cristina Santos3; Marı́a Martinez-Colubi4;
Almudena Uranga3; Fernando Dronda1 and Santiago Moreno1
1
Infectious Diseases, Hospital Ramón y Cajal, IRYCIS, Madrid, Spain.
2
Statistics Department, Hospital Ramón y Cajal, IRYCIS, Madrid,
Spain. 3Family Care, Centro de Salud Garcı́a Noblejas, Madrid, Spain.
4
Internal Medicine, Hospital de Sanchinarro, Madrid, Spain.
Introduction: Although RTS as HIV Diagnosis was considered
cost effectiveness [1], overall budget may be unaffordable for
some countries. We explore Incremental cost per NDHI
associated with different TS.
Materials and Methods: From a health care perspective,
using direct costs and Euros currency, we calculated budget
and cost per NDHI of RTS (all patients were tested), TTS
(Universal risk practices and clinical conditions-RP&CC - only
positive were tested), and CPTS (Only patients physicians
considered were tested). We considered DRIVE (Spanish
acronym of HIV infection Rapid Diagnosis) study and clinical
Practice outcomes. Population between 1860 years, attending to a Hospital Emergency Room or to a Primary Care
Center performed an HIV RP&CC questionnaire (Q) and an
HIV rapid test (HIV RT). Unitary costs considered were: HIV
RT, nurse, registry, transport and HIV confirmation when
necessary, imputed to all population in RTS and CPTS and
only in HIV RP&CC-Q positive in TTS analysis, while HIV
RP&CC-Q costs were added to all population in TTS.
Sensitivity analyses were performed with varying rates of
NDHI and of positive HIV RP&CC-Q population, and different
RP&CC Q sensitivity (SE) to predict HIV infection.
Results: 5,329 HIV RP&CC-Q and HIV RT were performed to
49.64% women, median age 37 years old, 74.9% Spaniards. In
78
DRIVE and CP, NDHI were 4.1, and 1.6, while HIV RP&CCQ was positive in 51.2%. HIV RP&CC-Q SE was 100%. Overall
budget employed in HIV testing was in RTS 43,503t, in TTS
24,472t and in CPTS 5,032t. Cost per 1 NDHI was 1,977t,
1,112t and 5,032t, respectively. A reduction in cost of 865t,
favouring TTS vs. RTS, while an increased cost of 824t in CPTS
vs. RTS was obtained. Considering NDHI rate of 2.6 saving
costs increased to 1379t in TTS, while were reduced to 576t
if NDHI rate increases 6.2. Effect of RP&CC-Q positivity rate
was similar, if 25% saving costs were 1368t, while if 75%
were reduced to 399t. Varying SE of RP&CC-Q to 95%, 91%
and 50% cost saving was 810t, 754t, and 208t, and number
of MHI one, two and 11.
Conclusions: In DRIVE study Targeted TS with universal
screening of RP&CC before an HIV rapid test is cost saving,
without missing NDHI, with respect to Routine TS. Lower
rates of HIV infection and RP&CC in the population, increase
costs savings.
Reference
1. Hayes R, Sabapathy K, Fidler S. Universal testing and treatment as
an HIV prevention strategy: research questions and methods. Current
HIV Res. 2011;9:42945.
P075
Reducing turnaround time for laboratory test results does
not improve retention of stable HIV-infected adults on POV
program: experience from Uganda
Edna Maselle1; Asaph Muhanguzi2; Simon Muhumuza2;
Jeniffer Nansubuga1; Cecilia Nawavvu1; Jeniffer Namusobya3;
Moses R. Kamya4 and Fred C. Semitala1
1
Prevention, Care and Treatment, Makerere University Joint AIDS
Program (MJAP), Kampala, Uganda. 2Monitoring and Evaluation,
Makerere University Joint AIDS Program (MJAP), Kampala, Uganda.
3
Makerere University Joint AIDS Program (MJAP), Kampala, Uganda.
4
Makerere University College of Health Sciences, Medicine, Kampala,
Uganda.
Introduction: HIV/ AIDS clinics in resource limited settings
(RLS) face increasing numbers of patients and workforce
shortage [1, 2]. To address these challenges, efficient models
of care like pharmacy only visits (POV) and nurse only visits
(NOV) are recommended [3]. The Makerere University Joint
AIDS Program (MJAP), a PEPFAR funded program providing
care to over 42,000 HIV infected adults has implemented the
POV model since 2009. In this model, stable patients on
antiretroviral therapy (ART) with adherence to ART 95%
and Karnofsky score 90% are reviewed by a doctor every
four months but visit pharmacy for ART re-fills every two
months. A study conducted in August 2011 showed low
retention on the POV program with symptomatic diseases,
pending CD4 count, complete blood count results, and poor
adherence to ART as the major reasons for the non-retention
in the POV program. To improve retention on POV, the TAT
(Turnaround Time) for laboratory results (the main reason for
non-retention in the previous study) was reduced from one
month to one week. In August 2012, the study was repeated
to assess the effect of reducing TAT on improving retention
one year after patients were placed on POV.
Poster Abstracts
Materials and Methods: A cohort analysis of data from
patients in August 2011 and in August 2012 on POV was
done. We compared retention of POV before and after
reducing the TAT for laboratory results.
Results: Retention on POV was 12.0% (95% CI 9.5014.7)
among 619 patients in 2011, (70% Females), mean age was
33 years, Standard Deviation (SD) 8.5 compared to 11.1%
(95% CI 9.1513.4) among 888 patients (70% Females),
mean age 38.3 years, SD 8.9 in 2012 (p 0.59). The main
reasons for non-retention on the POV program in 2012
were poor adherence to ART (23%) and missed clinic
appointments (14%).
Conclusions: Reducing TAT for laboratory test results did not
improve retention of stable HIV-infected adults on POV in our
clinic. Strategies for improving adherence to ART and keeping
clinic appointments need to be employed to balance workload and management of patients without compromising
quality of care, patients’ clinical, immunological and adherence outcome.
References
1. Castelnuovo B, Babigumira J, Lamorde M, Muwanga A, Kambugu
A, Colebunders R. Improvement of the patient flow in a large urban
clinic with high HIV seroprevalence in Kampala, Uganda. Int J STD
AIDS. 2009;20:1234.
2. Babigumira JB, Castelnuovo B, Lamorde M, et al. Potential impact
of task-shifting on costs of antiretroviral therapy and physician
supply in Uganda. BMC Health Serv Res. 2009;9:192. doi: 10.1186/
1472-6963-9-192.
3. World Health Organization. Task shifting to tackle health worker
shortages [cited 2012 Sep 15]. Available from: http://www.who.int/
healthsystems/task_shifting_booklet.pdf.
P076
Acceptability and confidence in antiretroviral generics
of physicians and HIV-infected patients in France
Clotilde Allavena1; Christine Jacomet2; Bruno Pereira3;
Laurence Morand-Joubert4; Haleh Bagheri5; Laurent Cotte6;
Rodolphe Garaffo7; Laurent Gerbaud8 and Pierre Dellamonica9
1
Service des Maladies infectieuses et tropicales, CHU Hôtel-Dieu,
Nantes, France. 2Service des Maladies infectieuses et tropicales, CHU
Gabriel Montpied, Clermont-Ferrand, France. 3Biostatistics Unit
(DRCI), Clermont-Ferrand University Hospital, Clermont-Ferrand,
France. 4Virology, CHU Saint-Antoine, Paris, France. 5Pharmacologie
Médicale et Clinique, CHU Toulouse, INSERM U1027, Toulouse,
France. 6Service des Maladies infectieuses et tropicales, Hospices
Civils de Lyon/INSERM U1052, Lyon, France. 7Clinical Pharmacology,
Pasteur University Hospital, Nice, France. 8Santé Publique, CHU
Clermont-Ferrand, EA 4681 PEPRADE, Clermont Université,
Clermont-Ferrand, France. 9Service des Maladies infectieuses et
tropicales, CHU de l’Archet, Nice, France.
Introduction: Switching brand name medications to generics
is recommended in France in the interest of cost effectiveness but patients and physicians are sometimes not convinced that switching is appropriate. Some antiretroviral
(ARV) generics (ZDV, 3TC, NVP) have been marketed in France
since 2013.
Materials and Methods: A multicentric cross-sectional survey
was performed in September 2013 to evaluate the perception of generics overall and ARV generics in physicians and
79
HIV-infected patients and factors associated to their acceptability. Adult HIV outpatients were asked to complete a selfquestionnaire on their perception of generics. Physicians
completed a questionnaire on the acceptability of generics
and ARV generics. Socio-demographic data, medical history
and HIV history were collected.
Results: 116 physicians in 33 clinics (68% in University
Hospital) included 556 patients (France-native 77%, active
employment 59%, covered by social Insurance 100%, homosexual/bisexual contamination 47%, median HIV duration
13 years, hepatitis coinfection 16%, on ARV therapy 95%).
Overall, patients accepted and had confidence in generics in
76% and 55% of the cases, respectively. Switching ARVs for
generics was accepted by 44% of the patients but only by 17%
if the pill burden was going to increase. 75% of the physicians
would prescribe generics, but this decreased to only 26% if
the combo had to be broken. The main reasons for nonprescription of generics were previous brand name ARVinduced side effects (35%), refusal of generics overall (37%),
lack of understanding of generics (26%), risk of non-observance of treatment (44%), anxiety (47%) and depressive
symptoms (25%). In multivariate analysis, factors associated
with the acceptability of ARV generics in patients were the use
of generics overall (p B0.001) and in physicians, the absence
of concern regarding the drug efficacy (p B0.001) and being
aware that the patient would accept generics overall (p 0.03) and ARV generics (p 0.04). No factors related to
sociodemographic conditions, HIV status or comorbidities had
a constrictive influence on the use of ARV generics.
Conclusion: Acceptability of ARV generics in this French
population is mostly dictated by the patient’s and physician’s
knowledge and use of generics overall. Switching ARV brand
name to a generic would be better accepted if the pill burden
remained unchanged.
Poster Abstracts
expiring date) in each unit, maintaining complete information
of the drug if returned when the external package is opened.
Class B - packed in blisters with complete info in the blister,
but not in unit doses, without special conservation conditions
(should be re-packed in unit doses in the pharmacy before its
dispensation to assure a class A excellence). Class C - packed in
plastic containers with complete info written only on a label
over the container, would allow repackaging only before its
initial delivery, but not when returned. Class D - drug packed
in plastic containers with manufacturer’s warning that the
product cannot be placed outside of the original package due
to special conditions of conservation (fridge, humidity) that
doesn’t allow a unit dose repackaging or reusing an opened
container. We analysed a 12-month period (July 2011-June
2012) in a hospital-based HIV outpatient pharmacy that
serves 2413 treated individuals.
Results: Patients generated 23,574 visits to pharmacy, and
received 48,325 drug packages, with 2.529.137 pills delivered. The patients suffered 1051 treatment changes for any
reason. A total amount of 122.945t in treatment were
returned to pharmacy in opened packages during the study
period. 47.139.91t would be totally lost, mainly due to being
packaged in class C and D boxes, the equivalent of treating 78
patients with rilpivirine/TDF/FTC during 1 month. Class A and
B packages in bad condition represented only 1.1% of the
cost. However, 75.805t came from returned packages in
good condition that could potentially be reused. Most of the
treatment changes were not foreseeable.
Conclusions: A significant economic budget is lost through
socially inefficient antiretroviral packages. Newer treatments
are packaged in C and D categories, therefore maintaining
these hidden costs in the near future. Any improvement in the
excellence of packaging by the manufacturer, and favouring
the choice of drugs supplied through efficient packages (when
efficacy, toxicity and convenience are similar) should minimize
the treatment expenditures paid by national health budgets.
P077
Hidden costs of HIV treatment in Spain: inefficiency of the
antiretroviral drug packaging
P078
Josep M Llibre-Codina1; Angels Andreu-Crespo2; Gloria CardonaPeitx2; Ferran Sala-Piñol2; Bonaventura Clotet-Sala1 and
Xavier Bonafont-Pujol2
1
Hospital Universitari Germans Trias i Pujol, Fundació LLuita Contra la
Sida, HIV, Barcelona, Spain. 2Hospital Universitari GermansTrias i
Pujol, Pharmacy, Barcelona, Spain.
Introduction: Antiretroviral drugs in Spain are delivered by
law only in hospital pharmacies. Commercial packages meet
variable quality standards when dispensed drugs are returned due to treatment changes or adherence problems
Nearly 2025% of the initial regimens will be changed at
48 weeks for different reasons. We evaluated the economic
impact on public health system of the inability of using
returned drugs due to inefficient packaging.
Materials and Methods: We defined socially efficient packaging as the best adapted one to being delivered in unit dose to
outpatients and classified: Class A - Drug packed in unit doses
with complete info (name of drug, dosage in mg, lot, and
The cost-effectiveness in the use of HIV counselling and
testing-mobile outreaches in reaching men who have sex
with men (MSM) in northern Nigeria
Chiedu Ifekandu1; Aliyu Suleiman2 and Ogechukwu Aniekwe3
1
HIV/Key Populations, Population Council, Abuja, Nigeria. 2HIV/Key
Populations, World Health Organization (WHO), Northern Nigeria
Region, Nigeria. 3HIV/Key Populations, African Health Project (AHP),
Abuja, Nigeria.
Introduction: Men who have sex with men (MSM) are at
increased risk of HIV and other STI infections in Nigeria. This
is because MSM are afraid to seek medical help because the
healthcare workers in various facilities are afraid of the
consequences if they provide services for MSM citing the law
as a reason not to intervene. MSM in northern states of
Nigeria are facing double-jeopardy because the few international partners working in MSM in Nigeria are pulling out of
these volatile areas because of the fear of attacks by the
Boko Haram and the Nigerian law enforcement agencies.
80
Objectives: The intervention was conducted to promote
affordable and sustainable HIV care and treatment for
MSM in Nigeria.
Methods: This intervention was conducted in the Boko Haram
ravaged cities of Kano and Maiduguri (North-East Nigeria).
Twenty MSM-key influencers from the two cities were identified and trained on HIV counselling and testing, caregivers,
case managers and on initiation process for ARV treatment for
new HIVMSM as well as ethical considerations.
Results: The mean age of the key influencers was 24 years
/-SD. Each of the trained 20 key influencers reached
20 MSM-peer with condom promotion, HCT, referral to
identified MSM-community health centers and follow-up/
caregiving within the space of one month. The project was
able to reach 400 MSM in the two cities. 89% of the peers
consented to HCT. HIV prevalence among the participants
was at 18%. The project recorded ARV-successful referral
to healthcare facilities for the respondents that tested
positive. The key influencers have been following up for
ARV-adherence.
Conclusions: Use of community members should be promoted
for sustainability and ownership. It also helps in eradicating
socio-cultural barrier to HIV intervention for MSM. Moreover,
this proves to be one of the safest and affordable methods of
reaching MSM in Nigeria in this ugly time of legalization of
homophobia in the country’s constitution.
P079
Determinants of HIV outpatient service utilization according
to HIV parameters
Paola Di Carlo1; Palmira Immordino1; Giovanni Mazzola2;
Pietro Colletti2; Ilenia Alongi1; Maurizio Mineo2; Marco Scognamillo1;
Francesco Vitale1 and Alessandra Casuccio1
1
Department of Sciences for Health Promotion and Mother-Child
Care, University of Palermo, Palermo, Italy. 2Infectious Disease Unit,
University Hospital ‘‘Paolo Giaccone’’, Palermo, Italy.
Poster Abstracts
Introduction: The increased life expectancy of HIV patients
in the era of highly active antiretroviral therapy has had
profound consequences for the healthcare systems that
provide their care. It is useful to assess whether healthcare
resources need to be adapted to the different stages of
HIV infection or to patient characteristics [1]. To study how
patient features influence utilization of out patient services,
we retrospectively analyzed the electronic health record of
HIV-positive patients who had followed day-care programs at
the AIDS Center of the University of Palermo, Italy.
Materials and Methods: 223 HIV-infected subjects were
recruited and divided into two groups according to CD4 cell
counts (117 with a CD4 count 5500/mm3 and 106 with CD4
count ]500/mm3). Data on age, gender, race, lifestyle habits
(including educational level, drug abuse history, smoking
status, alcohol consumption, sexual behaviour) BMI, HIVRNA, CD4 T-cell count, antiretroviral therapy (ART), comorbidities such as HCV co-infection, osteoporosis biomarker,
dyslipidemia, diabetes, renal function and systolic and diastolic blood pressure were recorded in a purposely designed
database and were analyzed in relation to AIN by uni- and
multivariable logistic regression.
Results: Table 1 shows the characteristics of enrolled
patients; the average age of the recruited patients was
45.499.5 years. 163 individuals were male (73%), 26 were
immigrants (12%) and 91 (40%) were treatment-naı̈ve.
Mean day care access for laboratory tests to evaluate stage
of HIV and for treatment monitoring was 6.5 days for CD4
cell count measurements and 9.6 for HIV RNA/drugresistance testing. When patients were stratified according
to CD4 count, mean day care access for laboratory tests to
evaluate HIV stage and to monitor treatment was negatively
correlated with CD4 cell counts.
Conclusions: Only patients with CD4 counts 5500/mm3
showed higher rates of healthcare utilization; these data may
be useful for monitoring and revising implementation plans
for the different phases of HIV disease.
Selected characteristics of 223 HIV-infected patients
Variable
Age years (mean and SD)
Male/Female
BMI (kg/m2) (mean and SD)
HIV with a CD4 count
HIV with a CD4 count
5500/mm3 n 117
]500/mm3 n 106
p
45.4
84/33
45.8
79/27
ns
ns
23.4
24.6
ns
99/18
98/8
ns
20/29/10
35/22/20
ns
310
1044
///
25.728
6.669
ns
28.9
25.1
ns
Drug addiction (n)
ARV therapy (B5 years)
33
52
22
30
ns
0.014
ARV therapy (five-ten years)
17
20
ns
ARV therapy (10 years)
45
52
ns
7.0/10.1
6.2/9.4
0.045/ns
Ethnicity (n) Caucasian /African
High-risk sexual behaviors Heterosex/homosex/bisexual men
CD4 T-cell count (cells/jÌL) (mean)
HIV-RNA copies/mL (mean)
25-Hydroxyvitamin D (ng/mL)
Mean day care access for laboratory tests CD4/Viral load
81
Reference
1. Brennan A, Morley D, O’Leary AC, Bergin CJ, Horgan M.
Determinants of HIV outpatient service utilization: a systematic
review. AIDS Behav. 2014 Jun 8. [Epub ahead of print]
EVALUATION OF ARV DELIVERY AND
COVERAGE
P080
High rates of viral suppression in a cohort of HIV-positive
adults receiving ART in Ethiopian health centers irrespective
of concomitant tuberculosis
Anton Reepalu1; Taye Tolera Balcha2; Sten Skogmar1;
Zelalem Habtamu Jemal3; Erik Sturegård4; Patrik Medstrand5 and
Per Björkman1
1
Infectious Diseases Research Unit, Department of Clinical Sciences,
Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
2
Infectious Diseases Research Unit, Faculty of Medicine, Lund
University, Ministry of Health, Addis Ababa, Ethiopia, Malmö,
Sweden. 3Oromia Regional Health Bureau, Addis Ababa, Ethiopia.
4
Clinical Microbiology, Region Skåne, Regional and University
Laboratories, Malmö, Sweden. 5Department of Laboratory Medicine,
Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
Introduction: Antiretroviral therapy (ART) initiation during
treatment for tuberculosis (TB) improves survival in HIV/TB
co-infected patients. Data on ART outcome for HIV/TB coinfected patients managed in primary health care in lowincome regions is limited. We compared virological suppression
rates, mortality and retention in care in HIV-positive adults
receiving care in five Ethiopian health centres with regard to
TB co-infection.
Material and Methods: HIV-positive ART-naı̈ve adults eligible
for ART initiation were prospectively recruited from October
2011 until March 2013. At inclusion, all patients submitted
sputum for microbiological TB testing (smear microscopy,
liquid culture and PCR). Virological suppression rates after
six months of ART (VS; viral load B40 and B400 copies/mL)
with regard to TB status was the primary outcome. The impact
of HIV/TB co-infection on VS rates was determined by multivariate regression analysis. Mortality and retention in care
were analyzed by proportional hazard models.
Results: Among 812 participants (TB 158; non-TB 654), 678
started ART during the follow-up period (TB 135; non-TB 543).
Median CD4 cell counts at ART initiation were 161 cells/mL
(interquartile range [IQR], 98243) and 184 (IQR, 118256)
for TB and non-TB patients, respectively (p 0.05). No
difference in retention in care between TB and non-TB
patients was observed during follow-up; 25 (3.7%) patients
Poster Abstracts
died and 17 (2.5%) were lost to follow-up (p 0.30 and
p0.83, respectively). Overall rates of VS at six months were
72.1% ( B40 copies/mL) and 88.7% ( B400 copies/mL), with
similar results for subjects with and without TB co-infection
( B40 copies/mL: 65/92 (70.7%) vs. 304/420 (72.4%), p
0.74; B400 copies/mL: 77/92 (83.7%) vs. 377/420 (89.8%),
p0.10, respectively). CD4 cell count increase during treatment was 87 (IQR, 26178) and 103 cells/mL (IQR, 38173)
for TB and non-TB patients, respectively, with no significant
difference between the two groups (p 0.49).
Conclusions: High rates of VS were achieved in adults
receiving ART at Ethiopian health centres managed by nonphysician clinicians, with no significant difference with regard
to TB co-infection. These findings demonstrate the feasibility
of combined ART and anti-TB treatment at primary health
care level in low-income countries. This study is registered
with clinicaltrial.gov, NCT01433796.
P081
Outcomes related to 4864 pregnancies with exposure to
lopinavir/ritonavir (LPV/r)
Pat Tookey1; Claire Thorne1; Marisol Martinez-Tristani2;
Michael Norton2 and Jean van Wyk2
1
UCL Institute of Child Health, University College London, London,
UK. 2Global Pharmaceutical Research and Development, AbbVie, Inc,
North Chicago, IL, USA.
Introduction: During pregnancy, LPV/r is a common anchor
drug employed to treat the mother’s HIV-1 infection in
addition to reducing the risk of mother-to-child transmission
(MTCT). The National Study of HIV in Pregnancy and Childhood (NSHPC) conducts a comprehensive population-based
surveillance of HIV infection in pregnant women exposed to
antiretroviral therapy (ART) in the UK and Ireland; in 2003
2012 over a third of pregnancies reported to the NSHPC
involved exposure to LPV/r.
Methods: We undertook a retrospective were descriptive
analysis of individual NSHPC patient data, using pregnancy
as the unit of observation. Clinical outcomes for pregnancies
reported by June 2013, where women were exposed to LPV/r
and due to deliver between January 2003 and December
2012, are described.
Results: A total of 4864 LPV/r exposed pregnancies in 4118
women were identified. These resulted in 4702 deliveries
with 4759 live and 46 stillborn infants. Seventy five percent
of women were born in sub-Saharan Africa, 13% in the UK or
Ireland. Median maternal age at conception was 30 years.
Nine hundred and eighty (20%) pregnancies were conceived
while taking LPV/r, with a median duration of LPV/r exposure
of 270 days. A total of 3884 (80%) pregnancies initiated LPV/r
after conception, with a median duration of LPV/r exposure
Abstract P081Table 1. Viral load close to delivery, by timing of LPV/r initiation
Conceived on LPV/r (n747)
Initiated LPV/r during pregnancy (n3336)
Total (n4083)
VL B50 c/mL
91% (n 677)
69% (n2302)
73% (n 2379)
VL B1000 c/mL
98% (n 729)
93% (n3100)
94% (n 3829)
82
Poster Abstracts
Materials and Methods: We interrogated the database held
by Health Protection Scotland (HPS) that contains a record
of every VL result matched against prescribed ART. Results
were censored at the end of December 2013 and are based
on the latest attendance of patients who have been under
monitoring for at least six months. For simplicity, we have
broken the results into class of drug rather than individual
drugs for example, nucleoside reverse transcriptase inhibitor
(NRTI) rather than lamivudine, abacavir etc. The data were
analyzed using univariate Poisson regression.
Results: The anonymized records of 3302 individual patients
who attended in 11 separate regions were scrutinized. Sixtyeight different combinations of antiretroviral regimes were
identified. The prescribing patterns for the five most frequently prescribed regimes in the four largest clinics are
shown in Table 1, along with the overall percentage of patients
with undetectable VL. A higher proportion of patients in
Scotland who are prescribed regimes of NRTI 2 or NRTI/
NtRTI plus PI have detectable VL but this is not statistically
significant. Although the percentage of patients with VL B50
varies between regions 1 and 4 versus regions 2 and 3, this is
also not statistically significant.
Conclusions: Overall, a high proportion of Scottish patients
on ART have undetectable VL. Patterns of ART prescribing in
Scotland do vary by region but there are no significant
differences in outcome with regard to undetectable VL. There
is a non-significant trend which may be accounted for by
differing levels of PI prescribing.
P082
of 107 days. Viral load (VL) close to delivery was available
for 4083/4702 (87%) deliveries, with VL B50 c/mL in 73%
and B1000 c/mL in 94% of women. VL by timing of
LPV/r initiation is shown in Table 1. Sixty three percent of
deliveries were by C-section, of which 62% were classified as
elective and 38% as emergency. Among singleton liveborn
infants, 13% were born prior to 37 weeks gestation (2.5%
B32 weeks) and 15% had birth weight B2500 g (2.3%
B1500 g). HIV infection status was available for 4039 (89%)
singleton infants. For the periods 20032007 and 2008
2012, MTCT rates were 1.1% (95% CI 0.61.6) and 0.5%
(95% CI 0.20.8) respectively. Hundred and thirty four live
born children (2.8%) had at least one congenital abnormality
reported.
Conclusions: In the NSHPC database, in women exposed to
LPV/r during pregnancy in the UK and Ireland, MTCT rates
are low and continue to decline, and are similar to rates in
the entire NSHPC cohort of women with diagnosed HIV [1].
The congenital abnormality rate is comparable with that
reported for the uninfected population in this geographic
region.
Reference
1. Townsend CL, Byrne L, Cortina-Borja M, Thorne C, de Ruiter A,
Lyall H, et al. Earlier initiation of ART and further decline in motherto-child HIV transmission rates, 20002011. AIDS Care. 2014;28(7):
104957.
Results from a national treatment database does it
matter which ART combination is prescribed in the real
world?
1
P083
Determinants of HIV-1 drug resistance in treatment-naı̈ve
patients and its clinical implications in an antiretroviral
treatment program in Cameroon
2
Gordon Scott and Lesley Wallace
1
Sexual Health, Chalmers Sexual Health Centre, Edinburgh, UK.
2
Epidemiology, Health Protection Scotland, Glasgow, UK.
Alexander Zoufaly1; Johannes Jochum2; Raffaela Hammerl3;
Nilofar Nassimi3; Yurika Raymond4; Gerd-Dieter Burchard3;
Stefan Schmiedel2; Jan-Felix Drexler5; Campbell Naomi Kay6,7;
Nchang Taka8; Charles Awasom8; Karin Metzner6,7; van Lunzen Jan9
and Torsten Feldt10
1
Medical Department, Kaiser Franz Josef Hospital, Vienna, Austria.
2
Medical Department, University Medical Center HamburgEppendorf, Hamburg, Germany. 3Clinical Research Unit, Bernhard
Nocht Institute for Tropical Medicine, Hamburg, Germany. 4Day
Hospital at Regional Hospital Bamenda, Bamenda, Cameroon.
5
Institute for Virology, University of Bonn, Bonn, Germany. 6Division
of Infectious Diseases, University Hospital Zurich, Zurich, Switzerland.
Introduction: Clinical trials frequently show differences in
viral load (VL) response between antiretroviral therapy (ART)
regimes. Patterns of prescribing vary from country to country
(Mocroft et al. Infection 2014 Jun 6 [epub ahead of print]),
and are likely to vary between individual clinics. Scotland has
a national database that records VL results and specific ART
regimes for every patient under care, thus allowing different
prescribing patterns between clinical centres to be monitored. Does this reveal any difference in achievement of
undetectable VL?
Regional patterns of prescribing
NRTI2 PI (%)
NRTI 2 NNRTI (%)
NRTI/NtRTI/PI (%)
NRTI/NtRTI/NNRTI (%)
NRTI/NtRTI/II (%)
% VL B 50
Region 1
Region 2
7
6
6
14
16
9
61
35
1
5
91
96
Region 3
3
11
5
38
5
96
Region 4
4
4
25
47
8
87
Scottish total
5
11
11
41
5
95
83
7
Hospital Epide, Zurich, Switzerland. 8Medical Department, Regional
Hospital Bamenda, Bamenda, Cameroon. 9Infectious Diseases Unit,
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
10
Clinic for Gastroenterology, University Hospital Duesseldorf,
Duesseldorf, Germany.
Introduction: Facing the rapid scale-up of antiretroviral
treatment (ART) programs in resource-limited settings, monitoring of treatment outcome is essential in order to timely
detect and tackle drawbacks [1].
Methods: In a prospective cohort study, 300 consecutive
patients starting first-line ART were enrolled between 2009
and2010 in a large HIV treatment centre in rural Cameroon.
Patients were followed up for 12 months. Virologic failure
was defined as a VL 1000 cop/mL at month 12. Besides
CD4 and viral load (VL) analysis, HIV-1 drug resistance testing
was performed in patients with VL1000 copies (c)/mL
plasma. In those patients and controls, minority HIV-1 drug
resistance mutations at baseline, and plasma drug levels were
analyzed in order to identify the risk factors for virologic
failure.
Results: Most enrolled patients (71%) were female. At baseline
median CD4 cell count was 162/mL (IQR 59-259), median log10
VL was 5.4 (IQR 5.05.8) c/mL, and one-third of patients
had World Health Organisation (WHO) stage 3 or 4; 30 patients
died during follow-up. Among all patients who completed
follow-up 38/238 had virologic failure. These patients were
younger, had lower CD4 cell counts and more often had WHO
stage 3 or 4 at baseline compared to patients with VL B1000c/
mL. Sixty-three percent of failing patients (24/38) had at least
one mutation associated with high-level drug resistance. The
M184V mutation was the most frequently detected nucleoside
reverse transcriptase inhibitor (NRTI) mutation (n 18) followed by TAMs (n 5) and multi-NRTI resistance mutations
(n 4).The most commonly observed non-nucleoside reversetranscriptase inhibitor (NNRTI) resistance mutations were
K103N (n 10), Y181C (n 7), and G190A (n 6). Drug resistance mutations at baseline were detected in 12/65 (18%)
patients, in 6 patients with and 6 patients without virological
failure (p=0.77). Subtherapeutic NNRTI levels (OR 6.67,
95% CI 1.9822.43, pB0.002) and poorer adherence (OR
1.54, 95% CI 1.002.39, p0.05) were each associated with
higher risk of virologic failure in the matched pair analysis.
Unavailability of ART at the treatment centre was the single
most common cause (37%) for incomplete adherence in these
patients.
Conclusions: Virologic failure after one year of first-line ART in
rural Cameroon was not associated with transmitted drug
resistance, but with reduced drug plasma levels and incomplete adherence. Strategies to assure adherence and uninterrupted drug supply are important factors for therapy
success.
Reference
1. WHO. Consolidated guidelines on general HIV care and the use of
antiretroviral drugs for treating and preventing HIV infection:
recommendations for a public health approach. WHO Library
Cataloguing-in-Publication Data, Switzerland; 2013.
Poster Abstracts
P084
Reduced HIV symptoms and improved health-related
quality of life correlate with better access to care for HIV-1
infected women: the ELLA study
Robert Baran1; Fiona Mulcahy2; Ivanka Krznaric3; Antonella d’Arminio
Monforte4; Anna Samarina5; He Xi6; Isabel Cassetti7; Jose Valdez
Madruga8; Woodie Zachry9; Jean van Wyk9 and Marisol Martinez9
1
Global Health Economics Outcomes Research, AbbVie, North
Chicago, IL, USA. 2Infectious Diseases, St James Hospital, Dublin,
Ireland. 3Infectious Disease Department, Medical Center for
Infectious Diseases Berlin (MIB), Berlin, Germany. 4Clinic of Infectious
and Tropical Diseases, San Paolo Hospital, University of Milan, Milan,
Italy. 5Infectious Disease Department, Saint-Petersburg HIV Centre,
Saint Petersburg, Russian Federation. 6Infectious Disease
Department, Guangzhou 8th People’s Hospital, Guangzhou, China.
7
Infectious Diseases, Helios Salud, Buenos Aires, Argentina. 8DST/
AIDS, Centro de Referência e Treinamento, São Paulo, Brazil.
9
Medical Affairs, AbbVie, North Chicago, IL, USA.
Introduction: Global HIV-1 prevalence is 35.3 million [1];
women comprise 50% of those infected. The majority of
women may lack regular care and only one-fourth are
virologically suppressed [2]. ELLA is a cross-sectional, noninterventional study conducted across Europe, Latin America,
Canada and Asia that describes barriers to care for HIV-infected
women and associations with disease stage, symptoms and
health-related quality of life (HRQoL).
Methods: HIV-infected women eligible for ELLA ( ]18 years)
completed: Barrier to Care Scale (BACS) comprising 12 items
in four domains (Index range 012, Overall range 14,
greatermore barriers, Overall score ]2 considered
severe); AIDS Clinical Trials Group (ACTG) Health Status
Assessment comprising 21 items assessing 9 HRQoL domains
(range 0100, greaterbetter); and ACTG Symptom Distress
Module comprising 20 symptoms rated on bother (range
04, greatermore bother). Healthcare providers documented medical history and HIV clinical data. Correlations
of BACS response and last reported VL/CD4 count with HIV
symptoms and HRQoL were analyzed. Spearman rank order
was used to test correlations with statistical significance set
at pB0.05.
Results: Enrollment: 1931 women from 30 countries; mean
age 40 years (16.9% 50 years); 47.7% education B12
years; 36% unemployed; 82.9% urban residence. HIV was
acquired heterosexually in 83.0%; 88.2% of subjects were on
ART; 57.5% had VL B50 c/ml; mean CD4 was 540.5 c/mL.
Mean [SD] BACS Index and Overall scores were 6.19 [3.47]
(N 1818) and 2.09 [0.71] (N 1922), respectively. Stigma
was a prominent barrier. Lower (better) BACS Index and
Overall scores correlated with better HRQoL on all nine
domains (p B0.0001). Lower VL and greater CD4 count were
both correlated with better HRQoL for eight of nine domains
(p B0.04, p50.0002, respectively) excepting pain. Lower
BACS Index and Overall scores correlated with fewer symptom
count and less symptom bother (p B0.0001). Fewer symptom
count and less symptom bother correlated with better HRQoL
on all nine domains (p B0.0001). While greater CD4 count
correlated with fewer HIV symptoms and less bother (p B
0.0001), VL did not significantly correlate with either.
Conclusions: In HIV-infected women, reduced barriers to care
correlated with fewer symptoms, less symptom bother and
84
better HRQoL. Improved HRQoL may be mediated by greater
CD4 counts and fewer symptoms. Better access to care may
improve HRQoL outcomes in this population.
References
1. http://www.unaids.org/en/media/unaids/contentassets/documents/
epidemiology/2013/gr2013/201309_epi_core_en.pdf Slide Presentation. September 2013.
2. Centers for Disease Control (CDC). HIV in the United States: the
stages of care; Fact Sheet. CDC, USA; July 2012.
Poster Abstracts
schemes of early diagnosis and approaches to treatment of
this disease. A large number of deaths (24%) of patients
receiving ART for more than a year, highlight the necessity for
changes to existing treatment regimen in HIV patients, with
the possibility of the development of viral resistance to
certain drugs and taking into account the latest international
experience in the treatment of HIV-infected patient.
P086
P085
Stigma reduces and social support increases engagement in
medical care among persons with HIV infection in St.
Petersburg, Russia
Analysis of causes of death among HIV-infected patients of
Kiev Regional AIDS Center during 2013
1
2
Tetiana Stepchenkova ; Olena Martynenko and
Oleksandr Yurchenko3
1
Virological, National Medical Academy of Post-graduate Education,
Kiev, Ukraine. 2Ambulatory, Kiev Regional AIDS Center, Kiev, Ukraine.
3
Kiev Regional AIDS Center, Kiev, Ukraine.
Ukraine is a leader in Europe in the prevalence of HIV
infection. There are up to 270 thousand people, who are living
with HIV. Since 1987, in Ukraine, 33,149 HIV-infected people
died. During the first six months of 2013, of all the dead,
who were suffering from HIV and in need of antiretroviral
treatment (ART) at the time of death, 41% received treatment
and only 5.7% received ART for more than one year.
Specialists of Kiev Regional AIDS Center analyzed mortality
among the patients of the centre, in order to determine the
most frequent cause of death, set the group most at risk and
to develop effective measures to reduce mortality among HIVinfected patients. In Kiev AIDS Center, 10,000 people are
under medical observation and 4004 of them are taking ART.
During 2013, 305 persons died: 217 were women and 88 were
men which included 3 children under 14 years. Most of the
dead 272 (89%) were aged 2549. Among the total number
of the dead, 125 people (41%) were receiving ART, 53 of them
(17%) were receiving ART for at least one year and 39 of them
(13%) were receiving ART for less than one month. Hundred
and fifty-eight people (52%) required ART and 22 (7%) did not
need therapy. Hundred and ninety-two patients (63%) were in
four clinical stage of HIV infection. Hundred and ten of them
had HIVTB co-infection. Twenty patients died due to TB and
12 patients died due to hepatitis b virus/hepatitis c virus
(HBV/HCV). Among these patients, 87 people (39%) were
taking ART and 136 persons (61%) were in need of ART, but
did not get it. Nineteen patients were diagnosed with cancer.
Sixteen patients, who were co-infected HIVTB had a CD4
cell count of more than 300. Based on this analysis, we can
conclude that the main causes of high mortality among HIVinfected patients in 2013 were late diagnosis of HIV, besides a
large number (52%) of patients, who were in need of ART did
not take it. A large number (40%) among those who died were
patients co-infected with HIVTB, HIVHBV/HCV. This
reinforces the necessity to introduce new schemes for the
integrated treatment of these patients, including patients
with MDR, XDR TB. Also all HIV-infected patients who died in
2013, were diagnosed multiple pathology of various organs,
which demonstrates the necessity of the introduction of
Jeffrey Kelly1; Yuri Amirkhanian1; Alexey Yakovlev2;
Vladimir Musatov2; Anastasia Meylakhs3; Anna Kuznetsova3 and
Nikolay Chaika4
1
Center for AIDS Intervention Research (CAIR), Medical College of
Wisconsin, Milwaukee, WI, USA. 2Department of Medicine, St.
Petersburg State University, St. Petersburg, Russian Federation.
3
Interdisciplinary Center for AIDS Research (ICART), Botkin Hospital
for Infectious Diseases, St. Petersburg, Russian Federation.
4
Information, St. Petersburg Pasteur Institute, St. Petersburg, Russian
Federation.
Introduction: The proportion of people living with HIV (PLH)
in care and on antiretroviral therapy (ART) in Russia is lower
than in Sub-Saharan Africa [1]. This is undoubtedly due to a
variety of systems and structural issues related to poor
treatment access, linkage and care delivery models. However,
little research has explored the reasons that PLH are not in
care from their own perspectives. This information can help
to guide the development of approaches for improving HIV
care engagement in the country.
Materials and Methods: In-depth interviews were undertaken with 80 PLH in St. Petersburg who had never been in
HIV medical care, had previously been out of care, or had
always been in care. Participants were recruited through
online PLH forums and Websites, outreach needle exchange
and non-government organisation (NGO) programs, and
chain referral. The interviews elicited detailed information
about participants’ experiences and circumstances responsible for being out of care, and factors contributing to
nonretention in HIV treatment. Verbatim transcriptions of
the interviews were coded and analyzed using MAXQDA
software to identify emerging themes.
Results: Two types of care engagement barriers most often
emerged. Some related to medical services, and others to the
family and social environment. The most frequent medical
service barriers were poor treatment infrastructure conditions and access; dissatisfaction with quality of services and
medical staff; and concerns over confidentiality and HIV status
disclosure. Social barriers were fears of potential harm to
family relationships, negative consequences if status became
known at work, and public stigmatization and myths associated having an HIV status. Social support from the PLH
community and from family and close friends facilitated
care engagement, as did motivation to take care of oneself
and one’s family. Most participants also described circumstances in which engaging into HIV care was brought about
by an urgent issue (opportunistic infections) or was enforced
85
through hospitalization or imprisonment. Trust in one’s
doctor and simply not wanting to die were also common
motives.
Conclusions: Stigma was a major barrier to care engagement,
including fear that others would learn of one’s HIV status,
whether at work, in one’s family, or in the general community. By contrast, support from family, friends and the PLH
community contributed to care engagement.
Reference
1. UNAIDS. Together we will end AIDS: report preceding the
Nineteenth International Conference on AIDS. Geneva: UNAIDS;
2012.
P087
Early HIV diagnosis through use of rapid diagnosis test (RDT)
in the community and direct link to HIV care: a pilot project
for vulnerable populations in Athens, Greece
Eleni Kakalou; Vasileios Papastamopoulos; Panagiotis Ioannidis;
Kostas Papanikolaou; Ourania Georgiou and Athanasios Skoutelis
Infectious Diseases, Evangelismos General Hospital, Athens
Greece.
Introduction: An increase in the incidence of HIV new
infections among intravenous drug users (IDUs) by 1500%,
was noted in the center of Athens in 2011. Increasing
problematic drug use, homelessness, health cuts amidst the
economic crisis, have contributed to the epidemic. New cases
doubled within a year, challenging the HIV care delivery
system [1].
Materials and Methods: A pilot project funded by the
National Strategic Reference Framework (NSRF) 20072013
of the European Union (EU), was launched from August 2012
to March 2014. It was a partnership between the HIV Clinic
of Evangelismos Hospital and the NGO PRAKSIS. The project
is aimed at offering early diagnosis and comprehensive
care to hard to reach populations. RDT diagnosis through
mobile units, direct linkage to care, elimination of waiting
times, flexibility, psychosocial support and link to harm
reduction services for active IDUs were offered to the
beneficiaries.
Results: A total of 117 people enrolled in the program
following HIV RDT offered by mobile units of the NGO
PRAKSIS in community sites. Sixty-eight percent were IDUs,
12% were men who have sex with men (MSM) and 19.5%
were heterosexuals. Men were 74.3% and women were
25.6%. Country born patients were 43.5% and non-country
born patients were 56.4%. Nine people were HIV negative
but needed post-exposure prophylaxis (PEP), treatment for
Hepatitis C and one test was false positive. Two deaths
occurred and six people were deported. Of the remaining
100 patients, 84 enrolled in the care program. Of those 77%
(65/84) remain in care for three months after the end of
the project. Care retention was 73.5% (39/53) for IDUs, 91%
(10/11) for MSM, 80% (16/20) for heterosexuals, 73% (25/35)
for country born and 82% (40/49) for non-country born
individuals. Among those that remain in care, 77.7% (42/54)
with B350 CD4 are on antiretroviral therapy (ART). Among
Poster Abstracts
those on ART 90% have undetectable viral load. Mean
value of CD4 cells at enrollment was 298 cells/mm3. At follow
up, three months after the end of the program, the mean
value of CD4 cells was 464 cells/mm3.
Conclusions: The project has proven the feasibility of a novel
approach of active case finding in the community with direct
link to care. Retention to care was satisfactory as most of
those patients would not have been able to access care
through the normal ART delivery mode of the Public Health
System. However, more obstacles to care remain. Being
homeless, poor nutrition, complicated access to harm
reduction services, lack of One Stop Shop services and police
operations in the city center impede further progress
[2,3].
References
1. Paraskevis D, Nikolopoulos G, Fotiou A, Tsiara C, Paraskeva D,
Sypsa V, et al. Economic recession and emergence of an HIV-1
outbreak among drug injectors in Athens metropolitan area: a
longitudinal study. PLoS One. 2013;8(11):78941.
2. European Centre for Disease Prevention and Control. Risk
assessment on HIV in Greece. Stockholm: ECDC; 2012.
3. Mocroft A, Lundgren JD, Sabin ML, Monforte AD, Brockmeyer N,
Casabona J, et al. Risk factors and outcomes for late presentation for
HIV-positive persons in Europe: results from the Collaboration of
Observational HIV Epidemiological Research Europe Study (COHERE).
PLoS Med. 2013;10(9):1001510.
P088
HIV/AIDS mortality in a south east European country versus
a west European country
Gordana Dragovic1; Colette Smith2; Djordje Jevtovic3; Jovana Kusic3;
Dubravka Salemovic3 and Jovan Ranin3
1
Department of Pharmacology and Clinical Pharmacology, School of
Medicine, University of Belgrade, Belgrade, Serbia and Montenegro.
2
Research Department of Infection and Population H, UCL Medical
School, London, UK. 3School of Medicine, University of Belgrade and
Infectious and Tropical Diseases Hospital, Belgrade, Serbia and
Montenegro.
Introduction: Antiretroviral (ARV) treatment available in lowmiddle income countries differs as suggested in international
HIV-treatment guidelines. Thus, we compared ARV regimens
introduced as a first-line therapy, time of initiation, frequency of making combination antiretroviral therapy (cART)
switches, frequency of viral and immunological monitoring
and treatment outcome in south east European (SEE) country
(i.e. HIV Centre in Belgrade, Serbia, (HCB)) and west
European country (i.e. Royal Free Centre for HIV Medicine
at the Royal Free Hospital London, UK (RFH)).
Materials and Methods: ARV naı̈ve patients starting cART
from 2003 to 2012 were included. Comparisons of the two
cohorts were made using a chi-square test or Fisher’s exact
test for categorical variables and a Mann-Witney U test for
continuous variables. Kaplan Meier survival curves were
compared using the log rank test.
Results: Of 597 patients from HCB, 361 (61%) initiated cART
with prior AIDS diagnosed, while 337 (19%) of 1763 patients
from RFH. Average baseline CD4 T cell counts were
86
Poster Abstracts
country due to patient’s preferences and rarely due to
drug-related toxicity.
H I V - R E L AT E D I N F E C T I O N S , C O INFECTIONS AND CANCERS, ETC OPPORTUNISTIC INFECTIONS
P089
AIDS defining opportunistic infections in patients with
high CD4 counts in the combination antiretroviral therapy
(cART) era: things ain’t what they used to be
introducing cART.
Mortality in HCB and RFH after 3 years of
significantly lower in Serbia than in UK (177 cells/mm3 vs
238 cells/mm3). The total (mediana, IQR) CD4 T cell count
measurements in the first year of cART was 2 (1, 2) at the
HCB, while it was statistically significant higher at the RFH 5
(3, 7), respectively (p B0.0001). At the RFH, it appeared that
the cART switching is due to patient’s preference or toxicity
(46%), while the lack of supply and toxicity (37%) were the
most important reasons for treatment change in HCB, within
the same period of time (p B0.05). Mortality rates were
higher at the HCB versus RFH (p B0.0001). After 12, 24 and
36 months of cART, 3%, 5% and 8% of patients died in HCB,
whereas 2%, 3% and 4% of patients died in RFH, respectively
(Figure 1).
Conclusions: In south European countries, as a consequence
of low testing rate, ARV treatment is introduced at an
advanced stage of disease, having a high mortality rate as a
consequence. Switching within ARV drugs appears often
due to lack of drug supplies and frequently drug-related
toxicity in south east Europe, while in the east European
Valentin Gisler1; David Kraus2; Johannes Nemeth3; Marthe Than
Lecompte4; Laurent Merz5; Marcel Stoeckle6; Patrick Schmid7;
Enos Bernasconi8; Rainer Weber3; Matthias Cavassini5;
Alexandra Calmy4; Luigia Elzi9 and Hansjakob Furrer1
1
Department of Infectious Diseases, Bern University Hospital and
University of Bern, Bern, Switzerland. 2Department of Infectious
Diseases and ISPM, Bern University Hospital and University of Bern,
Bern, Switzerland. 3Department of Infectious Diseases, University
Hospital Zurich, Zurich, Switzerland. 4Department of Infectious
Diseases, University Hospital Geneva, Geneva, Switzerland.
5
Department of Infectious Diseases, University Hospital Lausanne,
Lausanne, Switzerland. 6Department of Infectious Diseases,
University Hospital Basel, Basel, Switzerland. 7Infectious Diseases,
Cantonal Hospital St Gall, St Gall, Switzerland. 8Infectious Diseases,
Ospedale Civico Lugano, Lugano, Switzerland. 9Department of
Infectious Diseases, University Hospital Basel, Basel, Switzerland.
Introduction: According to reports from observational databases, classic AIDS-defining opportunistic infections (ADOIs)
occur in patients with CD4 counts above 500/mL on and off
cART. Adjudication of these events is usually not performed.
However, ADOIs are often used as endpoints, for example, in
analyses on when to start cART.
Materials and Methods: In the database, Swiss HIV Cohort
Study (SHCS) database, we identified 91 cases of ADOIs that
Abstract P089Table 1. Cases of ADOIs occurring in patients with CD4 counts 500/mL according the SHCS database (Total) and
the most likely explanation for these OIs according to an in-depth chart review. Chronic HIV infection is the most likely explanation in
only a minority of cases
Opportunistic Infection
Candida esophagitis
Total
Chronic HIV with
CD4 500
Unmasking IRIS
CD4 B500
Primary HIV
Other immunodeficiency
Wrong diagnosis
30
2
0
6
5
15
2
Pneumocystis
9
1
0
6
0
1
1
chronic ulcerative HSV
4
0
0
0
0
1
3
Mycobacterium avium
2
1
1
0
0
0
0
2
1
0
0
0
0
0
complex (MAC)
Progressive multifocal
leukoencephalopathy
(PML)
Cytomegalovirus (CMV)
2
1
0
0
0
0
1
Cryptosporidiosis
1
1
0
0
0
0
0
50
7
1
0
5
17
7
Total
87
occurred from 1996 onwards in patients with the nearest
CD4 count 500/mL. Cases of tuberculosis and recurrent
bacterial pneumonia were excluded as they also occur in
non-immunocompromised patients. Chart review was performed in 82 cases, and in 50 cases we identified CD4 counts
within six months before until one month after ADOI and had
chart review material to allow an in-depth review. In these
50 cases, we assessed whether (1) the ADOI fulfilled the
SHCS diagnostic criteria (www.shcs.ch), and (2) HIV infection
with CD4 500/mL was the main immune-compromising
condition to cause the ADOI. Adjudication of cases was
done by two experienced clinicians who had to agree on the
interpretation.
Results: More than 13,000 participants were followed in
SHCS in the period of interest. Twenty-four (48%) of the
chart-reviewed 50 patients with ADOI and CD4 500/mL had
an HIV RNA B400 copies/mL at the time of ADOI. In the 50
cases, candida oesophagitis was the most frequent ADOI in
30 patients (60%) followed by pneumocystis pneumonia and
chronic ulcerative HSV disease (Table 1). Overall chronic HIV
infection with a CD4 count 500/mL was the likely explanation for the ADOI in only seven cases (14%). Other reasons
(Table 1) were ADOIs occurring during primary HIV infection
in 5 (10%) cases, unmasking IRIS in 1 (2%) case, chronic HIV
infection with CD4 counts B500/mL near the ADOI in 13
(26%) cases, diagnosis not according to SHCS diagnostic
criteria in 7 (14%) cases and most importantly other additional immune-compromising conditions such as immunosuppressive drugs in 14 (34%).
Conclusions: In patients with CD4 counts 500/ mL, chronic
HIV infection is the cause of ADOIs in only a minority of
cases. Other immuno-compromising conditions are more
likely explanations in one-third of the patients, especially in
cases of candida oesophagitis. ADOIs in HIV patients with
high CD4 counts should be used as endpoints only with much
caution in studies based on observational databases.
P090
Investigating barriers in HIV-testing oncology patients. The
IBITOP study: phase I
Laurent Merz1; Solange Peters2; Stefan Zimmermann2;
Matthias Cavassini1 and Katharine Darling1
1
Service of Infectious Diseases, Lausanne University Hospital,
Lausanne, Switzerland. 2Service of Oncology, Lausanne University
Hospital, Lausanne, Switzerland.
Background: Since the advent of combined antiretroviral
therapy (ART), the incidence of non-AIDS-defining cancers
(non-ADCs) among HIV-positive patients is rising. We previously described HIV testing rates of B5% in our oncology
centre, against a local HIV prevalence of 0.4% [1]. We have
since worked with the Service of Oncology to identify, how
HIV testing can be optimized, we have conducted a study on
investigating barriers in HIV-testing oncology patients (IBITOP) among treating oncologists and their patients.
Methods: After an initial two-month pilot study to examine
feasibility [2], we conducted the first phase of the IBITOP
Poster Abstracts
study between 1st July and 31st October 2013. Patients of
unknown HIV status, newly diagnosed with solid-organ nonAIDS-defining cancer, and treated at Lausanne University
Hospital were invited to participate. Patients were offered
HIV testing as a part of their initial oncology work-up.
Oncologist testing proposals and patient acceptance were the
primary endpoints.
Results: Of 235 patients with a new oncology diagnosis, 10
were excluded (7 with ADCs and 3 of known HIV-positive
status). Mean age was 62 years; 48% were men and 71%
were Swiss. Of 225 patients, 75 (33%) were offered HIV
testing. Of these, 56 (75%) accepted, of whom 52 (93%) were
tested. A further ten patients were tested (without documentation of being offered a test), which gave a total testing
rate of 28% (62/225). Among the 19 patients who declined
testing, reasons cited included self-perceived absence of HIV
risk, previous testing and palliative care. Of the 140 patients
not offered HIV testing and not tested, reasons were
documented for 35 (25%), the most common being previous
testing and follow-up elsewhere. None of the 62 patients HIV
tested had a reactive test.
Conclusions: In this study, one third of patients seen were
offered testing and the HIV testing rate was fivefold higher
than that of previously observed in this service. Most patients
accepted testing when offered. As HIV-positive status impacts
on the medical management of cancer patients, we recommend that HIV screening should be performed in settings,
where HIV prevalence is 0.1%. Phase II of the IBITOP study
is now underway to explore barriers to HIV screening among
oncologists and patients following the updated national HIV
testing guidelines which recommend testing in non-ADC
patients undergoing chemotherapy.
References
1. Darling KE, Hugli O, Mamin R, Cellerai C, Martenet S, Berney A,
et al. HIV Testing practices by clinical service before and after revised
testing guidelines in a Swiss University Hospital. PLoS One. 2012;7(6):
39299.
2. Darling KEA, Zimmermann S, Merz L, Peters S, Cavassini M.
Investigating barriers in HIV-testing oncology patients. The IBITOP
study. Poster presentation, EACS; Brussels; 2013.
P091
Profile and mortality outcome of patients admitted with
cryptococcal meningitis to an urban district hospital in
KwaZulu-Natal, South Africa
Benjamin Adeyemi1 and Andrew Ross2
Family Medicine, Pietermaritzburg Hospitals Complex and
University of KwaZulu-Natal, KwaZulu-Natal, South Africa. 2Family
Medicine, University of KwaZulu-Natal, KwaZulu-Natal
South Africa.
1
Introduction: Cryptococcal meningitis (CCM) is one of the
leading causes of early mortality among HIV-infected patients. This study was a part of clinical audit [1] aimed at
improving care for patients with CCM at an urban district
hospital in South Africa.
88
Methods: Clinical records of all patients (age 13 years)
admitted to the hospital with a diagnosis of CCM (based on a
positive India ink, positive cryptococcal latex agglutination
test (CLAT) or a positive culture of Cryptococcus neoformans)
between June 2011 and December 2012 were retrospectively
reviewed. Descriptive statistics and Chi-square analysis were
generated with Epi Info 7.1.2.0. 95% confidence intervals
were reported where appropriate.
Results: Of the 127 patients admitted with CCM, only
97 (76.4%) knew their HIV status. Only 44.8% (43/96) of
those who knew they were HIV positive were on antiretroviral therapy (ART). Seventeen out of 25 patients (68%)
previously treated for CCM had defaulted fluconazole and
only 60% (15/25) were on ART. Acute mortality (death within
14 days of CCM diagnosis) was 55.9% (71/127). The median
time to death from diagnosis was four days (IQR 29). The
association between CSF WBC count B20cells/mL and increased risk of death within 14 days was statistically
significant (OR 2.2; 95% CI 1.14.6, p 0.03). Patients with
heavy cryptococcal burden (reported as numerous yeasts
seen on microscopy) at diagnosis were three times more
likely to die within 14 days of diagnosis of CCM (OR 3.2; 95%
CI 0.910.7, p0.06). Even though a CD4 count B100cells/
mm3 was associated with a 1.6 times increased acute
mortality risk, the association was not statistically significant
(OR 1.6; 95% CI 0.64.6, p0.3). The role of elevated CSF
opening pressure at diagnosis was not assessed because only
two (1.6%) patients had their baseline opening pressure
measured.
Conclusions: Acute CCM-related mortality remains high. The
number of patients who do not know their HIV status, the
number of HIV positive patients not on ART, the high level of
non-adherence to fluconazole and the proportion of patients
not on ART after at least one previous CCM episode all point
to the need of developing comprehensive strategies aimed at
encouraging HIV testing and improving patient’s retention in
HIV care and support.
Poster Abstracts
Introduction: Recent clinical trials have provided clear
evidence to support early anti-retroviral therapy (ART) in
patients with HIV/TB co-infection and low CD4 counts. We
investigated how this has changed treatment and outcomes
in Singapore.
Materials and Methods: A retrospective review was performed with inpatient and outpatient records for all subjects
diagnosed with HIV/TB co-infection from 2006 to 2011
attending the Tuberculosis Control Unit, Tan Tock Seng
Hospital, Singapore. Data for subjects with a presenting
CD4 B200 cell/mm3 were extracted and split into two groups,
‘‘Delayed’’: ART more than 8/52 after starting TB treatment,
and ‘‘Early’’: ART within 8/52 of starting TB treatment.
Results: One hundred thirty-four out of 180 subjects in the
database met the inclusion criteria for this study, 89 in the
delayed group and 45 in the early. No statistically significant
differences in baseline demographics between the two groups
were identified. Both groups presented with markedly low
CD4 counts, with overall 60% B50cells/mm3. Median CD4
counts were lower in the delayed ART group (37 vs 50,
p0.015). Prevalence of other opportunistic infections at TB
diagnosis was not significantly different (20%), but TB in the
early ART group was more likely to include extra-pulmonary
disease (46% vs 57%, p0.038). Four cases were culture
negative, 2 multi-drug resistant and 10 (7.8%) were isoniazid
mono-resistant. There was a significant trend to earlier ART
with more recent TB diagnosis (p B0.001). In the first 365 days
after TB diagnosis, 11 deaths occurred in the delayed ART
group, and 0 in the early (p 0.033). A Kaplan-Meier timeto-event analysis demonstrated a clear separation in the
frequency of death or opportunistic infections at eight weeks
(Figure 1, pB0.001). Immune reconstitution disease was
significantly more likely in the early ART group, but did not
result in death (9% vs 38%, pB0.001). Treatment interruptions due to adverse drug events (ADE) developed in a median
of 25 days (IQR 1543). Interestingly, early ART was associated
with a significantly lower number of treatment interruptions
attributed to ADEs, with a higher proportion of patients
Reference
1. Adeyemi B, Ross A. Management of cryptococcal meningitis in a
district hospital in KwaZulu-Natal: a clinical audit. Afr J Prm Health
Care Fam Med. 2014. In Press.
H I V - R E L AT E D I N F E C T I O N S , C O INFECTIONS AND CANCERS, ETC TUBERCULOSIS
P092
Improved outcomes from HIV/TB co-infection in Singapore
following a switch to earlier anti-retroviral therapy
Barnaby Young1; Kalisvar Marimuthu1; Gan Suay Hong2 and
Leo Yee Sin1
1
Infectious Diseases, Tan Tock Seng Hospital, Singapore, Singapore.
2
Respiratory Medicine, Tan Tock Seng Hospital, Singapore, Singapore.
Abstract P092Figure 1. Kaplan-Meier survival curve, censored at
first event per subject. Hazard ratio for death or opportunistic
infection 8.36 in the delayed ART group (CI 95: 4.0217.36).
89
Poster Abstracts
completing two months of pyrazinamide induction (66% vs
85%, p 0.054) and rifampicin consolidation (79% vs 95%,
p0.03) after excluding resistance or death. A trend to
longer duration TB treatment was observed with delayed ART.
Conclusions: Significant improvements in HIV/TB infection
outcomes correlate with the switch to earlier ART.
mortality rate was higher in IDUs with disseminated and/or
extrapulmonary disease. IDUs are important candidates for
acquiring and transmitting HIV infection, viral hepatitis and
TB, being difficult to control due to their high-risk behaviours.
Strengthening of HIV transmission prevention strategies,
particularly in identified risk groups, is mandatory.
P093
Alarming increase in tuberculosis and hepatitis C virus (HCV)
among HIV infected intravenous drug users
Cristiana Oprea1; Irina Ianache1; Roxana Radoi1; Simona Erscoiu1;
Gratiela Tardei2; Olimpia Nicolaescu3; Maria Nica4; Petre Calistru5;
Simona Ruta6 and Emanoil Ceausu5
1
HIV, Victor Babes Clinical Hospital for Infectious and Tropical
Diseases, Bucharest, Romania. 2Laboratory of Immunology and
Virology, Victor Babes Clinical Hospital for Infectious and Tropical
Diseases, Bucharest, Romania. 3Pneumology and Tuberculosis, Victor
Babes Clinical Hospital for Infectious and Tropical Diseases,
Bucharest, Romania. 4Laboratory of Bacteriology, Victor Babes
Clinical Hospital for Infectious and Tropical Diseases, Bucharest,
Romania. 5Infectious Diseases, Victor Babes Clinical Hospital for
Infectious and Tropical Diseases, Bucharest, Romania. 6Virology,
Stefan S Nicolau Institute of Virology, Bucharest, Romania.
Introduction: In the last years, we observed an alarming
increase in the number of newly diagnosed HIV infected
intravenous drug users (IDUs) co-infected with hepatitis
viruses or with severe bacterial infections. The aim of our
study was to assess the incidence, the demographic and
clinical characteristics of IDUs diagnosed with HIV, HCV and
tuberculosis (TB).
Materials and Methods: Prospective study on HIV infected
IDUs with HCV and TB admitted in a single centre between
January 2009 and April 2014. Data were compared to a group
of HIV infected IDUs without TB. Statistical analysis was
performed using Graphpad Prism 4.01.
Results: Out of 450 HIV infected IDUs, 134 (29.7%) were
diagnosed with HIV, HCV and TB. TB incidence among IDUs
increases from 0% in 2009 to 30.2% in 2013. The TB coinfected
patients had a mean age at diagnosis of 30 [1556] years;
were in majority males, 106 (84.4%); from urban areas, 120
(89.5%); and had significantly lower education level (85% vs
68.3%, pB0.0001) and higher rates of unemployment (80%
vs 55%, p B0.0001) than those without TB. The median CD4
cell count was lower in the TB versus non TB IDUs (143 vs 472/
mm3, pB0.0001). TB infected IDUs tend to be more
frequently late presenters (59.7 vs 24.6, pB0.0001) and to
have advanced HIV disease (47.7 vs 7.59%, pB0.0001) than
those without TB. TB cultures were positive in 64 (47.7%)
patients, 3 (2.2%) had multidrug resistant TB and 2 (1.5%) had
extended drug resistance. Disseminated and/or extrapulmonary TB was diagnosed in 51 patients (38%). The overall
mortality rate was higher in TB compared to non TB IDUs
(19.4% vs 8.2%, p0.0007), disseminated TB being associated with the most severe immunosuppression (median CD4
cell count 42/mm3) and the highest mortality rate (27.4%).
Conclusions: The incidence of TB in HIV/HCV coinfected IDUs
was high and rose over the time. TB infection was more
frequent in patients with severe immunosuppression and the
H I V - R E L AT E D I N F E C T I O N S , C O INFECTIONS AND CANCERS, ETC HEPATITIS CO-INFECTION (HCV AND HBV)
P094
Telaprevir combination therapy in HCV/HIV co-infected
patients (INSIGHT study): sustained virologic response at
12 weeks final analysis
Marisa Montes1; Mark Nelson2; Pierre Marie Girard3;
Joe Sasadeusz4; Andrzej Horban5; Beatriz Grinsztejn6;
Natalia Zakharova7; Antonio Rivero8; Erkki Lathouwers9;
Katrien Janssen10; Sivi Ouwerkerk-Mahadevan10 and
James Witek10
1
HIV Unit, Internal Medicine, Hospital La Paz, Universidad Autónoma
de Madrid, IdiPAZ, Madrid, Spain. 2Chelsea and Westminster
Hospital, London, UK. 3Hôpital St Antoine, Paris, France. 4Royal
Melbourne and Alfred Hospitals, Melbourne, Australia. 5Hospital
of Infectious Diseases, Warsaw Medical University, Warsaw, Poland.
6
STD/AIDS Clinical Research Laboratory, Instituto de Pesquisa Clı́nica
Evandro Chagas, Rio de Janeiro, Brazil. 7Saint-Petersburg AIDS Center,
St Petersburg, Russian Federation. 8Hospital Universitario Reina
Sofı́a-IMIBIC, Cordoba, Spain. 9Janssen Infectious Diseases BVBA,
Beerse, Belgium. 10Janssen Research & Development LLC, Titusville,
USA.
Introduction: We report the SVR12 final analysis of a phase
3 study of telaprevir in combination with peginterferon
(P)/ribavirin (R) in HCV-genotype 1, treatment-naı̈ve and experienced patients with HCV/HIV co-infection (INSIGHT).
Materials and Methods: Patients receiving stable, suppressive HIV antiretroviral (ARV) therapy, containing atazanavir/
ritonavir, efavirenz, darunavir/ritonavir, raltegravir, etravirine
or rilpivirine, received telaprevir 750 mg q8h (1125 mg q8h
if on efavirenz) plus P (180 mg once-weekly) and R (800 mg/
day) for 12 weeks, followed by an additional 12 weeks (noncirrhotic HCV treatment-naı̈ve and relapse patients with
extended rapid viral response [eRVR]) or 36 weeks (all others)
of PR alone. Analysis was performed when all patients had
completed the follow-up visit of 12 weeks after last planned
dose.
Results: One hundred sixty-two patients were enrolled and
treated (65 efavirenz, 59 atazanavir/ritonavir, 17 darunavir/
ritonavir, 17 raltegravir, 4 etravirine). Mean age was 45 years,
78% were male, 92% were Caucasian; mean CD4 count was 687
cells/mm3. Sixty four patients (40%) were HCV treatment-naı̈ve
and 98 (60%) were treatment experienced (29 relapsers, 18
partial responders and 51 null responders). 64% were subtype
1a. 30% had bridging fibrosis (17%) or cirrhosis (13%). 19% of
patients discontinued telaprevir, including 9% due to an
adverse event (AE), 8% reaching a virologic endpoint and 2%
for other reasons (non compliance or not defined). Treatment
90
Poster Abstracts
HCV RNA viral responses (Snapshot)
Prior partial
Prior null
Treatment naı̈ve
Prior relapser
responder
responder
(N 64)
(N 29)
(N 18)
(N 51)
Undetectable HCV RNA*, n (%)
Response by eRVR
Week 4 and 12 (eRVR)
SVR12 planned (B25 IU/mL)
Response by planned treatment
duration
Planned treatment duration
(weeks)
On-treatment virologic failure
Relapse
SVR12 planned (B25 IU/mL)
Overall (N 162)
YES
NO
YES
NO
YES
NO
YES
NO
YES
NO
37
31/37
27
10/27
14
13/14
15
5/15
10
10/10
8
3/8
19
16/19
32
5/32
80
70/80
82
23/82
(84)
(37)
(93)
(33)
(100)
(38)
(84)
(16)
(88)
(28)
24
48
24
48
48
48
24 or 48
2 (5)
2 (5)
31/37
(84)
12 (44)
2 (7)
10/27
(37)
0
0
12/
13(92)
1 (6)
1 (6)
6/16
(38)
5 (28)
0
13 (72)
21 (41)
3 (6)
21 (41)
41 (25)
8 (5)
93 (57)
*HPS COBAS† Taqman† (v2.0, Roche): lower limit of quantification of 25IU/mL, limit of detection of 15IU/mL (genotype 1).
responses are shown in Table 1. There were no HIV RNA
breakthroughs. Most frequently reported (]20% patients)
AEs were pruritus 43%; fatigue 27%; rash 34%, anorectal events
30% and influenza-like illness (25%). Anemia was reported in
15% of patients; grade ]3 haemoglobin decrease occurred in
2.5% of patients. 6% of patients experienced serious AEs.
Conclusions: In this phase 3 study of HIV-infected, HCV
treatment-naı̈ve and -experienced patients, 49% achieved
eRVR and 57% reached SVR12. In patients with an eRVR,
SVR12 rates were 80%, irrespective of prior treatment
history.
P095
Monitoring renal function during combination therapy with
telaprevir in HIV/HCV co-infected patients with advanced/
fibrosis cirrhosis
Cinzia Puzzolante; Marco Vecchia; Stefano Zona; Vanni Borghi;
Giovanni Guaraldi and Cristina Mussini
Azienda Ospedaliero-Universitaria Policlinico di Modena, Divisione di
Malattie Infettive, Modena, Italy.
Introduction: Telaprevir (TVR) plus peg interferon (PEG-IFN)
and ribavirin (RBV) substantially increase treatment efficacy
for genotype 1 chronic hepatitis C virus (HCV) infection but
data about its safety in HIV patients with cirrhosis are lacking.
Our purpose was to evaluate estimated Glomerular Filtration
Rates (eGFR) variations during combination therapy in a
difficult-to-treat HIV/HCV population with advanced fibrosis/
cirrhosis through three different scores commonly used in
clinical practice: CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration), Modification of Diet in Renal Disease
(MDRD) scores (that consider gender, ethnicity, age, serum
creatinine level [SCL]) and MDRD 6 variable (that considers
the previous parameters plus blood urea nitrogen and serum
albumin). Second objective was to identify any association
between creatinin clearance and haemoglobin (Hb) variation
during combination therapy.
Materials and Methods: We conducted an observational
retrospective study including 18 HIV/HCV patients attending
our clinic who started combination therapy for HCV, including
in the analysis the first 16 weeks of therapy. Treatment
included TVR 1125 mg BID (twice a day) for 12 weeks, PEG-IFN
a-2a 180 mcg QW and RBV daily dose according to body
weight (800 mg in individuals B60 kg; 1000 mg in individuals
6075 kg; 1200 mg in individuals 75 kg). Advanced fibrosis
was defined as Metavir scoreF3 or Ishak 34 and cirrhosis
was defined as Metavir score F4 or Ishak 56 assessed by liver
biopsy or transient elastography respectively. P per trend
were assessed to evaluate any change of SCL and eGFR
(according to different formulas). Multilevel linear regression
analysis was performed to estimate factors associated with
reduction of Hb.
Results: Baseline characteristics and HCV virological responses
were collected. Figure 1 shows median SCL and eGFR trends
across follow-up period: SCR p-per-trend was 0.28, for CKD-EPI
was 0.50, for MDRD was 0.48, for MDRD-6 variables was 0.27.
Abstract P095Figure 1. Serum creatinine levels and eGFR trends
during follow-up period and hemoglobin trend during combination
therapy.
91
Poster Abstracts
Multilevel regression analysis
[95% Conf.
b
Interval]
P value
Weeks of follow-up
0.61
0.78; 0.45
B0.001
Creatinine (mg/dL)
1.98
3.63; 0.32
0.019
1.86
0.37; 3.35
0.015
Age
0.01
0.23; 0.04
0.156
BMI
0.05
0.23; 0.14
0.641
Tenofovir Disoproxil
Fumarate exposure
0.31
0.34; 0.78
0.380
Proteinuria at baseline
0.44
0.67; 0.86
0.476
Hb
Male sex
Hb trend was also assessed and a significant decrease of Hb
across follow-up (p per trend B0.001) was noted. Multilevel
regression analysis found an association between SCL and Hb
change, after adjustment for age, sex, basal BMI, tenofovir
exposure and proteinuria (assessed at baseline) as shown in
Table 1.
Conclusions: In our experience, combination therapy with
TPV in cirrhotic HIV-HCV patients did not significantly affect
renal function. As expected, Hb levels decreased during
treatment and it is likely related to RBV exposure. In multivariable analysis, reduction of Hb appeared to be related to
SCL higher levels, thus suggesting even a mild decrease of
renal function.
The effect of DCV on the pharmacokinetics (PK) of MET or
BUP/naloxone (NLX) was assessed in subjects on stable MET
or BUP.
Materials and Methods: An open-label, two-part study
assessed the effect of steady-state oral administration of
DCV on the PK of MET (Part 1, P1) or BUP/NAL (Part 2, P2).
Safety/tolerability and pharmacodynamics (PD, opioid withdrawal scales/overdose assessment) were also assessed.
Subjects (P1, N 14; P2, N11) received daily single-dose
oral MET (40120mg) or BUP/NLX (8/224/6mg) based on
their prescribed stable dose throughout, in addition to DCV
(60mg QD) on Days 29. Serial PK sampling occurred predose
and postdose till 24 hours on Day 1 (MET/BUP) and Day 10
(MET/BUP/DCV). Noncompartmental PK were derived. Geometric mean ratios (GMR) and 90% confidence intervals
(90% CI) for MET/BUP/norBUP Cmax and AUCTAU were derived
from linear mixed effects models.
Results: Subjects were aged 1939 years, mostly white (P1,
93%; P2, 100%) and male (P1, 71%; P2, 91%). All subjects
completed the study. No clinically meaningful effect was
demonstrated as the GMR and 90% CIs fell within the
prespecified interval (P1, 0.71.4; P2, 0.52.0: see Table 1).
DCV coadministration was well-tolerated: overall, six (43%)
subjects had adverse events (AEs) (all mild and resolved
without treatment). DCV had no clinically significant effect on
the PD of MET or BUP/NLX.
Conclusions: Steady-state administration of DCV 60mg QD
had no clinically meaningful effect on the PK of MET or BUP/
NLX and was generally well-tolerated, suggesting that no
dose adjustments will be required.
P096
Evaluation of drug-drug interaction between daclatasvir and
methadone or buprenorphine/naloxone
P097
Tushar Garimella1; Reena Wang1; Wen-Lin Luo1; Philip Wastall1;
Hamza Kandoussi1; Michael Demicco2; Douglas Bruce3;
Carey Hwang1; Richard Bertz1 and Marc Bifano1
1
Research & Development, Bristol-Myers Squibb, Princeton, NJ, USA.
2
Research & Development, Anaheim Clinical Trials, Anaheim, CA,
USA. 3Clinical Investigation, Yale University, New Haven, CT, USA.
Introduction: Daclatasvir (DCV) is a potent hepatitis C virus
(HCV) NS5A replication complex inhibitor with pangenotypic
(16) activity in vitro. Methadone (MET) and buprenorphine
(BUP) are opioid medications used to treat opioid addiction;
patients on HCV therapy may require MET or BUP treatment.
HCV triple therapy in co-infection HIV/HCV is not associated
with a different risk of developing major depressive
disorder
Renata Fialho1; Majella Keller2; Alex File2; Catherine Woods2;
Marco Pereira3; Elaney Yousseff4; Jeremy Tibble2; Neil Harrison5;
Martin Fisher4; Jennifer Rusted6 and Richard Whale7
1
University of Sussex and Sussex Partnership NHS Foundation Trust,
Neuropharmacology Group, Brighton, UK. 2Digestive Diseases
Centre, Brighton and Sussex University Hospitals NHS Trust, Brighton,
UK. 3University of Coimbra, Cognitive and Behavioural Centre for
Research and, Coimbra, Portugal. 4Elton John Centre, Brighton and
Sussex University Hospitals NHS Trust, Brighton, UK. 5Brighton and
Pharmacokinetic parameters and statistical comparisons
With DCV
W/O DCV
GMR
Adj. Geo. Mean
Adj. Geo. Mean
(90% CI)
R-METa
Cmax, ng/mL
103.6
96.6
1.07 (0.97, 1.18)
BUP
AUCTAU, ng h/mL
Cmax, ng/mL
1699.6
3.3
1569.8
2.5
1.08 (0.94, 1.24)
1.30 (1.03, 1.64)
AUCTAU, ng h/mL
25.1
19.2
1.31 (1.15, 1.48)
3.1
1.8
1.65 (1.38, 1.99)
42.6
26.4
1.62 (1.33, 1.96)
NORBUP
Cmax, ng/mL
AUCTAU, ng h/mL
92
Sussex Medical School, Brighton, UK. 6School of Psychology,
University of Sussex, Brighton, UK. 7Neuropharmacology Group,
Brighton and Sussex Medical School and Sussex Partnership NHS
Foundation Trust, Brighton, UK.
Introduction: Hepatitis C (HCV) treatment options have
changed with the development of direct activity antivirals
(DAAs) and the availability of triple therapies have improved
HCV cure rates. A common neuropsychiatric side effect of
pegylated-interferon and ribavirin treatment is major depressive disorder (MDD), however little is known about such
adverse events with protease inhibitor-based triple therapy.
The aim of this study was to assess the rate of MDD in
co-infected HIV HCV patients undergoing different HCV
treatments.
Methods: All participants were co-infected HIV HCV attending
the Royal Sussex County Hospital Brighton hepatology outpatient clinic between 2010 and 2014. Participants were
assessed for DSM-IV MDD and depression severity (using the
Hamilton depression scale (HAMD)) at baseline and monthly
after treatment initiation. HIV and HCV stages, genotype,
reinfection and standard demographic variables were recorded. Influence of HCV stage (acute vs. chronic) and type
of treatment (classic vs triple), emergence of MDD and
clearance outcomes were analyzed using repeated measures
and logistic regression models.
Results: Fifty participants with a mean age of 42.65 years
(SD10.32) were included; most were male (98%). The
majority had contracted HCV genotype 1 (64%) or 4 (26%).
The HCV stage and treatment groups were matched for age
and depression at baseline. No significant differences were
found on virological outcomes considering HCV stage and
treatment. From baseline to SVR, there was a significant
increase in HAMD scores, F(4,36) 10.09, pB.001; this was
not significantly influenced by HCV stage, F(4,35) 0.54,
p.708 or HCV treatment group, F(4,35) 0.60, p .664.
Those with chronic HCV were more likely to transition to MDD
than acute infection (OR 7.77, 95% CI 2.0429.54, p.003).
No differences were found for depression emergence by HCV
treatment group (OR 0.83, 95% CI 0.223.13, p.787).
Conclusions: HCV triple therapy was not associated with a
different risk of emergence of MDD versus classic treatment.
MDD should be assessed before therapy initiation and
monitored throughout treatment for any HCV treatment
regime. Future research could usefully clarify mechanisms of
MDD emergence and risk factors for this.
P098
Sexual behaviour, recreational drug use and hepatitis C
co-infection in HIV-diagnosed men who have sex with men
in the United Kingdom: results from the ASTRA study
Marina Daskalopoulou1; Alison Rodger1; Alicia Thornton1;
Andrew Phillips1; Lorraine Sherr1; Richard Gilson1;
Margaret Johnson2; Martin Fisher3; Jane Anderson4;
Jeffrey McDonnell1; Simon Edwards5; Nicky Perry3; Simon Collins6;
Sanjay Bhagani2; Andrew Speakman1; Colette Smith1 and
Fiona Lampe1
1
University College London Royal Free Hospital, London, UK. 2Royal
Free Hospital, London, UK. 3Brighton and Sussex University Hospitals,
Poster Abstracts
Brighton, UK. 4Homerton University Hospitals, London, UK. 5Central
and North West London, London, UK. 6HIVi-Base, London, UK.
Introduction: Transmission of Hepatitis C virus (HCV) among
HIV-positive men who have sex with men (MSM) in the
United Kingdom is ongoing. We explore associations between
self-reported sexual behaviours and drug use with cumulative
HCV prevalence, as well as new HCV diagnosis.
Methods: ASTRA is a cross-sectional questionnaire study
including 2,248 HIV-diagnosed MSM under care in the
United Kingdom during 20112012. Socio-demographic,
lifestyle, HIV-related and sexual behaviour data were collected
during the study. One thousand seven hundred and fifty two
( ]70%) of the MSM who consented to linkage of ASTRA
and clinical information (prior to and post questionnaire)
were included. Cumulative prevalence of HCV was defined as
any positive anti-HCV or HCV-RNA test result at any point prior
to questionnaire completion. We excluded 536 participants
with clinical records only after questionnaire completion.
Among the remaining 1,216 MSM, we describe associations
of self-reported sexual behaviours and recreational drug use
in the three months prior to ASTRA with cumulative HCV
prevalence, using modified Poisson regression with robust
error variances. New HCV was defined as any positive antiHCV or HCV-RNA after questionnaire completion. We excluded
591 MSM who reported ever having a HCV diagnosis at
questionnaire, any positive HCV result prior to questionnaire
or did not have any HCV tests after the questionnaire. Among
the remaining 1,195 MSM, we describe occurrence of new
HCV diagnosis during follow-up according to self-reported
sexual behaviours and recreational drug use three months
prior to questionnaire (Fisher’s exact test).
Results: Cumulative HCV prevalence among MSM prior to
ASTRA was 13.3% (95% CI 11.515.4). Clinic- and age-adjusted
prevalence ratios (95% CI) for cumulative HCV prevalence were
4.6 (3.16.7) for methamphetamine, 6.5 (3.512.1) for
injection drugs, 2.3 (1.63.4) for gamma hydroxybutyrate
(GHB), 1.6 (1.32.0) for nitrites, 1.7 (1.52.0) for all condomless sex (CLS), 2.1 (1.72.5) for CLS-HIV-seroconcordant, 1.3
(0.91.9) for CLS-HIV-serodiscordant, 2.0 (1.62.5) for group
sex, 1.5 (1.21.9) for more than 10 new sexual partners in the
past year. Among 1,195 MSM with 2.2 years [IQR 1.52.4]
median follow-up, there were 7 new HCV cases during 2,033
person-years at risk. Incidence was 3.5 per 1,000 person-years
(95% CI 1.67.2). New HCV was recorded in 1.3% MSM who
used methamphetamine versus 0.5% MSM who did not
(p 0.385); 3.7% MSM who injected recreational drugs versus
0.5% MSM who did not (p 0.148); 2.9% MSM who used GHB
versus 0.4% MSM who did not (p 0.003); 1.5% MSM who
used nitrites versus 0.2% MSM who did not (p 0.019); 1.1%
MSM having CLS versus 0.3% MSM who did not (p 0.084);
1.7% MSM having CLS-HIV-serodiscordant versus 0.4% MSM
who did not (p 0.069); 0.9% MSM who had CLS-HIVseroconcordant versus 0.5% MSM who did not (p 0.318);
0.8% MSM who had group sex versus 0.5% MSM who did not
(p 0.463); and 1.6% MSM with =10 new sexual partners in
the previous year versus 0.2% MSM with no or up to 9 new
partners (p 0.015).
Conclusions: Self-reported recent use of recreational and
injection drugs, condom-less sex and multiple new sexual
93
partners are associated with pre-existing HCV infection
and, with the exception of injection drugs, appear to be
predictive of new HCV co-infection among HIV-diagnosed
MSM.
P099
Hepatic safety of RPV/FTC/TDF single tablet regimen in HIV/
HCV-coinfected patients. Preliminary results of the hEPAtic
Study
Karin Neukam1; Nuria Espinosa2; Dolores Merino3; Antonio RiveroJuárez4; Ana Carrero5; Marı́a José Rı́os6; Josefa Ruiz-Morales7;
Ana Gómez-Berrocal8; Francisco Téllez9; Marta Dı́az-Menéndez10;
Antonio Collado11; Inés Pérez-Camacho12; Marcial DelgadoFernández13; Francisco Vera-Méndez14 and Juan A. Pineda15
1
Unit of Infectious Diseases and Microbiology, Hospital Universitario
de Valme, Seville, Spain. 2Service of Infectious Diseases, Hospital
Universitario Virgen del Rocı́o, Seville, Spain. 3Unit of Infectious
Diseases, Complejo Hospitalario de Huelva, Huelva, Spain. 4Unit of
Infectious Diseases, Hospital Universitario Reina Sofı́a, Instituto de
Investigación Biomédica de Córdoba (IMIBIC), Cordoba, Spain. 5Unit
of Infectious Diseases/HIV, Hospital General Universitario Gregorio
Marañón, Madrid, Spain. 6Unit of Infectious Diseases, Hospital Virgen
Macarena, Seville, Spain. 7Unit of Infectious Diseases, Hospital
Universitario Virgen de la Victoria, Malaga, Spain. 8Service of Internal
Medicine/Infectious Diseases, Hospital Universitario de la Princesa,
Madrid, Spain. 9CMU of Infectious Diseases and Microbiology,
Hospital La Lı́nea, AGS Campo de Gibraltar, La Linea de la
Concepcion, Spain. 10Internal Medicine and Infectious Diseases,
Hospital Universitario La Paz/IdiPAZ, Madrid, Spain. 11Unit of
Infectious Diseases, Hospital Torrecárdenas, Almeria, Spain. 12Unit of
Tropical Medicine, Hospital Poniente, El Ejido, Spain. 13Service of
Infectious Diseases, Hospital Regional de Málaga, Malaga, Spain.
14
Section of Infectious Medicine, Hospital Universitario Santa Lucia,
Cartagena, Spain. 15Unit of Infectious Diseases, Hospital Universitario
de Valme, Seville, Spain.
Introduction: Although hepatotoxicity related to antiretroviral treatment (ART) has become less frequent, hepatotoxic
events, such as transaminase elevations (TE), are still a
matter of concern. RPV/FTC/TDF (EPA) is a new single tablet
regimen which is widely used in real life practice. Clinical
trials showed an adequate profile of liver safety in the subpopulation of HIV/HCV-coinfected patients receiving rilpivirine. However, the number of individuals included in these
analyses is low [1]. The aim of this ongoing study is to
evaluate the incidence of TE and total bilirubin elevations
(TBE) during the first 48 weeks of EPA-based therapy in a
large population of HIV/HCV-coinfected subjects outside of
clinical trials.
Patients and Methods: This is a retrospective analysis of HIV/
HCV-coinfected subjects who started EPA at the infectious
diseases units of 14 centres throughout Spain, included as
cases. Subjects who started an ART different to EPA during
the study period at the same hospitals were selected as
controls. The primary outcome variables were grade 3 or 4 TE
and grade 4 TBE.
Results: Of the 191 patients included, 31 (16.2%) subjects
were naı̈ve to ART. Eighty-seven individuals started EPA and
the remaining ones were controls. The most common NRTI
backbone among the controls was TDF/FTC [59 (56.7%)
Poster Abstracts
patients] followed by NRTI-sparing regimens [24 (23.1%)
individuals] and ABC/3TC [17 (16.3%) subjects]. Among
controls, 67 (64.4%) started a ritonavir-boosted protease
inhibitor, mainly DRV/r [41 (39.4%) patients] followed by
ATV/r [16 (15.4%) subjects]. EFV, ETV and RAL were started in
16 (15.4%), 12 (11.5%) and 13 (12.5%) subjects, respectively.
The median (Q1Q3) follow-up was 5.79 (3.658.61) months
for the cases and 11.44 (5.812.88) months for the controls.
TE was observed in two (2.3%) cases versus five (4.8%)
controls (p 0.358), accounting for a density of incidence of
4.32/100 person-years versus 5.51/100 person-years [incidence rate difference (95% confidence interval): 1.88
( 9.956.2), p 0.354]. All TE were grade 3 and no patient
discontinued ART due to TE. None of the cases developed
TBE versus four (3.8%) controls, all of them receiving ATV/r.
Conclusions: The frequency of grade 34 TE associated with
EPA in HIV/HCV-coinfected patients under real life conditions
is very low. In addition, TE in HIV/HCV-coinfected patients
treated with EPA are usually mild and do not lead to
treatment discontinuation. TBE was not seen in patients
taking EPA. All these data confirm that EPA is safe in this
particular subpopulation.
Reference
1. Nelson M, Amaya G, Clumeck N, et al. Efficacy and safety of
rilpivirine in treatment-naive, HIV-1-infected patients with hepatitis B
virus/hepatitis C virus coinfection enrolled in the Phase III randomized,
double-blind ECHO and THRIVE trials. J Antimicrob Chemother. 2012;
67:20208.
P100
Hepatitis B virus (HBV) status of children born to HIV/HBV
co-infected women in a French hospital: a cross-sectional
study
Pierre Sellier1; Nathalie Schnepf2; Rishma Amarsy3; Sarah Maylin2;
Martin Coutellier1; Amanda Lopes1; Marie-Christine Mazeron2;
Clara Flateau4; Marjolaine Morgand1; Nicole Ciraru-Vigneron5;
Aurore Berthe6; Aude Ricbourg5; Anne-Marie Dolores-Moreno5;
Guy Simoneau1; John Evans1; Saa Souak1; Sophie Matheron4;
Stephane Mouly1; Jean-Louis Benia5; François Simon2 and
Jean-François Bergmann1
1
Internal Medicine, Hopital Lariboisière 75010, Paris, France. 2Hopital
Saint-Louis 75010, Virologie, Paris, France. 3Hopital Lariboisière
75010, Virologie, Paris, France. 4Hopital Bichat-Claude Bernard,
Service des Maladies Infectieuses et Tropicales, Paris, France.
5
Hopital Lariboisière 75010, Gynecologie-Obstetrique, Paris, France.
6
Hopital Lariboisière 75010, Pharmacie, Paris, France.
Introduction: Human Immunodeficiency Virus (HIV) MotherTo-Child-Transmission (MTCT) and prevention by combined
antiretroviral therapy (cART) have been extensively studied.
Hepatitis B Virus (HBV) MTCT from HIV/HBV co-infected
women and prevention by antiretroviral therapy with dual
activity have been poorly studied. The aim of the study was
to assess HBV MTCT from HIV/HBV co-infected women in a
developed country with a large access to cART.
Materials and Methods: HIV/HBV co-infected pregnant
women attending the Obstetrics Department from 1st
January 2000 to 1st January 2012 could be included in the
94
study (NCT02044068). Antiretroviral therapy during pregnancy, injection of immunoglobulin and/or vaccine to newborns was retrospectively recorded. We assessed HBV status
of children at least as old as two years.
Results: Forty nine (9.2%) from 530 HIV-infected women
followed in the hospital were HIV/HBV co-infected. 34
(69.4%) had given birth to 57 children in the hospital. 13
of these women (22 children) were lost-to-follow-up, 21
women (35 children) could be studied. Twenty six children
(74.3%) had HBs Ab at a protective level, 22 of them had
received immunoglobulin at birth; 24 had received a
complete vaccine schedule during the first six months of
life (with immunoglobulin in 21 cases). The women had been
given lamivudine or tenofovir/emtricitabine during eight and
nine pregnancies respectively. Eight children (22.8%) were
tested negative for HBs Ag, HBs Ab and HBc Ab: 4 (11.4%)
had received immunoglobulin and a complete vaccine
schedule; in two children, immunoglobulin was uncertain;
in one child, the vaccine schedule was incomplete; in the last
one, data about immunoglobulin and the vaccine schedule
were lacking. The women had been given lamivudine or
tenofovir/emtricitabine during five and two pregnancies
respectively. One child had HBc Ab and HBs Ab, immunoglobulin was uncertain and the vaccine schedule was incomplete. The woman had been given lamivudine during the last
trimester.
Conclusions: Three quarters of the children were protected.
HBs Ab were negative in more than a tenth of the children
who had received immunoglobulin and a complete vaccine
schedule, questioning on long-term protection and underlining the need of control.
Poster Abstracts
CT or TT, 58.6% of patients presented cirrhosis and 24.1%
presented fibrosis F3. Infection with genotype 1a was
observed in 53.4% of patients. Median baseline HCV-RNA
was 3,282,263 IU/mL (77.5% had 800,000 IU/mL). The
most commonly used antiretroviral (ARV) drugs were
tenofovir/emtricitabine [36 (62%) patients], etravirine [21
(36%) patients], abacavir/lamivudine [18 (31%) patients],
boosted protease inhibitors [16 (27.5%) patients] and
raltegravir [12 (20.6%) patients]. Of the 42 (72.4%) patients
who had received previous HCV treatment, 13.7% were null
responders, 25.8% were partial responders and 31% had
relapsed. In an ITT approach, proportions of patients with
undetectable HCV RNA were 67.8% (38/56) at TW4, 83.3%
(40/48) at TW12, 80% (36/45) at TW24, 79.4% at TW36 (31/
39) and 72% (26/36) at TW48. Fifteen (25.8%) patients
discontinued HCV therapy [8 (13.8%) because they fulfilled
stopping rules, 5 (8.6%) individuals due to adverse events
and 2 (3.4%) were lost to follow-up]. Rash associated with
TVR (grade 1) was observed in two cases (3.4%) and all the
patients showed anaemia at some point of treatment. In an
analysis by ITT in the 31 patients who had a 60 week followup after starting therapy, SVR-12 was observed in 21 (67.7%)
patients. And in the analysis by ITT in 28 patients who had
a 72 week follow-up after starting therapy, SVR-24 was
observed in 17 (60.7%) patients.
Conclusions: Response to triple therapy with TVR plus PR in
HIV/HCV-patients under real-life conditions, and therefore,
including a high proportion of difficult to treat patients, is
similar to that found in CT. The safety profile of TVR-based
therapy is also comparable to that shown in CT, with only a
rate of discontinuation of 8.6% of individuals related to
toxicity.
P101
Efficacy and tolerability of telaprevir (TVR)-based triple
therapy in HIV/HCV-coinfected patients
Ignacio De Los Santos1; Marisa Montes2; Jose Sanz-Moreno3;
Julio De Miguel3; Jesus Sanz-Sanz1; Gabriel Gaspar4 and
Laura Perez-Caballero4
1
Internal Medicine, Hospital Universitario De La Princesa, Madrid,
Spain. 2Internal Medicine, Hospital Universitario de la Paz, Madrid,
Spain. 3Internal Medicine, Hospital Universitario Principe de Asturias,
Alcala de Henares, Spain. 4Internal Medicine, Hospital Universitario
de Getafe, Getafe, Spain.
Introduction: Clinical trials (CT) on triple therapy against HCV
infection in HIV-infected patients including TVR plus pegylated interferon and ribavirin (PR) have reported considerably
higher response rates than with PR alone. This study was
aimed to evaluate the efficacy and safety of triple therapy
including TVR in HIV/HCV-coinfected patients in real-life
conditions.
Material and Methods: HIV/HCV genotype 1 patients seen at
four Hospitals in Madrid who received therapy including TVR
plus PR for at least two weeks were included. The response
was evaluated during treatment, and sustained viral response
(SVR) was evaluated 12 and 24 weeks after the end of the
treatment.
Results: Fifty-eight patients have been included; 79% male,
median age 48 y.o.; 38% were IL28B rs12979860 genotype
P102
Telaprevir or boceprevir in HIV/HCV-1 co-infected patients
in a real-life setting. Interim analysis (24 weeks).
COINFECOVA-SEICV study
Carlos Minguez1; Enrique Ortega2; Juan Flores3; Jorge Carmena4;
Mar Masiá5; Marta Montero6; Sergio Reus7; Carlos Tornero8;
Maria Jose Galindo9; Miguel Garcia-Deltoro2; Concepción Amador10;
Jose Marı́a Cuadrado11; Jorge Usó1 and Jose López-Aldeguer12
1
Internal Medicine/Infectious Diseases Unit, Hospital General
Universitario de Castellón, Castellón, Spain. 2Infectious Diseases,
Consorcio Hospital General Universitario de Valencia, Valencia, Spain.
3
Internal Medicina, Hospital Arnau de Vilanova, Valencia, Spain.
4
Internal Medicine/Infectious Diseases Unit, Hospital Universitario Dr
Peset, Valencia, Spain. 5Infectious Diseases, Hospital General
Universitario de Elche, Elche, Spain. 6Infectious Diseases, Hospital
Universitari i Politecnic La Fe, Valencia, Spain. 7Infectious Diseases,
Hospital General Universitario de Alicante, Alicante, Spain. 8Internal
Medicina, Hospital Francesc de Borja, Gandia, Spain. 9Infectious
Diseases, Hospital Clinico Universitario de Valencia, Valencia, Spain.
10
Infectious Diseases, Hospital Comarcal de la Marina Baixa,
Villajoyosa, Spain. 11Infectious Diseases, Hospital Universitario San
Juan de Alicante, Alicante, Spain. 12Internal Medicine, Hospital
Universitari i Politecnic La Fe, Valencia, Spain.
Introduction: In general, HIV co-infected patients included in
clinical trials evaluating the hepatitis C virus (HCV) therapy
with telaprevir (TVR) or boceprevir (BOC) with advanced
95
fibrosis, are scarce. We analyze data concerning the use of
these drugs in a real-life clinical setting with patients affected
by a more advanced degree of fibrosis in a Spanish cohort.
Methods: We evaluated safety and efficacy in an interim
analysis encompassing the first 24 weeks of triple therapy
with peginterferon (alfa-2a or alfa-2b), ribavirin and TVR or
BOC in an observational, multicentre study. HIV/HCV genotype 1 co-infected patients beginning therapy from January
2012 to July 2013 were included.
Results: Enrolled patients were 155 (144 patients on TVR and
11 on BOC), average age was 47 years, 83% were male. With
respect to HCV treatment, 44% were naı̈ve, 13% relapsers,
17% partial responders, 21% null responders, and in seven
patients, the previous response was unknown. All but three
(98%) were under antiretroviral therapy (ART) (other than
reverse transcriptase inhibitors, the backbone was raltegravir
43%, atazanavir 35%, and etravirine 28%). Median HCV-RNA
at baseline was 6.1 log10, 54% were cirrhotic and 38% F3.
At week 4, 93% of patients continued on therapy, 81% at
w12, and 73% at w24. Virological failure was observed more
frequently in: cirrhotic patients (19% [95% CI, 1127]) vs F3
(12% [CI, 420]); patients with TT allele of the IL28B
polymorphism (40% [CI, 1861]) vs CT (21% [CI, 1231]),
or CC (2,2% [CI, 26]); previous null responders (37.5% [CI,
2154]) vs partial responders (15.4% [CI, 129]), naı̈ve (13%
[CI, 521]) or relapsers (0% [CI, 00]); and in patients with a
genotype subtype 1a (23.6% [CI, 5776]) vs 1b (8.1% [CI,
117]). Overall, 17% had virological failure and in 8%
treatment was discontinued due to adverse events. Severe
adverse events occurred in 30 patients (19%). Haematologic
disorders were the most common type including severe
anaemia in 12 (7.7%) patients. Erythropoietin was employed
in 41 patients (26.4%) and 11 (7.1%) received blood
transfusions. Nineteen patients (12.2%) were treated with
G-CSF, and 17 (11%) with thrombopoietin-receptor agonists.
Five patients died (3.2%), three due to hepatic decompensation, one due to pneumonia and one due to pulmonary
hypertension.
Conclusions: In a real-life setting, therapy against HCV in coinfected patients with advanced liver fibrosis shows high
virologic success at 24 weeks. However, frequent haematologic disorders are observed and a close monitoring and an
intensive therapy are needed to optimize the results.
P103
Effect of HIV infection-related factors on SVR rate in HCV
treatment in HIV-infected patients
Alexey Kravchenko and Uliana Kuimova
Central Scientific Research Institute of Epidemiology, Russia AIDS
Federal Centre, Moscow, Russian Federation.
Introduction: Factors that have an effect on the rate of
sustained virological response (SVR) in chronic hepatitis C
(CHC) patients include: genotype of hepatitis C virus (HCV);
level of HCV RNA replication and rate of its reduction in the
course of treatment; original hepatic fibrosis level; genotype of Interleukin-28B (especially for Genotype 1 HCV G1);
daily ribavirin (RBV) dose. This study evaluated the effect of
Poster Abstracts
the HIV infection-related factors on the SVR rate in HCV
treatment in patients with concurrent infection (HIV/HCV).
Methods: The follow-up included 232 HIV/HCV-infected
patients. Ninety-nine of 232 patients with HIV/HCV-infection
received antiretroviral therapy (ART) for at least three
months before the initiation of the CHC treatment. Before
the HCV therapy, the median of CD4cells was 406/mm3
(with ART) and 507/mm3 (without ART). Patients received HCV treatment with pegylated interferon (PEG-IFN)
and RBV (1000/12,000 mg/day) during 2448 weeks.
Results: SVR was received in 50% of patients with G1 HCV, and
80.1% of patients with Genotypes 2/3 (G2/3; pB0.0001). The
SVR rate in the group of patients without ART was reliably
higher, 74.4% (with ART 58.6%; p0.0053). No significant
differences in the SVR rate (62.3% and 69.6%, accordingly)
were detected after the differentiation of patients based on
the initial absolute values of CD4cells count ( B350 cells/
mm3 and 350 cells/mm3). In 127 patients with the HIV/
HCV-infection, the percentage of CD4cells before the CHC
treatment was 25% and more (Group 1 [Gr. 1]), and in 105
patients 525% (Group 2 [Gr. 2]). The SVR rate for Gr. 1
patient was 74.6%, and for Gr. 2 patients 58.1% (p 0.0023).
The SVR rate in patients with G1 HCV was 56.8% (Gr. 1) and
44.2% (Gr. 2; p0.1095), whereas the rate for G2 and 3 was
85.5% and 71.7%, accordingly (p 0.0242). Forty patients in
Gr. 1 and 59 patients in Gr. 2 received ART. The comparison of
the SVR rate for these patients showed no significant
differences: 60% and 57.6%, accordingly. SVR rate in the
patients without ART demonstrated that for Gr.1 patients
(CD4 25%) was reliably higher, 82.8% (compared to Gr.2
with 58.7%; p0.0012).
Conclusions: Along with factors related to HCV and the
patient, the SVR rate in the HCV treatment with PEG-IFN and
RBV may be affected in patients with the concurrent
infection by the use of ART and original relative content of
CD4cells. The maximum SVR rate was achieved in the
patients without ART and with the CD4cells 25%
(baseline). When indicted, it is reasonable to provide HCV
treatment to HIV-infected patients as long as the percentage
of CD4cells remains high and there is no need of ART.
P104
Liver Fibrosis progression using Fibroscan in HIV/HCV
coinfected patients with undetectable HIV viral load
Laura Perez-Martinez1; Isabel Sanjoaquin2; Maria Rivero3; Desiré GilPérez4; Santiago Letona2; Carmen Irigoyen Olaiz3; Piedad Arazo4 and
Jose Ramón Blanco1
1
Infectious Diseases Department, Hospital San Pedro, Center for
Biomedical Research of La Rioja (CIBIR), Logrono, Spain. 2Infectious
Diseases, Hospital Clı́nico Universitario Lozano Blesa, Zaragoza, Spain.
3
Infectious Diseases, Hospital de Navarra, Pamplona, Spain.
4
Infectious Diseases, Hospital Universitario Miguel Servet, Zaragoza,
Spain.
Introduction: Several factors such as duration of infection,
age, male gender, consumption of alcohol, HIV infection and
low CD4 count have been associated with fibrosis progression rate. However, it is relatively scarce, the knowledge
about the liver fibrosis progression rate in HIV-infected
96
patients with undetectable HIV viral load (VL). For this
reason, we performed the present study.
Materials and Methods: Observational and multicenter study
(20082012) conducted in four hospitals of the northern
Spain. HIV/HCV (hepatitis c) virus coinfected patients ]18
years on stable combination antiretroviral therapy (cART)
( ]6 months) and with a HIV VL B50 copies/mL were
selected to analyze their liver fibrosis progression. Fibrosis
progression was assessed using a Fibroscan† (502 STEP 3
model) and measuring a basal test and a second one at least
12 months apart from baseline. This evolution was compared
with different variables such as duration of HIV/HCV coinfection, gender, age, previous treatment for HCV, HCV
genotype, CD4 lymphocyte counts and the cART employed
at the basal test.
Results: A total of 608 patients were included (median age
29.4 years, 71.7% men). Of these, 463 patients met the
inclusion criteria. In these patients, the liver fibrosis progression was nearly flat and the only variables related to a higher
liver fibrosis progression were the increasing age of the
patients (p 0.02) and the duration of the coinfection
(p 0.001). CD4 lymphocyte counts showed a tendency to
improved liver fibrosis (p 0.056).
Conclusions: In HIV/HCV coinfected patients on stable cART
and HIV undetectable VL, the increase in liver fibrosis rate
progression was nearly flat, although it was significantly
associated with the duration of the coinfection and the age of
the patient. The beneficial effects of the cART were independent of the antiretroviral drug employed. A tendency to a
lower fibrosis progression was observed in those patients
with a higher CD4 count.
P105
Evaluation of the degree of liver fibrosis and genetical
characteristics in HIV patients with spontaneous clearance
of HCV in Cartagena, Spain
Francisco Jesús Vera Méndez1; Amaya Jimeno Almazán1; Clara Smilg
Nicolás1; Begoña Alcaraz Vidal1; Onofre Martı́nez Madrid1;
Mar Alcalde Encinas1; Josena Garcı́a Garcı́a1; Lorena Martı́nez
Fernández1; Pablo Conesa Zamora2; Elena Ruiz Belmonte1;
Paloma Escribano Viñas1 and Javier Trujillo Santos1
1
Internal Medicine, Hospital Santa Lucı́a, Cartagena, Spain.
2
Molecular Genetics Unit, Hospital Santa Lucı́a, Cartagena, Spain.
Introduction: Single-nucleotide polymorphisms (SNPs) in the
region of the Interleukin 28B (IL28B) gene on chromosome
19, coding for the interferon (IFN)-l3, are involved in
hepatitis c virus (HCV), spontaneous clearance. There is little
information on the degree of liver fibrosis (LF) in HIV
patients, who have had spontaneous clearance of HCV. Our
objective in this study is to assess the degree of liver fibrosis
in this population, as well as to identify key genetic
characteristics associated with spontaneous clearance.
Materials and Methods: Retrospective descriptive study that
evaluated from 1 January 2013 to 30 May 2014, the HIV-HCV
coinfected patients in which it has been demonstrated
spontaneous clearance of HCV infection. The main variables
analyzed were (1) genetics: Haplotype determination of
genetic polymorphism SNP rs12979860 in the region of IL
Poster Abstracts
28B gene and (2) grade of LF measured in kilopascals (kPa) by
transient elastography (TE).
Results: We evaluated 205 patients with HIV and HCV
coinfection, of whom, 17 patients (8.3%), presented spontaneous clearance. Fourteen patients (82.4%) had HIV CV B20
copies/mL, while the mean CD4 cell count was 396 (SD: 245)
cells/mcL. Nine (53%) patients were analyzed for SNP
rs12979860 of IL 28B gene. Nine patients (100%) had the
CC haplotypes, and no cases of CT and TT haplotypes were
detected (p B0.001). LF was measured by TE in 12 (70.6%)
patients. The median of LF (Kpa) was 5.95 (IQR 4.78). In four
patients (33.3%) were observed significant LF (F3F4). In the
univariate analysis, no significant differences in the median
of LF (Kpa) of HIV patients with spontaneous clearance of
HCV were observed with respect to the coinfected HIV-HCV
patients with SVR to antiviral therapy (N34; median 9.6
Kpa; IQR: 10.7; p0.92) or the coinfected HIV-HCV group
who did not receive antiviral therapy (N124; median 8.5
kPa; IQR: 7.65; p0.85).
Conclusions: Spontaneous clearance of HCV in our series of
patients coinfected with HIV infection represents an uncommon clinical phenomenon. The immune status was preserved
and most patients had HIV virological suppression. In all
patients in which the IL 28B genetic polymorphism was
determined, CC haplotypes were found. The degree of LF
(Kpa) in this population was low (B9.5 Kpa) and a low
proportion of subjects showed significant LF (F3F4). No differences in the degree of LF were found in this group compared
to coinfected patients receiving HCV treatment with SVR and
compared to untreated patients coinfected with HIV-HCV.
P106
Acute hepatitis C virus (HCV) infection in the setting of HIV
coinfection: a single-centre 10-year follow-up
Patrick Ingiliz; Katharina Steininger; Marcel Schuetze; Stephan Dupke;
Andreas Carganico; Ivanka Krznaric; Andreas Wienbreyer and
Axel Baumgarten
Infectiology, Medical Center for Infectious Diseases, Berlin, Germany.
Introduction: Acute hepatitis C virus (HCV) infection has
emerged as a major cause of morbidity in the HIV-infected
population. Most guidelines recommend early treatment
with pegylated interferon and ribavirin due to higher cure
rates. The impact of acute HCV and its treatment on the
outcome of the HIV-infected population is unknown. With
new treatment options for HCV, early treatment of acute HCV
has to be questioned. Here, we report a long-term analysis
on patients with acute HCV.
Methods: Retrospective analysis from an outpatient clinic
from Berlin. All patients with the diagnosis of acute HCV
according to The European AIDS Treatment Network (NEAT)
criteria were included in the database at their date of HCV
diagnosis and followed-up until the last medical contact.
Demographic data was taken from the medical file. A fibrosis
estimation was performed using transient elastography
(Fibroscan(† ). A Fibroscan value above 7 kPa was considered
as significant fibrosis, above 12.4 kPa as liver cirrhosis. The
following outcomes were documented: (a) liver-related:
97
hepatic decompensation, cirrhosis, hepatocellular carcinoma.
(b) non-liver-related: death, myocardial infarction, AIDSdefining event, psychiatric hospitalisation.
Results: A total of 207 cases of acute HCV infection in HIVinfected patients were diagnosed between May 2002 and
September 2013. All patients were male and declared
homosexual contacts as their risk factor for having acquired
HIV. The mean age was 39 years, 162 patients (78%) were
on antiretroviral treatment, and the median CD4 cell count
was 593/mm3 (IQR 443749). At HCV diagnosis, the
highest median alanine aminotransferase (ALT) level was
408 IU/mL (159871), the HCV viral load was 800,000 IU/mL
(45x1032.8x106). 22 cases (11%) cleared their infection
spontaneously, 161 (77%) underwent interferon-based treatment. Of those treated, 58% had a sustained virological
response. 36 cases of HCV reinfection were documented. All
patients were followed-up over an interval of 806 patientyears. The median liver stiffness was 5.3 kPa (47) after a
median interval of 34 months. 33 patients developed
significant fibrosis, and 11 patients (6%) developed cirrhosis.
Nine (5%) patients died during follow-up, and 11 developed
non-liver-related endpoints. All but one deceased patients
had interferon-based treatment.
Conclusions: Severe hepatic disease and death rarely occurs
in a highly treated HCV population. As interferon-based
treatment may induce side effects, it is from now on justified
to await new HCV treatment options.
P107
Experience of acute hepatitis C and HIV co-infection
in an inner city clinic in the UK
Christopher Ward and Vincent Lee
Manchester Centre for Sexual Health, Central Manchester
University Hospitals NHS Foundation Trust, Manchester
UK.
Introduction: Acute hepatitis C infection (HCV) is increasing
in the HIV-infected population, particularly among men who
have sex with men (MSM). Patients co-infected with HCV and
HIV progress more rapidly to liver cirrhosis and are at higher
risk of hepatocellular carcinoma. We looked at our management of acute HCV to assess treatment outcome.
Materials and Methods: We performed a retrospective and
prospective case note review of HIV-HCV co-infected patients
attending a large inner city sexual health clinic from 2006-to
date. Acute HCV infections (less than six months) were
identified and data was collected on demographics, transmission and treatment outcomes. Treatment regime was 48
weeks of weight-based ribavirin and pegylated interferon a2a.
Results: Sixty-seven acute HCV infections were identified
among 142 co-infected patients, all of whom were male and
66 (98.5%) were MSM. Median age at diagnosis was 37
(range 2059) and 58 (86.6%) were White British. Sixty
patients (89.6%) were genotype 1, 3 (4.5%) were genotype
4 and 2 (3.0%) were genotype 2/3. A further 2 (3.0%) were
re-infections. A peak in new HCV diagnoses was seen in 2013
with 17 (25.4%). Route of transmission was sexual in all cases
with 13 (19.4%) also injecting drugs, pointing to mixed
Poster Abstracts
transmission routes. Nine (69.2%) of these occurred in 2013.
Nine (13.4%) patients cleared HCV themselves. Of the 58
who didn’t clear HCV, 12 (20.7%) were lost to follow up/
transferred care, 4 (6.9%) declined treatment awaiting newer
agents, and 10 (17.2%) are waiting to start. A total of 32
patients started treatment. Six (18.8%) patients are currently
on treatment and three (9.4%) await a final sustained
virological response (SVR) test. Six out of twenty-four
(25.0%) stopped treatment due to lack of response and 1
stopped due to side effects. Fifteen (62.5%) achieved SVR
and 2 (8.3%) failed to achieve SVR. Eight out of ten (80.0%)
patients who had an early virological response (EVR)
achieved SVR.
Conclusions: Our data shows good treatment outcomes for
acute HCV infection in HIV patients with an SVR rate of
62.5%. We’ve seen a steady increase in acute HCV infection,
particularly in MSM injecting party drugs. Changing risk
behaviours, particularly a rise in chem sex parties and club
drug use, along with more anonymous partners and disclosure
issues create difficulties in managing the HCV epidemic. More
education is needed to raise awareness of HCV transmission
and disclosure in our MSM population.
P108
Incidence of recent HCV infection among persons seeking
voluntary counselling and testing for HIV and sexually
transmitted infections in Taiwan
Yi-Ching Su1; Wen-Chun Liu1; Lan-Hsin Chang1; Pei-Ying Wu2;
Yu-Zhen Luo2; Cheng-Hsin Wu1; Hsin-Yun Sun1; Sui-Yuan Chang3 and
Chien-Ching Hung1
1
Internal Medicine, National Taiwan University Hospital, Taipei City,
Taiwan. 2Center for Infection Control, National Taiwan University
Hospital, Taipei City, Taiwan. 3Clinical Laboratory Sciences and
Medical Biotechnology, National Taiwan University College of
Medicine, Taipei City, Taiwan.
Introduction: The incidence of recent hepatitis C virus
infection (HCV) infection has been noted to be increasing
among men who have sex with men (MSM), especially those
with HIV infection, in several resource-rich settings. In
Taiwan, the incidence of recent HCV infection increased
from 0 in 19942000, 2.29 in 20012005 to 10.13 per 1000
person-years of follow-up (PYFU) in 20062010. In this study,
we aimed to estimate the incidence rate of recent HCV
infection among those individuals who sought voluntary
counselling and testing (VCT) service at a University Hospital.
Methods: Between May 2006 and December 2013, 18,246
tests for HIV antibody were performed among 12,143
individuals at the VCT services. A total of 2157 clients
without HIV or HCV infection at baseline were included for
estimation of incidence rate of recent HCV infection.
Antibodies to HCV were determined with a third-generation
enzyme immunoassay. A nested case-control study with four
matched controls without HCV seroconversion for one HCV
seroconverter was conducted to investigate the factors
associated with recent HCV infection. Phylogenetic analysis
was performed among the HCV strains obtained from VCT
clients and patients coinfected with HIV and HCV between
2006 and 2013.
98
Results: During the study period, 2157 clients received a total
of 8260 tests. The HCV seroprevalence at baseline was 0.3%.
Of the 2150 HCV-negative clients who contributed 5074.99
PYFU, 17 developed HCV seroconversion (incidence rate, 3.35
per 1000 PYFU; 95% CI, 1.764.94); the rate increased from
2.28 per 1000 PYFU (95% CI, 0.054.51) in 20062009, to
3.33 per 1000 PYFU (95% CI, 0.865.80) in 20102011, to
4.94 per 1000 PYFU (95% CI, 0.998.99) in 20122013. In
case-control study, HCV seroconverters were more likely to
have HIV-infected partners, recent syphilis and a Rapid
Plasma Reagin (RPR) titre of 4 or greater. In multivariate
analysis, having HIV-infected partners remained as the only
independent associated factors with HCV seroconversion
(AOR, 6.931; 95% CI, 1.06445.163). Phylogenetic analysis
revealed transmission pairs and clusters, with most clustered
sequences derived from MSM.
Conclusions: Similar to the observation among HIV-infected
patients who are not IDUs, increasing trends of recent HCV
infection also occur among the individuals who sought VCT
services in Taiwan. Having HIV-infected partners is independently associated with recent HCV seroconversion.
Poster Abstracts
(14%) pre-cirrhotic and twelve (40%) cirrhotic patients
experienced at least one LD episode: 8 vs 28 cumulative
events at five years and 2.8 vs 1.8 average years up to the first
LD episode for pre-cirrhotic vs cirrhotic. The probability of
remaining free of LD for pre-cirrhotic vs cirrhotic patients was
97% vs 78% (p 50.01) at one year; 88% vs 65% (p 50.001) at
three years and 71% vs 44% (p 50.001) at five years. Positive
correlation was found between LD and the cirrhotic stage (vs
pre-cirrhosis, p50.001), baseline AST ]100 m/L (vs B100 m/
L, p50.01) and platelet count B120 x 109/L (vs 120 x 109/
L, p50.05).
Conclusions: Cirrhosis accounts for a significant superior risk
of LD. The time up to the first LD event differed in only one
year between pre-cirrhotic and cirrhotic, standing for the
importance of a rapid treatment referral in both subgroups.
Modifiable risk factors that accelerate fibrosis are prevalent
in HIV/HCV co-infected patients. Low platelet count, elevated
AST and F4 stage predict the rapid progression to LD and the
need for early HCV treatment. Large studies are required for
further support of these results.
P109
Risk of liver decompensation assessed in HIV/HCV coinfected individuals with advanced liver fibrosis: a faster
countdown experience
Joao Pedro Alves; Susana Peres; Fernando Borges; Ana Cláudia
Miranda; Teresa Baptista; Fernando Ventura; Isabel Antunes;
Jaime Nina; Maria José Campos; Isabel Aldir and Kamal Mansinho
Serviço de Doenças Infecciosas e Medicina Tropical, Centro
Hospitalar Lisboa Ocidental Hospital de Egas Moniz, Lisboa,
Portugal.
Introduction: Cirrhosis secondary to HCV infection is expected to peak in the next decade, particularly in the HIV coinfected subgroup and has become a leading cause of
morbidity among these individuals. Efforts must be done to
estimate the risk of liver decompensation (LD) in the short
term, in order to define the appropriate time for HCV
treatment.
Materials and Methods: Retrospective observational cohort
study aimed to assess the risk of LD among a group of HIV/
HCV co-infected patients diagnosed in the past 23 years in a
central hospital of Lisbon. Inclusion criteria: (1) advanced
liver fibrosis ]F3; (2) HCV treatment naı̈ve or without
sustained virologic response (SVR). Patients had a one to five
years period of follow-up. Multiple linear regression, MannWhitney and Kendall were the statistical tests performed.
Results: From 444 HIV/HCV co-infections, 66 met the inclusion
criteria, with preponderance of male gender (82%), 3545
years of age (55%), genotype 1a (52%), a mean of 13 years of
co-infection and an AIDS stage documented in 65%, though
the majority is under antiretroviral therapy (86%) and have
TCD4 500 m/L (59%). Half (52%) showed evidence of
steatosis, many of these (41%) presenting a history of
alcoholism or overweight (BMI ]25 Kg/m2). Pre-cirrhotic
(F3 or F3/4) or cirrhotic (F4) stage was documented in 36 and
30 patients respectively. After staging, 28 (42%) initiated HCV
treatment and SVR was achieved in 8 (29%) of those. Five
P110
Plasmacytoid Dendritic cells (pDCs) in HIV-infected and HIV/
HCV-co-infected patients receiving successful treatment
Olga Khokhlova1; Ara Reizis2; Lidya Serebrovskaya1;
Natalia Gerasimova1 and Vadim Pokrovskiy1
1
The Central Institute for Epidemiology, Russian Federal Center AIDS,
Moscow, Russian Federation. 2Clinical Department of Infectious
Pathology, The Central Institute for Epidemiology, Moscow, Russian
Federation.
Introduction: Depletion of cellular pool and constant activation of plasmacytoid dendritic cells (pDCs) in HIV-infected
persons (HIV) are associated with disease progression and
manifestation of opportunistic infections. The influence of
highly-active antiretroviral treatment (HAART) and suppressed HCV-co-infection (HIV/HCV) on the extent of
these changes remains unknown.
Objective: To study parameters of pDCs in peripheral blood
of HIV and HIV/HCV patients on HAART.
Methods: Twelve uninfected with HIV or HCV volunteers
and 37 patients (12 HIV, 9 HIV/HCV and 16 HCV)
were enrolled. All HIV patients received HAART and had
undetermined HIV viral load. All HCV patients had finished
antiviral therapy (Pegasys/ribavirin) with sustained viral
response for six months and more. The pDC population was
enumerated by flow cytometry. In vitro IFN production in the
whole blood in response to pDC-specific stimulus unmethylated CpG oligonucleotides was determined by enzyme-linked
immunosorbent assay (ELISA).
Results: The percentage of pDCs of peripheral blood mononuclear cells (PBMC) in HIV/HCV was the lowest (0.089
0.02) but statistically not different from HIV (0.1590.03;
p0.11) and significantly lower than HCV (0.1790.015;
p0.4) and controls (0.2790.045; p0.03). Absolute number of pDCs in HIV on HAART (6.391.3) was not significantly
lower than the control (10.2591.75; p0.09) but in HIV/
HCV (5.191.2; p0.03), the difference was valid. IFNalpha production by pDCs in patients on HAART in HIV
99
(2.490.9 pg/ml) and in HIV/HCV (3.791 pg/ml) patients
were significantly higher than in controls (in controls IFN-alpha
production by pDCs in the native plasma was below the level
of detection (3 pg/ml), p 0.02 and p 0.0014).
Conclusions: Absolute number of pDC in HIV-positive person
on HAART with sustained viral response to treatment of HCVco-infection was lower than in HIV-mono-infected. IFN-alpha
production by pDC in HIV and in HIV/HCV patients
receiving HAART remains higher than in uninfected persons.
P111
The effects of Maraviroc on liver fibrosis in HIV/HCV
co-infected patients
Enrique Ortega Gonzalez1; Vicente Boix2; Miguel Garcia Deltoro1;
Jose Lopez Aldeguer3; Joaquin Portilla4; Marta Montero3;
Emilio Ballester Belda1; Vicente Abril1; Felix Gutierrez5;
Carlos Minguez6; Josefa Galindo7; Concepcion Benirto8;
Magdalena Garcia Rodriguez1; Livia Giner4; Puricacion Rubio1;
Jorge Uso6 and Giovanna Llerena1
1
Infectious Disease Unit, Hospital General Universitario de Valencia,
Valencia, Spain. 2Infectious Disease Unit, Hospital General
Universitario de Alicante, Valencia, Spain. 3Infectious Disease Unit,
Hospital La Fe Universitario de Valencia, Valencia, Spain. 4Infectious
Disease Unit, Hospital General Universitario de Alicante, Alicante,
Spain. 5Infectious Disease Unit, Hospital General Universitario de
Elche, Elche, Alicante, Spain. 6Infectious Disease Unit, Hospital
General Universitario de Castellon, Castellon de la Plana, Spain.
7
Infectious Disease Unit, Hospital Clinico Universitario de Valencia,
Valencia, Spain. 8Infectious Disease Unit, Hospital General de la
Marina Baja, Villajoyosa, Alicante, Spain.
Introduction: The fibrogenesis analysis in quimeric CCR1 and
CCR5 mice revealed that CCR5 mediates its pro-fibrogenic
effects in hepatic cells and promoting stellate cells. The
blockage of co-receptors could preserve the progression of
hepatic fibrosis in HIV/HCV co-infected patients.
Objective: To evaluate the beneficial effects on hepatic
fibrosis in HIV/HCV co-infected patients that are on antiretroviral therapy (ART) with CCR5 co-receptor antagonists.
Method and materials: A multicentre, retrospective pilot
study of the evaluation of hepatic fibrosis at mid- and longterm by non-invasive methods in a HIV/HCV co-infected
patients cohort in the Valencian Community (Spain) that
received ART with a CCR5 co-receptor antagonist. The cut-off
points of serum marker tests of hepatic fibrosis were: AST
to Platelet Ratio Index (APRI) B0.5 (F0F1); 1.5 F2; 2
Cirrhosis and Forns IndexB4.2 excludes fibrosis; 6.9F2
fibrosis. Inclusion criteria was established for HIV/HCV coinfected patients on ART with CCR5 co-receptor antagonists
that had no previous history of interferon and ribavirin
treatment or those who were null-responders and received
CCR5 co-receptor antagonist treatment in the previous year.
Patients with HBV infection were excluded.
Results: A total of 71 male patients (69%) were reported. A
CD4 nadir B100 cells/uL was observed in 42% of patients
and 62% (44/71) had a basal CD4 level 350 cells/uL.
According to genotypes, 50% were G-1a, 14% G-1b, 11% G-3
and 25% G-4. The median duration of treatment with
Maraviroc (MVC) was the following: 45% took it over a
year, 41% over two years and 14% over three years. Before
Poster Abstracts
starting treatment with MVC, we observed an initial fibrosis
of F0F1 in 49% of patients, F2F3 in 24% and F4 in 27%. The
medium follow-up was of 18.45 months. Progression to a
higher fibrosis level was observed in five patients, 11 patients
improved at least one stage and the others were stable over
time. There were 38 patients taking MVC over two years, 27
patients in this group (59.38%) did not modify their fibrosis, 3
patients (11%) progressed and 8 (29.62%) showed regression
of liver fibrosis in one stage.
Conclusions: The data above shows a benefit over fibrosis
progression with MVC, expressed by fibrosis serum marker
tests in HIV/HCV co-infected patients with CCR5 tropism. The
prolong treatment with MVC (over two years) has a better
effect on liver fibrosis.
P112
Safety analysis of raltegravir/truvada regimen in HIV/HCV
co-infected patients without switchback after HCV
treatment
Robert Ehret1; Hauke Walter1; Patrick Ingiliz1; Axel Baumgarten2;
Martin Obermeier1 and Ivanka Krznaric2
1
Laboratory, MIB, Berlin, Germany. 2Out Patients Clinic, MIB, Berlin,
Germany.
Introduction: Due to drug-drug interactions of HIV- and HCVspecific antivirals when initiating an HCV-therapy, the antiretroviral therapy (ART) often has to be changed. The
spectrum of applicable antiretrovirals is small, therefore
many patients were switched to raltegravir/truvada (RAL/
TVD) in our cohort. Due to the relatively low genetic barrier
of RAL, this regimen may be endangered to fail, if the NRTI
backbone is not fully active because of pre-existing NRTI
resistance. We investigated the long-term follow-up and
safety of RAL/TVD in co-infected patients after hepatitis C
virus (HCV) therapy was stopped and the protective antiretroviral effect of interferon ended.
Materials and Methods: Twenty patients initiated a directacting antiviral (DAA) containing HCV therapy (8x faldaprevir,
6x telaprevir, 2x daclatasvir and 4x simeprevir) between 11/
2011 and 01/2013. Seventeen were switched to RAL/TVD,
three patients were not treated before, but started with the
regimen. Diagnosis of HIV infection was dated between 1985
and 2010. The HI-viral suppression was monitored retrospectively to date.
Results: Thirteen of the twenty patients (65%) remained on
RAL/TVD after finishing HCV treatment, for seven patients,
no data about their ART continuation was available, after HCV
therapy had stopped. All remaining thirteen patients showed
an HI-viral load below detection limit up to date (for 15 to
22 months, median 20 months). Only for four patients,
historic resistance data were available but none showed NRTI
mutations.
Conclusions: Switch to RAL/TVD as HIV ART due to initiating
HCV therapy was safe for the observed small cohort even in
long-term follow-up without switchback or a second ART
switch. However, resistance data for the cohort was little,
showing no NRTI mutations, indicating a relatively safe
setting. Since no further data is available, physicians should
100
Poster Abstracts
keep in mind ART history, historical therapy failure and HIVresistance while switching ART to treat HCV in co-infected
patients. Further investigation in larger cohorts is needed,
especially thinking of upcoming interferon-free HCV regimen
in heavily pre-treated co-infected patients.
namely reduce the impact of low TCD4 count in co-infected
patients.
H I V - R E L AT E D I N F E C T I O N S , C O INFECTIONS AND CANCERS, ETC CANCERS
P113
Analysis of hepatitis non-treatment causes in a cohort of
HCV and HCV/HIV infected patients
Karen Pereira; Ana Cláudia Miranda; Teresa Baptista; Susana Peres;
Isabel Antunes; Fernando Ventura; Fernando Borges and
Kamal Mansinho
Infectious Diseases, CHLO, E.P.E, Hospital de Egas Moniz, Lisboa,
Portugal.
Introduction: The decision to start hepatitis C virus (HCV)
treatment and its timing remains controversial. As new
treatment regimens are approved, it is essential to identify
patients eligible for each regimen in a timed and tailored
approach. This study aims to identify the reasons to defer
treatment of chronic hepatitis C infection in both HCV and
HCV/HIV infected patients.
Material and Methods: Retrospective observational study of
a cohort of HCV chronically infected patients with or without
HIV infection, followed in an infectious disease clinic in
Lisbon. Demographic, epidemiological, clinical, immunologic
and virologic data were collected. Statistical analysis was
performed with Microsoft Office† - Excel 2012. KolmogorovSmirnov, t-test, Chi-square and correlation analysis were
performed for a significant p valueB0.05.
Results: The study included 669 patients, 225 patients
infected with HCV (group A) and 444 patients co-infected
with HCV/HIV (group B). The comparative analysis of those
groups (A vs. B) showed: mean age was 49.4 years versus
46.9 (p B0.01), mean time since HCV diagnosis was 9.5
versus 14.6 years (p 0.558) both groups shared a male
predominance and HCV acquisition due to intravenous drug
use. Regarding genotype characterization, the predominant
was 1a in both groups (p B0.01). Evaluation of IL28B
polymorphism revealed CC 15.5% (A) versus 9.45% (B)
(p B0.01). Group B mean TCD4 count was 585 cells/mL
(mean percentage 27.1%). There was spontaneous viral
clearance in 10.7% (A) versus 4.1% (B) (p B0.01). There
were treated 52.0% (A) versus 32.2% (B) patients (p B0.01).
For the untreated ones (107 group A vs 270 group B),
no reason was identified for treatment deferral in 32.5%
(A) versus 48.0% (B) patients. The most frequent reasons for
deferring treatment were: withdrawal to follow-up (33.7%),
active staging of disease (7.2%), alcohol abuse (6.0%) and
advanced age (6.0%) in group A versus low TCD4 cell count
(17.1%), loss to follow-up (7.5%), poor adherence (7.5%) and
alcohol abuse (3.2%) in group B.
Conclusions: One of the highlighted cause for treatment
deferral in both mono and co-infected patients was withdrawal to follow-up. In co-infected patients, low TCD4 cell
count and poor adherence, also gain prominence, suggesting
that strategies to improve retention in care may be needed.
Additionally, emergence of direct-acting antiviral agents is
expected to reduce these determinants in starting treatment,
P114
Incidence of cervical dysplasia and cervical cancer in women
living with HIV in Denmark: comparison with the general
population
Kristina Thorsteinsson1; Steen Ladelund2; Søren Jensen-Fangel3;
Terese Lea Katzenstein4; Isik Somuncu Johansen5; Gitte Pedersen6;
Jette Junge7; Marie Helleberg4; Merete Storgaard3; Niels Obel4 and
Anne-Mette Lebech1
1
Department of Infectious Diseases, Copenhagen University Hospital,
Hvidovre, Denmark. 2Clinical Research Center, Copenhagen
University Hospital, Hvidovre, Denmark. 3Department of Infectious
Diseases, Aarhus University Hospital, Aarhus, Denmark. 4Department
of Infectious Diseases, The National University Hospital,
Rigshospitalet, Copenhagen, Denmark. 5Department of Infectious
Diseases, Odense University Hospital, Odense, Denmark.
6
Department of Infectious Diseases, Aalborg University Hospital,
Aalborg, Denmark. 7Department of Pathology, Copenhagen
University Hospital, Hvidovre, Denmark.
Introduction: Women living with HIV (WLWH) are reportedly
at increased risk of invasive cervical cancer (ICC). WLWH in
Denmark attend the National ICC screening program less
often than women in the general population. We aimed to
estimate the incidence of cervical dysplasia and ICC in WLWH
in Denmark.
Methods: We studied a nationwide cohort of WLWH and a
cohort of age-matched females from the general population
in the period 19992010. Pathology samples were obtained
from The Danish Pathology Data Bank containing nationwide
records of all pathology specimens. The cumulative incidence
and hazard ratios (HRs) for time from inclusion to first
cervical intraepithelial neoplasia (CIN)/ICC and time from first
normal cervical cytology to first CIN/ICC were estimated.
Sensitivity analyses were performed to include prior screening outcome, screening intensity and treatment of CIN/ICC in
the interpretation of results.
Results: We followed 1,143 WLWH and 17,145 controls with
no prior history of ICC for 9,509 and 157,362 person-years.
Compared to controls, the overall incidence of CIN1 or worse
(CIN1), CIN2 and CIN3 was higher in WLWH and predicted by young age and CD4 count B200 cells/mL. In
women with normal baseline cytology, incidences of CIN1
and CIN2 were higher in WLWH. However, incidences were
comparable between WLWH and controls adherent to the
National ICC screening program.
Conclusions: Overall, WLWH develop more cervical disease
than controls. However, incidences of CIN are comparable
amongst WLWH and controls adherent to the National ICC
screening program and with a normal baseline cytology.
101
Poster Abstracts
P115
Bladder cancer in HIV-infected adults: an emerging
concern?
Sylvain Chawki1; Guillaume Ploussard2; Claire Montlahuc3;
Jérome Verine4; Pierre Mongiat-Artus2; François Desgrandchamps2
and Jean-Michel Molina1
1
Infectious Diseases, Saint Louis Hospital, Paris, France. 2Urology,
Saint Louis Hospital, Paris, France. 3Biostatistic and Medical
Information, Saint Louis Hospital, Paris, France. 4Pathology, Saint
Louis Hospital, Paris, France.
Introduction: As HIV-infected patients get older more nonAIDS-related malignancies are to be seen. Cancer now
represents almost one third of all causes of deaths among
HIV-infected patients [1]. Albeit bladder cancer is one of the
most common malignancy worldwide [2], only 13 cases of
bladder cancer in HIV-infected patients have been reported
in the literature so far [3].
Materials and Methods: We conducted a monocentric study
in our hospital. We selected all patients who were previously
admitted (from 1998 to 2013) in our hospital with diagnoses
of HIV and bladder cancer. The objective was to assess the
prevalence and characteristics of bladder cancers in HIVinfected patients in our hospital.
Results: Based on our administrative HIV database (6353
patients), we found 15 patients (0.2%) with a bladder cancer.
Patients’ characteristics are presented in Table 1. Patients
were mostly men and heavy smokers. Their median nadir CD4
cell count was below 200 and most had a diagnosis of AIDS.
A median time of 14 years was observed in those patients,
between the diagnosis of HIV-infection and the occurrence of
bladder cancer, although in patients much younger (median
age 56) than those developing bladder cancer without HIV
infection (71.1 years) [4]. Haematuria was the most frequent
diagnosis circumstance in HIV-infected patients who had
relatively preserved immune function on highly active
antiretroviral therapy (HAART). Histopathology showed relatively advanced cancers at diagnosis with a high percentage
of non transitional cell carcinoma (TCC) tumor and of TCC
with squamous differentiation, suggesting a potential role for
human papilloma virus (HPV) co-infection. Death rate was
high in this population.
Conclusions: Bladder cancers in HIV-infected patients remain
rare but occur in relatively young HIV-infected patients with a
low CD4 nadir, presenting with haematuria, most of them
being smokers, and have aggressive pathological features
that are associated with severe outcomes.
References
Abstract P115Table 1. Characteristics
Per cent or median
[IQR]
Parameters
No. of patients
15
Patients
Age at the diagnosis of HIV-infection (years)
42 [34;47]
Age at the diagnosis of cancer (years)
56 [47;61]
Male gender
Smokers (and former smokers)
73.3%
73.3%
1. Morlat P, Roussillon C, Henard S, Salmon D, Bonnet F, Cacoub P,
et al. Causes of death among HIV-infected patients in France in 2010
(national survey): trends since 2000. AIDS. 2014;28:118191.
2. Ploeg M, Aben KKH, Kiemeney LA. The present and future burden
of urinary bladder cancer in the world. World J Urol. 2009;27:
28993.
3. Gaughan EM, Dezube BJ, Bower M, Aboulafia DM, Bohac G, Cooley
TP, et al. HIV-associated bladder cancer: a case series evaluating
difficulties in diagnosis and management. BMC Urol. 2009;9:10.
4. Hinotsu S, Akaza H, Miki T, Fujimoto H, Shinohara N, Kikuchi E, et al.
Bladder cancer develops 6 years earlier in current smokers: analysis of
bladder cancer registry data collected by the cancer registration committee of the Japanese Urological Association. Int J Urol. 2009;16:649.
HIV infection
Nadir CD4 cell count (cells/mm3)
3
CD4 cell count (cells/mm )
195 [95;262]
506 [228;703]
CDC stage C at diagnosis
54.6%
% with plasma HIV RNA level B 200 cp/mL
60.0%
% on HAART at diagnosis
78.6%
Bladder cancer
Histological type
Transitional cell carcinoma
80.0%
Including urothelial carcinoma with squamous
27.3%
differentiation
Sarcomatoid carcinoma
13.3%
Epidermoid carcinoma
6.7%
T stage of the tumor
a
1
26.7%
26.7%
2
46.6%
High histological grade of tumor
69.2%
Haematuria as initial symptom
71.4%
Death due to bladder cancer
30.8%
P116
Autologous stem cell transplantation in HIV-related
lymphoma in the rituximab era a feasibility study in a
monocentric cohort
Imke Wieters1; Johannes Atta2; Gerrit Kann1; Junaid Owasil1;
Siri Goepel1; Annette Haberl1; Christoph Stephan1 and Timo Wolf1
1
Department of Infectious Diseases, HIV Center, J. W. Goethe
University Hospital, Frankfurt, Germany. 2Haematology and
Oncology, J. W. Goethe University Hospital, Frankfurt, Germany.
Introduction: Since the introduction of highly active antiretroviral therapy (HAART) [1] and later on the availability of
anti-CD20 monoclonal antibody treatment [2], the therapeutic
options as well as the prognosis of AIDS related lymphoma
(ARL) have been improved. There is however no uniform
agreement on how to treat patients who do not achieve a
partial remission, who experience a relapse or who have very
aggressive subtypes. Autologous hematopoietic stem cell
transplantation (ASCT) has become an option for those
patients. We retrospectively examined ARL patients to
102
Baseline characteristics
Ann
Gender Age
Poster Abstracts
Lymphoma
CD 4 at HIV primary
CD4 at
Viral load at
Arbor
Prior AIDS
diagnosis
lymphoma
lymphoma
ART at lymphoma
TDF/FTC/EFV
M
50
DLCL
II B
Kaposi
unknown
134
B20
M
66
DLCL (first relapse)
IV BE
no
753
2
8700000
none
M
30
Plasmablastic
IV BE
Kaposi
165
150
B20
FTC/TDF/RGV
M
36
PCNSL
n/a
Kaposi
unknown
96
817000
FTC/TDF/RGV/
M
59
DLCL
IV BE
no
171
66
36
DRV/RTV
FTC/TDF/ATV/RTV
M
36
Plasmablastic
IV BE
no
13
13
265000
non
Lymphoma
Lymphoma
M
41
DLCL (first relapse)
II
Tuberculosis
154
883
B20
ETV/MVC/DRV/
F
57
PCNSL
n/a
no
3
3
1990000
none
RTV
MMale; F Female; diffuse large cell lymphoma DLCL; primary central nervous system lymphoma (PCNSL).
elucidate the feasibility of high-dose chemotherapy and
autologous stem cell transplantation.
Patients and methods: Data of seven male and one female
HIV patients with ARL was collected and informed consent
was obtained. Age, HIV disease characteristics (CD4 count,
HIV-RNA-PCR, ART) and transplantation-related details (histopathology, myeloablative therapy, neutrophil engraftment
and NCI-CTCAE during/after transplantation as well as follow
up and survival) were obtained from the patients’ medical
records.
Results: Eight patients were treated with the intent of
ASCT. The median age was at 64 years. Four patients had
experienced prior AIDS. The median CD4 NADIR was at 157/ml,
the median CD4 count at diagnosis of lymphoma at 81/ml.
Five patients were receiving combination antiretroviral therapy (cART) at the time of lymphoma diagnosis, four of which
had achieved a viral load of less than 50/ml. Two patients have
died, due to (Nr. 8) a transplant-related complication (noninfectious leukoencephalophathy). The other patient died
of an unknown reason (351 days after transplantation). The
median survival is at 345 days to date. The time until
engraftment was well at 11 days. Grade 3/4 haematological
toxicity was present in all patients. Five out of three patients
developed infectious complications, but there were no infection-related deaths. One patients (Nr. 4) developed a Kaposi
Sarcoma reactivation that necessitated further chemotherapy.
Conclusions: ASCT is feasible in high risk ARL with good
engraftment. Toxicity was substantial and studies are needed
to define which patients have an unduly high risk of toxicity.
References
1. Wolf T, Brodt HR, Fichtlscherer S, Mantzsch K, Hoelzer D, Helm
EB, et al. Changing incidence and prognostic factors of survival in
AIDS-related non-Hodgkin lymphoma in the era of highly active
antiretroviral therapy. Leuk Lymph. 2005;46(2):20715.
2. Wyen C, Jensen B, Hentrich M, Siehl J, Sabranski M, Esser S, et al.
Treatment of AIDS-related lymphomas: rituximab is beneficial even
in severely immunosuppressed patients. AIDS. 2012;26(4):45764.
P117
Prevalence of monoclonal gammopathy in HIV patients
in 2014
Philippe Genet; Laurent Sutton; Driss Chaoui; Ahmad Al Jijakli;
Juliette Gerbe; Virginie Masse and Bouchra Wifaq
Hematology, Centre Hospitalier Victor Dupouy, Argenteuil, France.
Introduction: In non-HIV patients, Monoclonal Gammopathy
of Undetermined Significance (MGUS) is associated with an
increased risk of subsequent development of haematologic
malignancies, especially multiple myeloma (MM) and it has
been recently demonstrated that MM is always preceded
by a MGUS phase. A higher prevalence of MGUS and MM
has been observed in HIV patients compared to the general
population. Nevertheless, it has been shown that MGUS in
the context of HIV can disappear with antiretroviral therapy
(ART). So, measuring MGUS prevalence in HIV patients in the
recent period appears of special interest.
Materials and Methods: From January to June 2014, in each
out-patient seen in our unit, a serum protein electrophoresis
was performed.
Results: A total of 393 patients were screened. Eight patients
with HIV2 and one patient with HIV1HIV2 infection were
excluded. Finally, 383 patients (173 female, 210 male) with
HIV1 infection were analyzed. Characteristics of patients
were as follows: median age 42.2 years (19.179.1), hepatitis
B virus (HBV) and/or hepatitis C virus (HCV) co-infection 47
(18.8%), median CD4 610 (21758), CD8 793 (1134010),
presence of a past AIDS event for 88 patients (23%). Median
time with HIV infection was 11 years (030). Three hundred
fifty-nine patients (93.7%) were on ART for a median
duration of 105 months (0287). For 320 patients (83.6%),
viral load was below 50 viral copies/ml. Twelve cases of
MGUS (3.1%) were observed: IgG Kappa (five cases), IgG
Lambda (five cases), biclonal with two IgG Kappa (one case)
and in one case, three monoclonal immunoglobulins were
observed (IgG Kappa 2IgG Lambda). The monoclonal
immunoglobulin’s level was low and below 1 g/l in all cases
except two (2.1 and 11.6 g/l). No factor was found to be
103
Poster Abstracts
predictive of the presence of MGUS in particular age, CD4,
HBV/HCV co-infection, viral load or ART.
Conclusions: In the context of modern ART, the prevalence of
MGUS remains above those observed in the general population. Even if the level of monoclonal spike observed in our
cohort is generally low, an excess risk of subsequent development of MM could be present. Nevertheless, a prospective
follow-up of HIV patients with MGUS is necessary to
determine this risk.
P118
Haemophagocytic syndrome and elevated EBV load as
initial manifestation of Hodgkin lymphoma in a HIV patient:
case report and review of the literature
Delphine Sculier; Thanh Doco-Lecompte; Mathieu Rougemont and
Alexandra Calmy
Infectious Diseases, University Hospitals of Geneva, Geneva,
Switzerland.
Introduction: In HIV patients, haemophagocytic syndrome
(HPS) may occur in the presence of cancer, concomitant viral
infection, HIV primo-infection or at the initiation of highly
active antiretroviral therapy (HAART). Hodgkin lymphoma
remains a rare cause of HPS. We describe a case of HPS with
very high Epstein Barr virus (EBV) load in a HIV patient as
initial manifestation of Hodgkin lymphoma.
Material and Methods: A 29-year-old HIV positive man,
successfully treated with HAART with an undetectable viral
load and CD4 cells count of 438/ml, was admitted for high
fever of unknown origin. Laboratory results showed a
pancytopenia with haemoglobin at 82 g/l, lymphocyte count
at 0.36G/l and platelets count at 47G/l; a highly elevated
ferritine 7500 mg/l; increased lactate dehydrogenase at
885U/l and soluble IL2 receptor (CD25) 60 ng/ml. EBV
load was measured and confirmed at 2,600,000 copies/ml.
A PET-CT imaging showed diffuse elevated metabolic activity in the bone marrow and in two lesions in the spleen
without lymphadenopathy. Bone marrow and liver biopsies
revealed images of haemophagocytosis and lymphocyte
depleted Hodgkin lymphoma. Treatment consisted in etoposid, steroids, and R-ABVD (rituximab, doxorubicin, bleomycin,
vinblastine, dacarbazine) chemotherapy. The patient completed six cycles of chemotherapy. We reviewed the literature in PubMed with the following keywords: HPS, HIV, EBV,
Hodgkin lymphoma.
Results: We identified four publications and two reviews
reporting cases of HPS associated with Hodgkin lymphoma
in HIV patients with either a positive EBV load either the
presence of encoded EBV RNA in tumour cells. Twenty-two
cases (including one pediatric case) were described. Among
adults, mostly men, the median age was B50 years and immune suppression was marked with a median CD4 cell
count B100 cells/ml, even in patients receiving HAART.
When measured, EBV load in the serum was high. Prognosis
was poor with a high mortality despite adequate treatment
consisting in steroids and chemotherapy, with or without
etoposide (Table 1).
Conclusions: Our case report and the review of literature
suggest that physicians should be aware of the association
between EBV infection/reactivation and Hodgkin lymphoma
as a cause of HPS in HIV patients, even if successfully treated
with HAART. The pathogenesis of these three interrelated
conditions (viral infection, oncogenesis and immunologic
reaction) remains unclear.
P119
Cancer prevalence in a metropolitan HIV clinic
Eleanor Barnes1; Cara Saxon2 and Sameena Ahmad2
Reported cases of HPS associated with Hodgkin lymphoma and high EBV load in HIV patients
Number of
Encoded EBV RNA in
PCR EBV in
cases
Sex
Age (years)
CD4 count/ml
tumour cells
serum/ml
Evolution
Khagi et al. (Clin Adv
1
M
58
314
n/a
54,954
Died
Hematol Oncol 2012)
Flew et al. (Int J STD AIDS
1
M
46
40
Positive
27,000
Alive
1
M
8
90
Positive
n/a
Died
1
M
26
n/a
Positive
n/a
Died
Number of
Ratio
Median age
Median CD4
Encoded EBV RNA in
PCR EBV in
Evolution
cases
10
M/F
n/a
(years)
42 a
count/ml
91
tumor cells
n/a
serum/ml
20,000 a
Case report
2010)
Preciado et al. (Leuk
Lymphoma 2001)
Albrecht et al. (Arch Pathol
Lab Med 1997)
Review
Fardet et al. (AIDS 2010) a
Not
favourable a
Ménard et al. (Clin Infect
8
3:1 b
38 b
n/a
100% b
n/a
n/a
Dis) b
Legend: n/a: not available; a Review of 58 HPS cases, 10 associated with Hodgkin lymphoma, reported values related to the 58 cases; b Review
of 34 HPS cases associated with Hodgkin lymphoma, 8 in HIV patients, reported values related to the 8 HIV cases.
104
1
School of Medicine, University of Manchester, Manchester, UK.
Department of Sexual Medicine & HIV, University Hospitals of
South Manchester, Manchester, UK.
2
Introduction: Morbidity and mortality rates from AIDs
defining cancers have fallen significantly since the introduction of highly active antiretroviral therapy (HAART). Patients
are now living longer with HIV and are at a greater risk of
other HIV- and non-HIV related malignancies. We report what
we believe to be the first UK cancer prevalence study in the
modern HAART era.
Methods: A retrospective review of electronic clinic letters
was performed for all patients currently receiving, and those
who had died whilst receiving, their HIV care at our centre.
Demographics of patients with pre-cancerous changes, an
active or previous cancer were recorded.
Results: There were 438 active patients (369 male, 69
female) and 18 deceased patients (12 male, 6 female) in
April 2014. Thirty-six out of four hundred fifty-six (8%) cancer
diagnoses were found overall. Thirty-one out of four hundred
thirty-eight (7%) diagnoses in active patients and 5/18 (28%)
in deceased patients. More than half of those diagnosed with
cancer were aged 50 or over (17/31 [55%]). In active patients
17/31 (55%) were AIDs defining cancers, with the most
common type of cancer diagnosis overall being Kaposi’s
sarcoma (12/31 [39%]). There were 5/31 (16%) cases of nonHodgkin’s lymphoma. The most common non-AIDs defining
cancer was basal cell carcinoma of which there were 5/31
(16%) cases, followed by squamous cell carcinoma (3/31
[10%]) and testicular cancer (3/31 [10%]). Other cancers
included colorectal (2/31 [6%]) and prostate cancer (1/31
[3%]). In all five deceased patients, cancer was the cause of
death. There were four acute presentations with an aggressive glioma, Burkitt’s lymphoma, an undiagnosed primary
lung malignancy and a late diagnosed cervical cancer. The
fifth patient died following the recurrence of a transitional
cell cancer of the bladder after an initial diagnosis of seven
years earlier. Eighteen out of sixty-nine (26%) of females
were found to have at least mild dyskariosis on cervical
screening. Anal intraepithelial neoplasia was diagnosed in 4/
438 (1%) of patients.
Conclusions: Non-AIDS defining malignancies account for
almost half of the cancers in our cohort. This number may
rise further as patients live longer with HIV. Good communication between oncologists and HIV physicians is paramount to manage the complex interactions of HIV and
cancer, increase HIV testing in cancer services and address
cancer risk factors in existing HIV patients.
P120
Prevalence and predictors of malignancies in a polycentric
cohort of HIV patients from Italy
Elena Mazzotta1; Monica Tontodonati1; Chiara Gabrielli2;
Susanna Mazzocato3; Marcello Mazzetti4; Katia Falasca5;
Giovanni Cenderello6; Jacopo Vecchiet5; Francesco Barchiesi3;
Daniela Francisci2 and Giustino Parruti1
1
Infectious Diseases Unit, Pescara General Hospital, Pescara, Italy.
2
Infectious Diseases Clinic, Università degli Studi di Perugia, Perugia,
Italy. 3Infectious Diseases Clinic, Department of Biomedical Science,
Poster Abstracts
Università Politecnica delle Marche, Ancona, Italy. 4Infectious
Diseases Unit, AOU Carreggi, Firenze, Italy. 5Infectious Diseases Clinic,
Università ‘‘G. D’Annunzio’’, Chieti, Italy. 6Infectious Diseases Unit,
Galliera Hospital, Genova, Italy.
Introduction: HIV infected patients have a higher risk of
developing cancer than the general population. Kaposi’s
sarcoma, non-Hodgkin’s lymphoma, primary CNS lymphoma
and invasive cervical cancers are considered as AIDS defining
[1]. An increased incidence in recent years has been reported
also for other malignancies after the introduction of cART [2,3].
Materials and Methods: We performed a retrospective
multicentric evaluation of all HIV infected patients with
both AIDS and non-AIDS defining neoplasms at six Infectious
Disease Units spread throughout Italy since 1991 through
2013. Cases were compared with equal number of controls
without neoplasia followed at the same institutions, matched
for length of HIV infection.
Results: Since 1991, 339 consecutive cases of malignancy
were collected from the six convening centres, including
approximately an equal proportion of AIDS (51.2%) and nonAIDS defining tumours. Mean prevalence of tumours among
centres was 8.3% (r. 6.1%9.6%). Mean age at tumour
diagnosis was significantly lower than in controls (42.69
11.0 vs 46.8910.6 years, respectively, pB0.0001). As to risk
factors for HIV infection, approximately 1/4 (26.1%) of
patients were drug abusers, in equal proportion as in controls.
A remarkable higher proportion of cancer patients had CD4 Tcell counts B200 c/mmc at time of diagnosis (45.2% vs
13.3%, pB0.0001). Seventy percent of tumours occurred in
males; 52.8% of tumour patients were diagnosed with AIDS
before and 19.0% at the time of tumour diagnosis. Ninety
(28.1%) tumour patients were dead at the time of data
collection, a much higher proportion than among cases
(12.9%, pB0.0001). Deaths among non-AIDS (20.8%) and
AIDS defining tumour patients (35.0%) were significantly
different (p 0.005). Predictors of AIDS defining tumours at
the time of data collection were: male sex (57.9% vs 40.6%,
p0.004), CD4 T-cell counts B200 c/mmc (63.6% vs 44.1%,
pB0.0001), whereas being cART treated at the time of
tumour diagnosis was protective (38.0% vs 68.0%, pB0.0001).
In the final multivariate model of logistic regression, male sex
(OR 2.0, p0.03) and not being cART treated (OR 2.5,
p0.001) held as independent predictors.
Conclusions: Our retrospection revealed a considerably
high proportion of non-AIDS defining tumours, apparently
at rise in recent years. We registered high prevalence of
tumours in each centre. Absence of cART seemed related
with AIDS defining tumours: once more prevention of late
presentation appeared the way to avoid worse prognosis in
this setting.
References
1. Centers for Disease Control and Prevention. 1993 revised
classification system for HIV infection and expanded surveillance
case definition for AIDS among adolescents and adults. MMWR,
1992.
2. Engels EA, Pfeiffer RM, Goedert JJ, Virgo P, McNeel TS, Scoppa
SM, et al. Trends in cancer risk among people with AIDS in the
United States 19802002. AIDS. 2006;20(12):164554.
105
Poster Abstracts
3. Silverberg MJ, Chao C, Leyden WA, et al. HIV infection and the risk
of cancers with and without a known infectious cause. AIDS.
2009;23(17):233745.
Italy. 6Division of Infectious Diseases, University of Brescia, Brescia,
Italy. 7Clinical Department, National Institute for Infectious Diseases,
Rome, Italy. 8Health Sciences, San Paolo Hospital, University of
Milano, Milano, Italy. 9Nadir Foundation Onlus, Rome, Italy.
Introduction: Sexually transmitted diseases (STDs) data
collected in HIV patients could be used as indicator of
risky sexual behaviour possibly linked to HIV transmission.
We described the STDs incidence over time and identified
higher incidence factors.
Methodology: All patients in the ICONA Foundation Study
enrolled after 1998 were included. STDs considered: anystage syphilis, human papilloma virus (HPV) diseases, gonococcal and non-gonococcal urethritis, herpes simplex virus
(HSV) genital ulcers, vaginitis and acute hepatitis B virus
(HBV), hepatitis A virus (HAV), and hepatitis C virus (HCV)
infections (only for non-IVDU (intravenous drug user) patients).
STDs incidence rate (IR): number of STDs divided by person
years of follow-up (PYFU). Calendar periods: 19982002,
20032007 and 20082012. Predictors of STDs occurrence
were identified using Poisson regression and sandwich
estimates for the standard errors were used for multiple
STD events.
H I V - R E L AT E D I N F E C T I O N S , C O INFECTIONS AND CANCERS, ETC OTHER
P121
Increased incidence of sexually transmitted diseases in the
recent years: data from the ICONA cohort
Antonella Cingolani1; Stefano Zona2; Enrico Girardi3; Alessandro Cozzi
Lepri4; Laura Monno5; Eugenia Quiros Roldan6; Giovanni Guaraldi2;
Andrea Antinori7; Antonella d’Arminio Monforte8 and
Simone Marcotullio9 on behalf of ICONA Foundation Study
1
Division of Infectious Diseases, Department of Public Health,
Catholic University, Rome, Italy. 2Division of Infectious Diseases,
University of Modena and Reggio Emilia, Modena, Italy. 3Department
of Epidemiology, National Institute for Infectious Diseases, Rome,
Italy. 4Infection Population Health, University College London,
London, UK. 5Division of Infectious Diseases, University of Bari, Bari,
Abstract P121Figure 1. Predictors of acquiring STD at multivariable Poisson regression analysis.
106
Poster Abstracts
Results: Data of 9,168 patients were analyzed (median age
37.3 (SD 9.3), 74% male, 30% MSM). Over 46,736 PYFU,
996 episodes of STDs were observed (crude IR 17.3/1,000
PYFU). Median (IQR) CD4/mmc and HIV-RNA/mL at STD: 433
(251600) and 10,900 (20063,000). Highest crude IRs were
observed for any-stage syphilis (3.95, 95% CI 3.594.35),
HPV diseases (1.96, 1.712.24) and acute hepatitis (1.72,
1.491.99). At multivariable analysis (variables of adjustment
shown in Figure 1), age (IRR 0.82 per 10 years younger, 95%
CI 0.770.89), MSM contacts (IRR 3.03, 95% CI 2.523.64 vs
heterosexual) and calendar period (IRR 1.67, 95% CI 1.42
1.96, comparing 20082012 with 19982002) significantly
increased the risk of acquiring STDs. Moreover, having a HIVRNA 50 c/mL (IRR 1.44, 95% CI 1.191.74 vs HIV-RNA B50
c/mL) and current CD4 cell count B100/mmc (IRR 4.66,
95% CI 3.695.89, pB0.001 vs CD4 cell count 500)
showed an increased risk of STDs. Being on ARV treatment
significantly reduced the risk of developing an STD (IRR 0.37,
95% CI 0.320.43) compared to ART-naı̈ve people, even in
the situation of temporary interruption of treatment (IRR
0.51, 95% CI 0.390.43) (see Figure 1).
Conclusions: The overall incidence of STDs has been increasing in the recent years. Interventions to prevent STDs and
potential further spread of HIV infection should target the
recently HIV diagnosed, the young population and MSM.
Being on ARV treatment (potentially an indicator of whether
a person is regularly seen for care) seems to reduce the risk
of acquiring STDs independently of its viro-immunological
effect.
P122
Predictors of lack of serological response to syphilis
treatment in HIV-infected subjects
Vincenzo Spagnuolo; Andrea Poli; Laura Galli; Massimo Cernuschi;
Silvia Nozza; Myriam Maillard; Nicola Gianotti; Hamid Hasson;
Simona Bossolasco; Adriano Lazzarin and Antonella Castagna
Department of Infectious Diseases, IRCCS San Raffaele Hospital,
Milan, Italy.
Introduction: The aim of this study was to determine factors
associated with lack of serological response (LSR) to treatment of syphilis among HIV-infected subjects.
Materials and Methods: Retrospective, longitudinal study on
HIV-infected subjects diagnosed and treated for syphilis and
with an assessable serological response between 1 January
2004 and 15 September 2013. LSR was defined as a B4-fold
decline of rapid plasma reagin (RPR) titer or a failed reversion
to nonreactive (if RPR 51:4 at diagnosis) after one year since
treatment. Diagnoses of syphilis were staged in early syphilis
(primary, secondary and early latent) or late syphilis (tertiary
and late latent) according to clinical examination and
patient’s history. Syphilis was classified in new infections
[NI: positive RPR and TPHA (Treponema pallidum Haemagglutination assay) titers in subjects without previous history
of syphilis] or re-infections [ReI: a ]4-fold increase of RPR
titer in subjects previously successfully treated for syphilis].
Syphilis treatment was prescribed according to CDC guidelines. The crude incidence rates (IRs) of LSR were calculated
per 1000-person months of follow-up (PMFU) as the total
number of LSR episodes divided by the cumulative time
contributed by all subjects (interval time since each syphilis
diagnosis and the date of ascertainment of response). Results
are described as median (IQR) or frequency (%).
Results: 565 diagnoses of syphilis with an assessable serological response in 421 patients; 458 (81%) were early syphilis,
189 (33%) were NI, 376 (67%) were ReI. At first, diagnosis of
syphilis median age was 41 (3647) years, 419 (99.5%) males,
391 (93%) MSM, HIV-infected since 7.7 (3.512.9) years, 75
(18%) HCV or HBV co-infected, 56 (13%) with a previous AIDS
diagnosis, 82 (19%) antiretroviral treatment naı̈ve, 102 (24%)
with HIV-RNA ]50 cp/mL, CD4 576 (437749) cells/
mm3, nadir CD4 308 (194406) cells/mm3. LSRs were
observed in 70/565 (12.4%) treated syphilis. Incidence of LSR
decreased over time [20042008 IR 25.1 (17.233.1)/
1000 PMFU; 20092010 IR 21.1 (12.329.9)/1000 PMFU;
Abstract P122Table 1. Univariate and multivariate Cox proportional hazard model for recurrent events on the risk of lack of
serological response to treatment of syphilis
Multivariate analysisa
Univariate analysis
Characteristics
HR
95% CI
p
HR
95% CI
p
Ageb (per five years older)
1.168
1.0831.260
B0.001
1.101
1.0091.201
0.031
Years since HIV infection diagnosisb (per one-year increase)
1.029
1.0041.054
0.021
1.007
0.9581.058
0.793
Years of antiretroviral treatmentb (per one-year increase)
1.016
0.9951.037
0.134
1.011
0.9541.072
0.703
AIDS diagnosis (yes vs no)
1.398
0.9232.117
0.114
1.078
0.7021.656
0.732
Nadir CD4 (per 100 cells/mL higher)
0.800
0.7130.897
B0.001
0.841
0.7420.953
0.007
CD4 b (5350 vs 350-cells/mL)
HIV-RNAb ( ]50 vs B 50 copies/mL)
0.940
1.236
0.4921.796
0.9231.855
0.852
0.186
1.773
1.1432.750
0.011
HCV or HBV co-infection (yes vs no)
1.304
0.8711.953
0.197
0.978
0.6581.455
0.913
Syphilis stage (late vs early)
1.867
1.2162.864
0.004
1.962
1.2683.036
0.003
Type of infection (new infection vs re-infection)
0.705
0.4431.125
0.141
0.702
0.4521.091
0.116
a
Only covariates with a p B 0.20 at univariate were included in the multivariate analysis; bcharacteristics at the diagnosis of syphilis.
HR hazard ratio; 95% CI, 95% confidence interval of hazard ratio.
107
Poster Abstracts
20112013 IR 10.6 (5.118.2)/1000 PMFU; Poisson regression: p 0.001]. Results of univariate and multivariate
analysis on the risk of LSR are reported in Table 1.
Conclusions: In HIV-infected subjects we observed 12% of LSR
to treatment of syphilis. LSR was associated with an older
age, late syphilis, lower nadir CD4 and detectable HIV viral
load.
Homosexual
1.14
0.81
1.59
0.459
Material and Methods: Retrospective, cross-sectional analysis of neurocognitive profile in HIV-infected cART-treated
patients. All patients underwent neuropsychological (NP)
assessment by standardized battery of 14 tests on 5 different
domains. People were classified as having NCI if they scored
1 standard deviation (SD) below the normal mean in
at least two tests, or 2 SD below in one test. Linear and
logistic regression analyses were fitted using as outcome
Npz8 and impaired/not impaired respectively.
Results: A total of 660 HIV-infected cART-treated individuals
from 2009 to 2014, contributing a total of 1003 tests (mean
age 49 (IQR 4356), male 82%; median current CD4 586/mm3;
18% HCV infected; HIV-RNA B40 cp/mL in 84%). Current ARV
regimen was 2NRTIs1NNRTI 50.3%, 2NRTI1PI/r in 32.6%,
NRTI sparing in 11.1%. Mean CPE of current regimens was 6.6
(95% CI 6.56.7). As per test multivariable analysis, higher
CPE values were associated to poor NP tasks (Beta 0,09;
95% CI 0,14 0,03; p0.002 at multivariable linear regression). The association between higher CPE and increased
NCI risk was confirmed at multivariable logistic regression,
with a 1.24-fold risk of NCI occurrence for each point increase
of CPE of current regimen at the time of NP testing (see Table 1).
In a sensitivity analysis performed only on patients at the first
NP test, the association between higher CPE and poor NP
tasks and enhanced NCI risk was only marginally confirmed
(Beta 0,05; [0,120,02]; p0,19; OR 1,13 [0,95
1,34]; p0.17). Older age, longer time from HIV diagnosis,
current CD4 count B350 cell/mm3 and lower education level
were all associated to an increased risk of NCI.
Conclusions: In our analysis, higher CPE rank is associated to
poorly performing at NP tasking. Even if selection bias could
not be excluded due to retrospective cross-sectional design,
these results fitted with the direct correlation between high
CPE and HIV dementia recently recorded in a large observational database. We think that CPE use to guide ART in
patients neurocognitively impaired should be revised.
IVDU
Other/unknown
0.94
0.93
0.51
0.44
1.74
1.95
0.855
0.841
P123
Central nervous system penetration-effectiveness rank does
not reliably predict neurocognitive impairment in HIVinfected individuals
Raffaella Libertone; Patrizia Lorenzini; Pietro Balestra;
Carmela Pinnetti; Martina Ricottini; Maria Maddalena Plazzi;
Samanta Menichetti; Mauro Zaccarelli; Emanuele Nicastri;
Rita Bellagamba; Adriana Ammassari and Andrea Antinori
Lazzaro Spallanzani IRCCS, Rome, Italy.
Introduction: Central nervous system (CNS) penetrationeffectiveness (CPE) rank was proposed in 2008 as an estimate
of penetration of ARV regimen into the CNS, and validated as
predictor of CSF HIV-1 replication. Results on predictive role of
CPE on neurocognitive and clinical outcome were conflicting.
Abstract P123Table 1. Multivariable analysis of predictors of
neurocognitive impairment by logistic regression model
Multivariable logistic regression
OR
95%
CI
p
Age (per 10 years incr.)
1.04
1.02
1.05
0.000
Mode of HIV transmission
Heterosexual
1.00
Previous aids event
1.72
0.77
3.84
0.186
Years from HIV test (per one year incr.)
1.04
1.02
1.07
0.000
HIV-RNA B40 cp/mL at NPA
0.70
0.45
1.07
0.102
CD4 at NPA, cell/mmc
500
1.00
350500
2.20
1.42
3.42
0.000
1.57
0.83
1.07
0.80
2.30
0.87
0.021
0.000
B 350
Education (per one year more)
HCV co-infection
Negative
1.00
Positive
1.29
0.82
2.03
0.269
Unknown
1.48
0.76
2.88
0.254
Type of current regimen
NRTI NNRTI
1.00
NRTI PIB
NRTI II
1.30
1.70
0.92
0.53
1.85
5.41
0.135
0.369
NTRI sparing
1.09
0.56
2.15
0.792
Other
0.81
0.38
1.76
0.599
CPE 2010
1.23
1.07
1.41
0.003
P124
CNS safety at 48-week of switching to ATV/r plus 3TC or two
nucleos(t)ides in HIV-suppressed patients on stable ART: the
SALT neurocognitive sub-study
Ignacio Pérez Valero1; Juan Pasquau2; Rafael Rubio3; Antonio Ribero4;
Jose Santos5; Jesus Sanz6; Ana Mariño7; Manel Crespo8;
Jose Hernandez9; Jose Antonio Iribarren10; Felix Gutierrez11;
Alberto Terron12; Herminia Esteban13 and Jose Antonio PérezMolina14
1
Internal Medicine, H.U. La Paz, Madrid, Spain. 2Internal Medicine,
Hospital Virgen de las Nieves, Granada, Spain. 3Internal Medicine,
H.U. Doce de Octubre, Madrid, Spain. 4Internal Medicine, Hospital
Reina Sofia, Cordoba, Spain. 5Internal Medicine, Hospital Virgen de la
Victoria, Malaga, Spain. 6Internal Medicine, Hospital de Alcala de
Henares, Alcala de Henares, Spain. 7Internal Medicine, Hospital
Arquitecto Marcide, Ferrol, Spain. 8Internal Medicine, Hospital Vall
d’Hebron, Barcelona, Spain. 9Internal Medicine, Hospital San Cecilio,
Granada, Spain. 10Internal Medicine, Hospital de Donostia, San
Sebastian, Spain. 11Internal Medicine, Hospital de Elche, Elche, Spain.
12
Internal Medicine, Hospital de Jerez, Jerez, Spain. 13Fundación
SEIMC-GESIDA, Madrid, Spain. 14Infectious Diseases, Hospital Ramón
y Cajal, Madrid, Spain.
108
Poster Abstracts
ATV/r 3TC N 76 (48.1%)
Male. N (%)
Age. Mean (SD)
ATV/r 2 NRTI N 82 (51.9%)
p
54 (71.1)
63 (76.8)
0.47
43.1 (10.3)
41.6 (8.6)
0.32
Immigrants (%)
19 (25%)
18 (22%)
0.09
Years of education. Mean (SD)
13.0 (4.7)
13.6 (5.0)
0.48
AIDS. N (%)
24 (31.6)
22 (26.8)
0.60
Years since HIV detection. Mean (SD)
7.5 (6.2)
7.3 (6.4)
0.57
Years with HIV-RNA B 50 c/mL. Mean (SD)
Nadir CD4 (cells/mm3). Median (IQR)
3.1 (2.9)
211 (70325)
3.0 (2.7)
193 (130300)
0.92
0.90
Baseline CD4 (cells/mm3). Median (IQR)
575 (388772)
624 (417825)
0.12
3.8 (3.0)
3.6 (2.3)
0.94
Years of ART. Mean (SD)
Hepatitis C Antibody . N (%)
Aterogenic index (Total CHO/HDL), median (IQR)
16 (21.1)
16 (19.5)
0.85
3.9 (3.34.8)
3.9 (3.34.7)
0.76
0.21
Presence of neurological comorbidities. N (%)
3 (3.9)
8 (9.8)
Presence of psychiatric comorbidities. N (%)
36 (47.4)
42 (51.2)
0.64
Presence of cardiovascular comorbidities. N (%)
45 (59.2)
41 (50)
0.27
Introduction: Due to their low CNS penetrance, there are
concerns about the capacity of non-conventional PI-based
ART (monotherapy and dual therapies) to preserve neurocognitive performance (NP).
Methods: We evaluated the NP change of aviremic participants of the SALT clinical trial [1] switching therapy to dual
therapy (DT: ATV/r3TC) or triple therapy (TT: ATV/r
2NRTI) who agreed to perform an NP assessment (NPZ-5) at
baseline and W48. Neurocognitive impairment and NP were
assessed using AAN-2007 criteria [2] and global deficit scores
(GDS) [3]. Neurocognitive change (GDS change: W48 baseline) and the effect of DT on NP evolution crude and
adjusted by significant confounders were determined using
ANCOVA.
Results: A total of 158 patients were included (Table 1). They
had shorter times because HIV diagnosis, ART initiation and
HIV-suppression and their virologic outcome at W48 by
snapshot was higher (79.1% vs 72.7%; p0.04) compared
to the 128 patients not included in the sub-study. By AAN-2007
criteria, 51 patients in each ART group (68% vs 63%) were
neurocognitively impaired at baseline (p 0.61). Forty-seven
patients were not reassessed at W48: 30 lost of follow-up (16
DT-14 TT) and 17 had non-evaluable data (6 DT-11 TT). Patients
retested were more likely to be men (78.9% vs 61.4%) and had
neurological cofounders (9.6% vs 0%) than patients nonretested. At W48, 3 out of 16 (5.7%) patients on DT and 6 out of
21 (10.5%) on TT who were non-impaired at baseline became
impaired (p 0.49) while 10 out of 37 (18.9%) on DT and 7 out
of 36 (12.3%) on TT who were neurocognitively impaired at
baseline became non-impaired (p 0.44). Mean GDS changes
(95% CI) were: Overall 0.2 (0.3 to 0.04): DT 0.26
( 0.4 to 0.07) and TT 0.08 ( 0.2 to 0.07). NP was
similar between DT and TT (0.15). This absence of differences
was also observed in all cognitive tests. Effect of DT: 0.16
[ 0.38 to 0.06]) (r2 0.16) on NP evolution was similar to TT
(reference), even after adjusting (DT: 0.11 [ 0.33 to 0.1],
TT: reference) by significant confounders (geographical origin,
previous ATV use and CD4 cell count) (r2 0.25).
Conclusions: NP stability was observed after 48 weeks of
follow up in the majority of patients whether DT or TT was
used to maintain HIV-suppression. Incidence rates of NP
impairment or NP impairment recovery were also similar
between DT and TT.
References
1. Perez-Molina JA, Rubio R, Rivero A, Pasquau J, Suárez I, Riera M,
et al. Switching to dual therapy (ATV/RIT3TC) vs Standard triple
therapy (aATV/RITtwo nucleos(t)ides) is safe and effective in
patients on virologically stable antiretroviral therapy: 48-week
primary endpoint results from a randomized clinical trial (SALT
study). 20th IAC. 2025 July 2014. Melbourne (Australia). Abstract
LBPE18.
2. Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M,
et al. Updated research nosology for HIV-associated neurocognitive
disorders. Neurology. 2007;69(18):178999.
3. Carey CL, Woods SP, Rippeth JD, Gonzalez R, Moore DJ, Marcotte
TD, et al. Initial validation of a screening battery for the detection of
HIV-associated cognitive impairment. Clin Neuropsychol. 2004;18(2):
23448.
P125
Ongoing epidemic of lymphogranuloma venereum in HIVpositive men who have sex with men: how symptoms
should guide treatment
Gerrit Mohrmann1; Christian Noah1; Michael Sabranski2; Hany Sahly1
and Hans-Jürgen Stellbrink2
1
Infektionsmedizin, Labor Lademannbogen MVZ GmbH, Hamburg,
Germany. 2Study Center, Infektionsmedizinisches Centrum Hamburg,
Hamburg, Germany.
Introduction: Lymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by chlamydia trachomatis (CT) genotype L (L1, L2 and L3). Recent outbreaks
of LGV in Europe and North America affected mainly men
who have sex with men (MSM). Infections with CT serotypes
D-K are mostly associated with mild symptoms or may be
clinically silent. However, infections with L genotypes are
109
Poster Abstracts
more invasive and induce anogenital ulcer or inguinal
lymphadenopathy.
Materials and Methods: Between 2003 and 2013, anal or
genital CT infections were diagnosed in 471 symptomatic
patients attending the Infectious Diseases Center Hamburg
(ICH). CT DNA was detected by PCR. CT genotyping of positive samples was performed by sequence analyses of omp1
PCR products (samples between 2003 and 2010). Samples
between 2012 and 2013 were analyzed by genotype L
specific real-time PCR.
Results: In total, 221 LGV patients were identified (3 in 2003;
11 in 2004; 26 in 2005; 33 in 2006; 24 in 2007; 16 in 2008; 18
in 2009; 15 in 2010; 17 in 2011; 26 in 2012 and 32 in 2013).
One hundred ninety-eight of 221 (89.6%) patients with LGV
were HIV-infected; 10 of 221 (4.5%) were HIV-negative, and
the HIV-status unknown in 13 (5.9%). The majority of LGV
positive patients (204/221; 92%) had anorectal symptoms
(bloody proctitis, rectal pain, purulent or mucous discharge,
tenesmus, constipation), compared to 17/221 (8%) who
presented with genital symptoms as urethritis, genital ulcer
or inguinal lymphadenopathy. Of 283 CT-positive patients
with anorectal symptoms, genotype L was detected in 205
(72%), while non-L genotypes (D-K) were found in 78 (28%).
In contrast, genotype L was found in only 6% of patients with
genital symptoms (11/177), whereas 94% (166/177) were
infected with non-L genotypes only.
Conclusions: The epidemic of LGV among predominantly
HIV MSM is ongoing. LGV might be underdiagnosed, especially in patients with anorectal symptoms. Infections with
CT serotypes D-K are more often associated with urogenital
symptoms or asymptomatic infection, whereas LGV genotypes
are found most frequently in patients with rectal/intestinal
symptoms. Anorectal CT infections in MSM should be further
characterized by genotyping for LGV, as for LGV three weeks
of doxycycline treatment are recommended. CT genotypes
D-K generally require shorter antibiotic treatment. If CT
genotyping is not available, the duration of treatment should
be prolonged to three weeks empirically for CT-positive
patients with anorectal or intestinal symptoms.
P126
APRI and FIB-4 scores are not associated with
neurocognitive impairment in HIV-infected persons
Raffaella Libertone; Pietro Balestra; Patrizia Lorenzini;
Carmela Pinnetti; Martina Ricottini; Samanta Menichetti;
Maria Maddalena Plazzi; Alberto Giannetti; Valerio Tozzi;
Andrea Antinori and Adriana Ammassari
Clinical Department, National Institute for Infectious Diseases,
Rome, Italy.
Introduction: Chronic liver disease leads to neurocognitive
impairment (NCI) and more advanced liver fibrosis is associated with greater deficits. Further, cognitive performances
do not differ significantly among patients affected by diverse
types of chronic liver diseases. Thus, it would be useful to
have a clinical tool associated with early cognitive change
applicable to the HIV-infected population with high HCV
prevalence. Aim of the analysis was to assess the association
between NCI and aspartate aminotransferase-platelet ratio
index (APRI) or Fibrosis-4, which are non-invasive scores used
to assess liver fibrosis.
Materials and Methods: Single-centre, retrospective, crosssectional analysis of cART-treated HIV-infected patients undergoing neuropsychological assessment (NPA) by a set of 14
standardized and comprehensive tests on five different domains:
concentration and speed of mental processing; mental flexibility; memory, fine motor functioning; visual-spatial and
Association of variables with NCI
Risk of HAND
Univariate analysis
Multivariate analysis -1
HR
95% CI
p
HR
Years of education (each y more)
0.80
0.760.85
B0.01
BMI B18, each point more
2.69
1.245.86
0.01
CDC stage C
2.52
1.653.86
B0.01
1.96
1.153.36
HCV-positivity
2.46
1.673.64
B0.01
1.75
CD4/mmc at nadir (each 100 cells)
CD4/mmc at NPA (each 100 cells)
0.79
0.93
0.700.89
0.870.99
B0.01
0.02
e-GFR at CG B60 mL/min
1.92
1.282.88
Multivariate analysis -2
95% CI
p
HR
95% CI
p
0.81
0.760.87
B0.01
2.19
0.855.66
n.s.
0.81
0.760.87
B0.01
2.08
0.805.40
0.01
1.94
1.143.32
n.s
1.023.00
0.04
1.63
0.952.81
n.s.
0.98
0.94
0.831.16
0.851.04
n.s.
0.19
0.98
0.89
0.831.17
0.771.03
n.s.
n.s
0.002
1.49
0.872.56
n.s.
1.49
0.872.54
n.s.
0.01
FIB-4 score
Min/1.44
1.00
1.453.25
1.75
1.162.64
0.01
0.94
1.00
0.551.60
n.s
3.26-max
3.77
1.718.28
B0.01
1.23
0.443.41
n.s.
Min/1.44
1.453.25
1.00
1.88
1.222.90
B0.01
1.00
1.37
0.792.37
n.s.
3.26-max
2.60
1.145.95
0.02
1.35
0.503.65
n.s.
APRI score
110
Poster Abstracts
constructional abilities. NPA obtained from the same patient
were included, if collected while receiving different cART.
Patients were classified as having NCI, if they scored 1 SD
below the normative mean in at least two tests, or below 2
SD in one test. HIV-associated neurocognitive disorders
(HAND) were classified according to Frascati’s criteria, controlling for confounding comorbidities. Univariable analysis and
multivariable logistic regression models were carried out.
Results: A total of 556 HIV-infected cART-treated patients from
2006 to 2013 were included: male 78%; IVDUs 14%; CDC stage
C 31%; median CD4 nadir 200/mm3; median current CD4 501/
mm3; undetectable HIV-RNA in 368 (67%); and HCV-positivity
in 150 (29%). Frequency among score levels was for FIB-4:
min-1.44 404 (73%), 1.453.25118 (21%), 3.26-max 28
(5%); for APRI: min-0.5 414 (75%), 0.51.5 112 (20%), 1.5max 24 (4%). Median FIB-4 and APRI were 0.98 and 0.27 in
HIV/HCV- and 1.40 and 0.50 in HIV/HCV individuals,
respectively. HAND was found in 176 (32%): 91 ANI, 73 MND,
12 HAD. Association of variables with NCI are shown in Table 1.
Conclusions: In this large population, HAND was not associated with commonly used non-invasive liver fibrosis scores.
As aetiology of cognitive dysfunction in HIV mono- and HCV
co-infected patients is multifactorial and partially unknown,
our results support the hypothesis of a direct or indirect effect
on cognitive function of the viruses, rather than the consequence of alterations residing outside the brain.
P127
Low clinical relevance of risky alcohol consumption in a
selected group of high adherent HIV-infected patients
attended in the United Kingdom
Alicia Gonzalez Baeza1; Ana Milinkovic2 and Alejandro Arenas-Pinto2
1
Centre of Sexual Health and HIV Research, University College
London Medical School, London, UK. 2Centre for Sexual Health &
HIV Research, Mortimer Market Centre, off Capper Street
London, UK.
Introduction: The prevalence of risky alcohol consumption,
associated factors and its impact on the brain is not well
established in clinically stable HIV patients.
Materials and Methods: Within the PIVOT neurocognitive
sub-study, effectively suppressed HIV-infected adults on
either standard cART or ritonavir-boosted PI monotherapy
completed the Alcohol Use Disorders Identification Test
(AUDIT) designed to detect risky alcohol consumption. They
also completed a brief neuropsychological assessment (NPZ 5)
composed by five measures. For this cross-sectional analysis,
we calculated rates of hazardous (AUDIT 815) or harmful (AUDIT1619) consumption and likely dependence
(AUDIT 20). We explored the association between risky
alcohol intakes (AUDIT8) and clinical/demographical variables, conducting logistic regressions when significant association was found (p B.05). Also, the association between
cognitive performance and alcohol consumption was calculated and adjusted by potential confounders.
Results: Of the 146 included participants, the majority were
male (86.3%), white (81.5%) and educated (mean years
on formal education 15, SD 3.9). Average age was 47.6
years (SD8.7), and 36.3% had risky consumption (29.5%
hazardous, 6.2% harmful, 0.7% likely dependence). White
ethnicity and male sex were positively associated with risky
consumption (Table 1). After adjustments, white ethnicity
remained significantly associated with risky consumption
(1.64 [95% CI 0.342.95]; p0.013). Better cognitive
performance was associated with risky alcohol consumption
in the univariate analysis (p B.001). After adjustment by
ethnicity, sex and years of education, cognitive performance
and risky alcohol consumption maintained significant association (0.45 [95% CI 0.190.70] p 0.001).
Conclusions: Despite the substantially high prevalence of risky
alcohol consumption, it was not associated with worse adherence, immunological or quality of life measures in this
cohort of effectively suppressed patients but prevalence of
likely alcohol dependency was extremely low. White patients
Association between clinical and demographical variables and risky alcohol consumption
Coef.
Ethnicity
Std.Err.
z
p
95% Conf. interval
1.757
0.639
2.75
0.006
0.5033.011
Sex
1.811
0.767
2.36
0.018
3.3150.308
Age
0.006
0.200
0.35
0.730
0.4610.032
Years of education
Recreational drug use
0.001
0.436
0.03
0.979
0.0860.084
In the past
0.820
0.442
1.86
0.063
0.0451.687
Currently
0.573
0.468
1.23
0.220
0.3431.490
CD4 cell count
0.000
0.001
0.67
0.501
0.0010.002
1.063
1.109
0.96
0.338
3.2381.110
Moderately
0.115
0.383
0.30
0.762
0.8660.634
Extremely
Physical health summary score
1.166
0.175
1.117
0.197
1.04
0.98
0.297
0.329
3.3551.024
0.5270.018
Viral load
Anxiety/depression perception
Mental health summary score
Self-reported adherence
0.005
0.018
0.28
0.779
0.0340.041
0.165
0.499
0.33
0.741
1.1430.813
111
were more vulnerable to risky consumption. Moreover,
positive association between cognitive performance and risky
alcohol consumption remained after adjustment. In our study,
the association we found between cognitive function and
alcohol consumption does not reflect the effect of alcohol
dependency on cognition.
P128
Predictors of emphysema progression in HIV-positive
patients
Giovanni Guaraldi1; Antonella Santoro1; Giulia Besutti2;
Riccardo Scaglioni2; Guido Ligabue2; Stefano Zona1; Paul Man3;
Don Sin3; Jonathon Leipsic4 and Cristina Mussini1
1
Infectious Disease, Policlinic Hospital, University of Modena and
Reggio Emilia, Modena, Italy. 2Radiology, Policlinic Hospital,
University of Modena and Reggio Emilia, Modena, Italy. 3Respiratory
Medicine, Saint Paul Hospital, British Columbia University, Vancouver,
Canada. 4Radiology, Saint Paul Hospital, British Columbia University,
Vancouver, Canada.
Introduction: The aim of the study was to find factors
associated with emphysema progression (EP), assessed on
sequential thoracic CT scans, in a large cohort of HIV-positive
patients.
Materials and Methods: This was an observational, prospective study of 448 consecutive HIV-positive patients on
antiretroviral therapy who underwent two sequential ECGgated coronary artery calcium scoring CT scans. Images were
reviewed by three radiologists by consensus to assess lung
emphysema using a visual semi-quantitative score (0 to 4) for
each of six lobes. EP was defined as an increase in emphysema
score. Heavy smoking habit was defined as a self-reported
number of cigarettes per day smoked greater than 10.
Immune reconstitution was defined as the change in CD4
cell count between first CT scan and CD4 nadir and it was
divided into tertiles. Progressors and non-progressors were
compared using X2-test for categorical variables and T-test of
MannWhitney U test for continuous variables where appropriate. Factors independently associated with EP were
explored using multivariable logistic regression analyses. A
p-value B.05 was considered statistically significant.
Results: The mean age of the included patients was 47,997,7
years, 24,1% of them were females and 39,3% were smokers.
The median interval between the two CT scans was 2,4 years
(interquartile range 0,695,9 years). EP was significantly
associated with HIV-infection duration (p 0,056), smoking
(p 0,007) and in particular heavy smoking habit (p 0,015)
and time interval between the two scans (p 0,021), while
the highest tertile of immune reconstitution was borderline in
significance (p 0,075). Age and sex were not significantly
related to EP and were not included in further analyses. HIV
infection duration (OR 1,01; p 0,013), time interval between the two scans (OR 1,51; p0,032) and heavy
smoking habit (OR 3,36; p0,041) remained independently associated with EP in multivariate analysis.
Conclusions: In this large cohort of HIV positive patients on
antiretroviral therapy, HIV infection duration, time between
CT scans and continued heavy cigarette smoking were
independently associated with EP.
Poster Abstracts
References
1. Petrache I, Diab K, Knox KS, Twigg HL, Stephens RS, Flores S, et al.
HIV associated pulmonary emphysema: a review of the literature and
inquiry into its mechanism. Thorax. 2008;63(5):4639.
2. Diaz PT, Clanton TL, Pacht ER. Emphysema-like pulmonary disease
associated with human immunodeficiency virus infection. Ann Intern
Med. 1992;116:1248.
3. Sampériz G, Guerrero D, López M, Valera JL, Iglesias A, Rı́os A,
et al. Prevalence of and risk factors for pulmonary abnormalities in
HIV-infected patients treated with antiretroviral therapy. HIV Med.
2014;15(6):3219.
4. Laurence J. HIV and the lung in the HAART era. AIDS Read.
2005;15(7):327, 330.
5. Diaz PT, King ER, Wewers MD, Gadek JE, Neal D, Drake J, et al. HIV
infection increases susceptibility to smoking-induced emphysema.
Chest. 2000;117(5 Suppl1):285S.
P129
Should screening for Chlamydia trachomatis and Neisseria
gonorrhoeae in HIV-men who have sex with men be
recommended?
Isabel Pérez-Hernández1; Rosario Palacios1; Carmen GonzálezDoménech1; Victoria Garcı́a2; Manuel Márquez1; Encarnación Clavijo2
and Jesús Santos1
1
Infectious Diseases Unit, Hospital Virgen de la Victoria, Málaga,
Spain. 2Microbiology, Hospital Virgen de la Victoria, Málaga, Spain.
Introduction: Sexually transmitted infections (STI) like
Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG)
have been associated with increased risk of HIV acquisition
[1]. It has been also described as a high prevalence of asymptomatic CT and NG infections in men who have sex with men
(MSM) [2]. The aim of this study was to know the prevalence
of CT and/or NG infections in asymptomatic HIV-MSM and the
related factors.
Material and Methods: Prospective study of a cohort of
asymptomatic HIV-MSM with follow-up in Malaga (southern
Spain) during October 2012May 2014. Patients with an
opportunistic event or who received active antibiotic therapy
for CT and/or NG in the previous month were excluded. All of
them completed a questionnaire about sexual behaviour,
barrier methods and recreational drugs use. Demographical,
epidemiological, clinical, analytical and therapeutic data were
also collected. Pharyngeal and rectal swabs, and urine
samples were collected to be tested for CT and NG by nucleic
acid amplification test (c4800 CT/NG. Roche Diagnostics,
Mannheim, Germany) [3]. Statistics analysis: SPSS 17.0.
Results: 255 patients were asked to participate and 248 of
them accepted. Median age was 37.7 (30.646.3) years,
median time since HIV diagnosis was 47.7 (10.5104.1)
months, and median CD4 cells count was 607 (440824)
cell/mL. There were 195 (78.6%) patients on antiretroviral
therapy; 81.5% of them had undetectable viral load. 80.5% of
the patients had a past history of STI. Infection by CT and/or
NG was diagnosed in 24 (9.7%) patients. Overall four urine
samples, two pharyngeal, and 15 rectal ones were positive for
CT, and five pharyngeal and five rectal swabs were positive for
NG. Two patients were co-infected by CT and NG: one with CT
in urine and both in rectum, another with CT in urine and
112
rectum and NG in pharynx. One patient presented CT in
pharynx and rectum, and two patients NG in pharynx and
rectum. Positive CT and/or NG tests were only related with
detectable HIV viral load (OR 3.08, 95% CI 1.27.4; p0.01).
It was not related with sexual behaviour, nor with alcohol or
recreational drugs use.
Conclusions: STI screening had a great acceptance in this
population. There was a high prevalence of asymptomatic CT
and/or NG infections. Rectum sample was the most effective
one. Viral suppression could protect from these STI. Screening should be recommended in HIV-MSM.
References
1. Bernstein K, Marcus J, Nieri G, Philip SS, Klausner JD. Rectal
gonorrhea and chlamydia reinfection is associated with increased risk
of HIV seroconversion. AIDS. 2010;53:53743.
2. Benn PD, Rooney G, Carder C, Brown M, Stevenson SR, Copas A,
et al. Chlamydia trachomatis and Neisseria gonorrhoeae infection
and the sexual behaviour of men who have sex with men. Sex
Transm Infect. 2007;83:10612.
3. Rockett R, Goire N, Limnios A, Turra M, Higgens G, Lambert SB, et al.
Evaluation of the cobas 4800 CT/NG test for detecting Chlamydia trachomatis and Neisseria gonorrhoeae. Sex Transm Infect. 2010;86:4703.
Poster Abstracts
HPV types (80.5% vs 56.0%, pB.001), was significantly
higher among HIV-infected than HIV-uninfected individuals.
HPV-multiple infections were evidenced in 48.2% of the HIVuninfected and 76.1% of the HIV-infected MSM (p B.001).
HPV16 was the most prevalent genotype in both groups
(23.3% in HIV-positive and 17.6% in HIV-negative MSM).
HPV6 and 84 were the most frequent low-risk types in both
cohorts. Anal cytologic abnormalities were found in a
significantly higher proportion of HIV-infected MSM (46.1%
vs 27.9%, pB.001). H-SILs (high-grade squamous intraepithelial lesions) were exclusively observed among the HIVinfected individuals, although at a low prevalence (1.2%).
Conclusions: A high prevalence of anal HPV infection and
cytologic abnormalities was evidenced in both populations.
Nonetheless, HIV-infected MSM showed a significantly higher
rate of HPV infection and abnormal cytology, confirming that
HIV-1 infection poses a significant risk for anal HPV infection
as well as for anal cellular abnormalities. Screening for anal
cancer, which is currently the most frequent non-AIDSdefining cancer in HIV-positive MSM, should be considered
for this population. Moreover, vaccination strategies for the
prevention of HPV infection should be taken into account.
P130
P131
Prevalence of anal human papillomavirus infection and
cytologic abnormalities among HIV-infected and HIVuninfected men who have sex with men
Alessandra Latini1; Maria Gabriella Dona1; Livia Ronchetti2;
Amalia Giglio3; Domenico Moretto3; Manuela Colagli1;
Valentina Laquintana2; Mirko Frasca1; Mauro Zaccarelli4;
Andrea Antinori4; Antonio Cristaudo1 and Massimo Giuliani1
1
Infectious Dermatology and Allergology Unit, San Gallicano
Dermatologic Institute, IRCCS, Rome, Italy. 2Pathology Department,
Regina Elena National Cancer Institute, IRCCS, Rome, Italy. 3Clinical
Pathology and Microbiology DepartmentSan Gallicano Dermatologic
Institute, IRCCS, Rome, Italy. 4Clinical Department, National Institute
for Infectious Diseases ‘‘Lazzaro Spallanzani’’, Rome, Italy.
Introduction: Human papillomavirus (HPV) is responsible for
85% of anal cancers. Recently, anal cancer incidence has been
increasing, particularly in men who have sex with men
(MSM). Cytology may be a useful tool for the detection of
anal precancerous lesions. We assessed the prevalence and
determinants of anal HPV infection and cytologic abnormalities among HIV-infected and -uninfected MSM.
Materials and Methods: MSM ]18-year-old attending an STI
clinic in Rome (Italy) were enrolled. Anal cytologic samples
were collected in PreservCyt (Hologic) using a Dacron swab.
The Linear Array HPV Genotyping Test (Roche Diagnostics)
was used for the detection and genotyping of 37 mucosal HPV
types. Liquid-based cytological slides were obtained using a
ThinPrep2000 processor (Hologic). The morphology of the
anal pap-test was classified following the Bethesda 2001
guidelines.
Results: We enrolled 180 HIV-infected (median age 41 years,
IQR 3347) and 438 HIV-uninfected MSM (median age 32
years, IQR: 2739). Most of the individuals were Caucasian
(92.2% and 97.0%, respectively). HPV prevalence, both
overall (93.3% vs 72.4%, pB.001) and by high-risk (HR)
More safer sex intervention needed for HIV-positive MSM
with higher education level for prevention of sexually
transmitted hepatitis C
Ada Wai Chi Lin; Ka Hing Wong and Kenny Chan
Special Preventive Programme, Department of Health, Kowloon,
Hong Kong, China.
Introduction: The epidemiology of hepatitis C virus (HCV)
infections in Chinese HIV-infected men who have sex with
men (MSM) remains obscure. More data is required to
understand the epidemic and set up preventive strategy.
Materials and Methods: Baseline and annual testing of antiHCV was in place for all HIV-infected MSM in the largest HIV
clinic in Hong Kong. Logistic regression was used to compare
those with HCV seroconversion (seroconverters) with those
remained tested anti-HCV negative (non-seroconverters) to
identify factors associated with incident HCV.
Results: From 1999 to 2013, 1311 patients were tested for
anti-HCV seroconversion, contributing to 6295 patient-years
of observation. Fourteen (1.1%) patients seroconverted, with
genotype 3 being most commonly detected. The overall
incidence rate of HCV infection was 0.22 per 100 patientyears (PY) in the cohort. The incidence rate increased from
0.13 per 100PY before 2002 to 0.19 per 100PY in 20022007
and 0.47 per 100PY in 20082013. All the seroconverters
were Chinese, with median age of anti-HCV seroconversion at
38 years (range: 2853 years). None of them were injecting
drug users. As compared with the non-seroconverters,
seroconverters were of higher education level (85.7% vs
50.7% tertiary education or above, OR 5.28, p0.021) and
had prior history of sexually transmitted infection (92.9% vs
60.9%, OR 8.34, p0.041). More seroconverters were found
to have history of syphilis infection (57.1% vs 37.2%,
p0.134) but the difference was not statistically significant.
113
Poster Abstracts
Abstract P131Table 1. Comparison between HCV seroconverters and HCV non-seroconverters
HCV seroconverters (n 14) HCV non-seroconverters (n 1297)
Median age (years)
Ethnicity
Education level
Chinese
Non-Chinese
No school or below
38
14 (100%)
0
2 (14.3%)
40
1126 (86.8%)
171 (13.2%)
639 (49.3%)
secondary school
Tertiary school or
12 (85.7%)
658 (50.7%)
p
0.556
0.996
0.021
above
Baseline median CD4 count (ml3)
Baseline median HIV viral load (cp/mL3)
On antiretroviral therapy
Median duration of antiretroviral
therapy (days)
Prior history of sexually transmitted
261
935,000
9 (64%)
317
330
55,000
833 (64.2%)
479
0.331
0.509
0.996
0.962
13 (92.9%)
790 (60.9%)
0.041
infection
Prior history of syphilis
8 (57.1%)
482 (37.2%)
0.134
Baseline CD4 count and HIV viral load, proportion on
antiretroviral therapy and duration of antiretroviral therapy
were not different between two groups.
Conclusions: The incidence of HCV has been increasing
among HIV-infected MSM non-injecting drug users in Hong
Kong. More education and intervention on safer sex is
required to be targeted on those with higher education level.
P132
Facial emotional processing deficits in long-term HIVsuppressed patients
Alicia Gonzalez-Baeza1; Ignacio Perez-Valero1; Fernando CarvajalMolina2; Carmen Bayon3; Marisa Montes-Ramirez1; Jose Ignacio
Bernardino1 and Jose R Arribas1
1
HIV Unit, IdiPAZ Hospital Universitario La Paz, Madrid, Spain.
2
Psicologia Biologica y de la Salud, Universidad Autonoma de Madrid,
Madrid, Spain. 3Psiquiatria, IdiPAZ Hospital Universitario La Paz,
Madrid, Spain.
Introduction: Emotional processing is basic for social behaviour. We examine for the first time the facial emotion
processing in long-term HIV-suppressed patients.
Materials and Methods: Cross-sectional study comparing
(ANOVA) six facial emotional processing tasks (two discrimination, two memory and two recognition) between HIVsuppressed patients (HIV) on effective antiretroviral therapy
( 2 years) and matched (age, gender) healthy controls
(HCs). Accuracy in the recognition of basic emotions (neutral,
happiness, sadness, anger and fear) in each recognition task
was also compared (MannWhitney U test) between HIV
and HCs. In the subset of HIV, we evaluate which factors
were associated with impaired recognition of basic emotions
(accuracy below 50%) by multiple logistic regression analysis.
Overall performance in all six emotional tasks were separately compared between neurocognitive impaired and nonimpaired HIV.
Results: We included 107 HIV, mainly Caucasian (89%)
male (72%) with a mean age of 47.4 years, neurocognitively
non-impaired (75.5%), and 40 HCs. Overall discrimination
(p 0.38), memory (p 0.65) and recognition tasks
(p 0.29) were similar in both groups. However, HIV had
lower sadness recognition in both recognition tasks and
lower sadness, anger and fear recognition in the facial affect
selection task (Figure 1). Only estimated pre-morbid functioning (WAIS-III-R vocabulary subtest score) was significantly
Abstract P132Figure 1. Percentage of correct recognition responses given in each specific emotion by HIV and healthy control participants.
Note: Significant differences (pB.05) in distribution of correct response calculated by Mann-Whitney U-test. Axis Y% of correct response.
114
Poster Abstracts
associated with sadness (1.99 [95% CI 1.183.58]; p0.01)
and anger recognition deficits (2.06 [95% CI 1.143.45];
p0.015) in the facial affect selection task. In HIV
individuals, neurocognitive impairment was associated with
worse memory task results (p B0.01, d 0.88; pB0.01,
d1.48).
Conclusions: We did not find difference in the overall
emotion processing between HIV and HIV- individuals.
However, we found particular recognition deficits in the
entire HIV sample. Estimated pre-morbid functioning was
associated with sadness and anger recognition deficits in the
facial affect selection task. Neurocognitive impaired HIV
had additional memory deficits. These recognition deficits
might conduct to social difficulties.
Reference
P133
Co-infections and co-morbidities among injecting drug users
versus sexually infected patients in Bucharest
Eliza Manea1; Raluca Jipa1; Iulia Niculescu2; Serban Benea2;
Otilia Benea2; Victoria Arama2 and Adriana Hristea2
1
INBI Prof Dr Matei Bals, Bucharest, Romania. 2INBI Prof Dr Matei
Bals, Umf Carol Davila Bucharest, Bucharest, Romania.
Introduction: After the 2008 introduction of new psychoactive substances (NPS) in Romania, the number of newly
diagnosed HIV infections showed significant increase among
injecting drug users (IDUs). Our objective was to analyze the
differences between co-infections related to the HIV infection, based on the way of transmission (IDUs versus sexually
infected).
Material and Methods: A retrospective transversal study was
carried out, analyzing 245 adult HIV-positive patients,
diagnosed between January 2013 and December 2013 in
our hospital. We collected socio-demographic, epidemiological and laboratory data at the diagnosis and analyzed them
using SPSS version 20.
Results: Most patients (71%, 174/245) were men and the
median age was 32 years (IQR: 2638). 91 patients (37%)
were former/active IDUs (most of them injecting both
opioids and NPS), while 154 patients (63%) were sexually
infected, with 84% being heterosexuals and 16% men having
sex with men (MSM). The median CD4 count, at the moment
of diagnosis, was 294 cells/mm3 (IQR: 119483).
Other co-infections at diagnosis were toxoplasmosis (four
patients), cryptococcosis (two patients) and cytomegalovirus
reactivations (three patients) without significant association
between the two groups.
Conclusion: Heterosexual transmission was the most common
way of HIV transmission in 2013 in contrast with EU/CEE,
where MSM accounted for the majority of cases of HIV
epidemics in 2012 [1]. Sexually transmitted HIV infection
was associated with late presentation, stage C and syphilis.
We noted a high percentage of IDU transmission, which was
associated with stage A and hepatitis C infection.
1. 2012 HIV/AIDS surveillance in Europe European Centre for
Disease Prevention and Control, Stockholm, WHO Regional Office for
Europe, Copenhagen.
LABORATORY MONITORING OF DISEASE
AND THERAPY GENERAL
P134
Clinical and socio-demographic predictors for virologic
failure in rural Southern Africa: preliminary findings from
CART-1
Niklaus Daniel Labhardt1; Joëlle Bader2; Mojakisane Ramoeletsi3;
Mashaete Kamele4; Thabo Ismael Lejone4; Molisana Cheleboi5;
Mokete M. Motlatsi4; Jochen Ehmer6; Olatunbosun Faturyiele4;
Daniel Puga7 and Thomas Klimkait2
1
Department of Medical and Diagnostic Services, Swiss Tropical and
Public Health Institute, Basel, Switzerland. 2Department Biomedicine,
University of Basel, Basel, Switzerland. 3Laboratory Services, Paray
Hospital, Thaba-Tseka, Lesotho. 4SolidarMed, SolidarMed Lesotho,
Patient characteristics
IDUs (N 91)
Male N (%)
Sexually infected (N 154)
p value, OR (95% CI)
0.015, 0.4 (0.20.8)
73 (80)
101 (66)
30 (IQR: 2634)
34 (IQR: 2641)
B0.001
350 (IQR: 154600)
272 (IQR: 91405)
B0.001
Late presenters (CD4 B 350) N (%)
45 (50)
102 (66)
0.01, 1.3 (1.01.7)
Stage A N (%)
60 (66)
60 (39)
B0.001, 3.0 (1.75.2)
Stage B N (%)
Stage C N (%)
21 (23)
10 (11)
53 (34)
41 (27)
0.062, 0.5 (0.31.03)
0.004, 2.4 (1.24.6)
Hepatitis C N (%)
84 (92)
8 (5)
B0.001, 255.5 (85.7761.4)
Hepatitis B N (%)
12 (13)
19 (12)
0.822, 1.09 (0.52.3)
Syphilis N (%)
4 (4)
26 (17)
0.006, 3.6 (1.310.0)
Tuberculosis N (%)
1 (1)
13 (8)
0.064, 0.1 (0.071.3)
Pneumocystosis N (%)
2 (2)
7 (5)
0.709, 0.7 (0.14.2)
Age (years) (median, IQR)
CD4 (cells/mm3) (median, IQR)
IQR interquartile range, IDUs injecting drug users.
115
Thaba-Tseka, Lesotho. 5Laboratory Services, Seboche Hospital, BothaBothe, Lesotho. 6SolidarMed, SolidarMed Switzerland, Lucerne,
Switzerland. 7SolidarMed, SolidarMed Lesotho, Botha-Bothe, Lesotho.
Introduction: In 2013, the World Health Organization (WHO)
recommended scaling up of routine viral load (VL) monitoring
for patients on antiretroviral therapy (ART) in resourcelimited settings [1]. During the transition phase from no VLtesting at all to routine VL-monitoring, targeted VL for groups
at particular risk of virologic failure (VF) may be an option [2].
We present socio-demographic and clinical risk factors for VF
in a cohort in rural Lesotho with no access to VL prior to the
study.
Materials and Methods: Data derive from a cross-sectional
study providing multi-disease screening as well as VL testing
to adult patients ( ]16 years old) on first-line ART ]6
months [3]. VF was defined as VL]1000 copies/mL. Assessed
potential predictors of VF were: (1) socio-demographic (sex,
age, wealth-quintile, education, employment status, disclosure of HIV status to environment, travel-time to facility); (2)
treatment history (history of treatment interruption 2 days,
previous drug substitution within first-line ART, time on ART,
ART-base and -backbone); (3) adherence (pill count) and (4)
clinical (clinical or immunological failure as defined by WHO
guidelines [1], presence of papular pruritic eruption (PPE)).
All variables with association to VF in univariate analysis
were included in a multivariate logistic regression reporting
adjusted Odds ratios (aOR).
Results: Data from 1,488 patients were analyzed. Overall VFprevalence was 6.9% (95% CI 5.78.3). In univariate analysis,
the following were associated with VF: age B30, lower
wealth-quintile, no primary education, history of treatment
interruption, nevirapine-base, zidovudine-backbone, history
of drug substitution, travel-time to clinic ]2 hours, disclosure
of HIV status to B5 persons, clinical failure, presence of PPE
and immunological failure. In multivariate analysis, 6 out
of the above 12 variables were independent predictors: age
B30 years (aOR: 2.4; 95% CI 1.15.3, p0.029), history of
treatment interruption (2.5; 1.34.7, p0.005), PPE (6.9;
2.518.9, pB0.001), immunological failure (11.5; 5.723.2,
pB0.001), history of drug substitution (1.9; 1.03.7, p
0.043), disclosure of HIV status to B5 persons (1.8; 1.13.1,
p0.03).
Conclusion: In this cohort in rural Lesotho, several sociodemographic and clinical predictors were associated with VF.
Particularly age B30 years, history of treatment interruption,
PPE and immunological failure were strongly associated with
VF. These patients may be prioritized for targeted VL-testing.
References
1. World Health Organization. Consolidated guidelines on the use of
antiretroviral drugs for treating and preventing HIV infection. 2013;
Available from: http://www.who.int.
2. World Health Organization. Supplementary section to the 2013
WHO consolidated guidelines on the use of antiretroviral drugs for
treating and preventing HIV infection, Chapter 7*Antiretroviral
therapy. 2014; Available from: http://www.who.int.
3. Comorbidities and virologic outcome among patients on antiretroviral therapy in rural Lesotho (CART-1 Study). Available from:
http://www.clinicaltrials.gov; Identifier: NCT02126696.
Poster Abstracts
P135
Difference in factors associated with low-level viraemia and
virological failure: results from the Austrian HIV Cohort
Study
Gisela Leierer1; Armin Rieger2; Andrea Steuer3; Mario Sarcletti1;
Maria Geit4; Bernhard Haas5; Ninon Taylor6; Manfred Kanatschnig7;
Michaela Rappold1; Bruno Ledergerber8 and Robert Zangerle1
1
Department of Dermatology and Venereology, Innsbruck Medical
University, Innsbruck, Austria. 2Department of Dermatology, Medical
University Vienna, Vienna, Austria. 3Department of Pulmonary
Medicine, Otto Wagner Hospital, Vienna, Austria. 4Department of
Dermatology, Allgemeines Krankenhaus Linz, Linz, Austria.
5
Department of Infectious Diseases, Landeskrankenhaus Graz West,
Graz, Austria. 6Department of Internal Medicine III, Paracelsus
Medical University Salzburg, Salzburg, Austria. 7Department of
Internal Medicine, Landeskrankenhaus Klagenfurt, Klagenfurt,
Austria. 8Division of Infectious Diseases, University Hospital Zurich,
Zurich, Austria.
Introduction: For some patients, it remains a challenge to
achieve complete virological suppression which is the goal of
antiretroviral therapy (ART). Identifying factors associated
with low-level viraemia (LLV) and virological failure (VF)
under ART might help to optimize management of these
patients.
Materials and Methods: We investigated patients from the
Austrian HIV Cohort Study receiving unmodified ART for 6
months with two nucleoside reverse-transcriptase inhibitors
(NRTIs) with either a non-nucleoside reverse-transcriptase
inhibitor (NNRTI) or a boosted protease inhibitor (PI) or an
integrase inhibitor (INSTI) between 1 July 2012 and 1 July
2013 with at least one viral load (VL) measurement below the
limit of detection (BLD) or below level of quantification (BLQ)
in their treatment history. VF was defined as HIV-RNA levels
]200 copies/mL and all other quantifiable measurements
were classified as LLV. Factors associated with LLV and VF
compared to BLD and BLQ were identified by using logistic
regression models.
Results: Of the 2,276 patients analyzed, 1,972 (86.6%) were
BLD or BLQ, 222 (9.8%) showed LLV and 82 (3.6%) had VF. A
higher risk for LLV and VF was found in patients with ART
interruptions and in patients with boosted PI therapy. The
risk for LLV and VF was lower in patients from a centre which
uses Abbott RealTime HIV-1 assay compared to the other
centres measuring VL by the Roche Cobas AmpliPrep/Cobas
TaqMan 2.0. A higher risk for LLV but not for VF was found in
patients with a higher VL before ART and shorter ART
duration. A higher risk for VF but not for LLV was found in
patients of younger age, originating from a high prevalence
country, with a lower CD4 count and in male injecting drug
users.
Conclusions: This study of well-defined patients on stable
ART over a period of more than six months gives insights into
the different factors associated with LLV and VF. In patients
with VF, factors associated with adherence play a prominent
role, whereas in patients with LLV, the biology of viral
replication comes additionally into effect. Despite its observational design, it has implications for patient management and forms the basis for future outcome studies.
116
Poster Abstracts
Abstract P135Table 1. Multivariable logistic regression results: Association between different factors and low-level
viraemia and virological failure compared to viral load below
the limit of detection or below level of quantification
LLVB200
VF]200
OR (95% CI)
OR (95% CI)
Joana Silva1; Karen Pereira1; Joao Rijo2; Teresa Alberto1;
Joaquim Cabanas3; Perpetua Gomes3; Helena Farinha2 and
Kamal Mansinho1
1
Infectious Diseases, Hospital Egas Moniz CHLO, E.P.E., Lisboa,
Portugal. 2Pharmaceutical Department, Hospital Egas Moniz CHLO,
E.P.E., Lisboa, Portugal. 3Microbiology and Molecular Biology
Laboratory, Hospital Egas Moniz CHLO, E.P.E., Lisboa, Portugal.
B 9 months
918 months
2.50 (1.334.72) 0.72 (0.163.24)
0.99 (0.571.71) 1.24 (0.552.79)
Introduction: Low-level viraemia (LLV) is observed in some
patients with HIV-1 infection on stable antiretroviral therapy
(ART). The significance of these findings remains controversial as it conflicts with traditional optimal clinic outcome. This
study aims to evaluate the effect of LLV on the establishment
of virological failure (VF) and immune deterioration.
Methods: Retrospective observational study of a cohort of
HIV-1 infected patients of an Infectious Diseases Clinic, who
presented an HIV-1 viral load of 20 to 200 cp/mL, during the
year 2012. Patients who were not on ART or non-adherent in
the previous 6 months were excluded. Compliance was
quantified by clinical and pharmaceutical records. Adherence
was defined as ]95% compliance rate. Demographic, clinical,
immunological and therapeutic data were collected from
clinical records. LLV was defined as a range of 20200 cp/mL
and stratified as transient (T-LLV): only one measurement,
persistent (P-LLV): 2 consecutive measurements with an
interval ]3 months and recurrent (R-LLV): ]1 T-LLV during
an 18-month follow-up. Statistical analysis was performed
with Microsoft Office† Excel 2012. KolmogorovSmirnov
test, t-test and chi-square test were performed for a significant
p value B0.05.
Results: During 2012, 2161 HIV-1 infected patients were
evaluated at our Clinic, 93% of which were on ART. LLV was
documented in 378 (19%), adherence was verified in 151
(52%). The analysis of this cohort (n 151) revealed: 77
(51%) T-LLV, 13 (8.6%) R-LLV and 61 (40%) P-LLV. Mean viral
load was 46 cp/mL. Mean TCD4 count was 665 cells/mL with a
variation of 63 cells/mL during the study period. There was
no VF documented. ART regimens were switched in 16 (11%)
patients. Gastrointestinal disturbance was found in 13 (9%).
Analysis showed no statistical differences between the
analyzed variables (CD4 variation, time of diagnosis and
treatment, duration of LLV persistence (less than or more
than one year), number of ART regimens, ART regimen and
type of NRTI backbone) for all groups (T-LLV, R-LLV, P-LLV),
except for mean viral load that showed significant superiority
in the T-LLV(38 cp/mL) and R-LLV(36 cp/mL) vs P-LLV(58 cp/mL)
(p 0.01 and pB0.01, respectively).
Conclusions: The absence of significant differences in immunological and virological outcomes in this cohort and the
absence of VF in all groups, suggests a scarce impact of LLV in
patient’s prognosis. Prospective studies, with longer followup could bring more accurate information.
18 months
1.00 (Reference) 1.00 (Reference)
Outcome
Age at VL measurement
B 30 years
1.01 (0.581.76) 2.95 (1.078.18)
3050 years
0.98 (0.701.36) 2.80 (1.286.10)
50 years
Male injecting drug user
1.07 (0.661.73) 2.04 (1.004.18)
Female injecting drug user
Male heterosexual
0.42 (0.161.08) 1.44 (0.484.28)
0.85 (0.581.25) 0.69 (0.311.54)
Female heterosexual
0.62 (0.410.94) 1.11 (0.552.24)
Other
1.36 (0.722.58) 1.27 (0.354.61)
Men who have sex with
men
Nationality
High prevalence countries
2.14 (1.044.41)
Low prevalence countries
CD4 count at VL measurement
1.00 (Reference)
Missing
2.12 (1.074.19) 0.65 (0.085.08)
B 200 cells/mL
1.70 (0.863.36) 9.17 (4.1820.13)
200349 cells/mL
0.98 (0.621.57) 2.81 (1.485.32)
350499 cells/mL
0.94 (0.621.41) 2.53 (1.384.65)
] 500 cells/mL
Ever ART interruptions
]1
None
1.80 (1.332.43) 2.49 (1.534.05)
Assay used
Abbott RealTime (single
0.34 (0.210.53) 0.11 (0.030.35)
centre)
Roche TaqMan 2.0
(6 centres)
ART regimen
2 NRTI PI/r
2 NRTI NNRTI/INSTI
1.53 (1.142.05) 2.35 (1.433.86)
VL before ART
Missing
2.12 (1.034.37) 1.14 (0.423.07)
99.999 copies/mL
3.66 (1.927.00) 1.32 (0.592.98)
9.99999.999 copies/mL
2.17 (1.114.22) 1.99 (0.904.41)
5 9.999 copies/mL
ART duration
P136
A retrospective observational study of low-level viraemia
and its immunological and virological significance: which
outcome to expect
P137
Longitudinal comparison of HIV-1 plasma viral load and
cellular proviral load
Finja Schweitzer1; Visa Mikkola1; Monika Timmen-Wego1;
Björn Jensen2; Gerd Fätkenheuer3 and Rolf Kaiser1
117
Poster Abstracts
1
1
2
2
Institute of Virology, University of Köln, Köln, Germany.
Department of Gastroenterology and Hepatology, University
Hospital Düsseldorf, Düsseldorf, Germany. 3Department of Internal
Medicine, University Hospital Köln, Köln, Germany.
Introduction: The goal of antiretroviral treatment (ART) in
HIV-1 infection is the permanent suppression of plasma viral
load (pVL) below the currently existing limit of detection
of 50 copies/mL (DAIG HIV-therapy guidelines). Therefore,
treatment effectiveness is based on pVL. pVL measurements
however do not give any information about the viral
reservoir in peripheral blood mononuclear cells (PBMCs).
Therefore, the proviral DNA of HIV-1 could be a useful marker
for the investigation of viral reservoirs and monitoring ART in
patients showing undetectable pVL.
Materials and Methods: Seventy-seven treatment-experienced HIV-1 infected patients with pVL B50 copies/mL
were randomly selected. pVL and proviral DNA load were
measured using the Roche COBAS TaqMan HIV-1 v2.0 assay.
Additionally, CD4 cell count per mL and the total white
blood cell (wbc) count per mL were determined for each
patient. Follow-up data were collected 24 weeks after the
time point of the first measurement. Proviral DNA load per
mL, CD4 cell count per mL as well as wbc count per mL were
observed over time and differences were estimated using the
MannWhitney U test. Additionally, correlations between the
clinical parameters were analyzed using the two-sided
Pearson correlation analysis.
Results: Out of the 77 patients, 38 show a significant
increase in proviral load per mL over time (p 0,001),
whereas 39 patients show a significant decrease (p 0,001).
No differences became visible in the CD4 cell count
per mL comparing week 0 and week 24 data. Thirty five
patients show a significant increase in wbc count per mL
over time (pB0,001), while 42 patients show a significant
decrease (p B0,001). A significant correlation of increasing proviral load per mL and wbc count per mL for data
of the first (p B0.001) and the second measurement
(p B0.001) can be detected, while there are no correlations
found between proviral load per mL and CD4 cell count
per mL.
Conclusions: Our data show that the presence of viral
reservoirs in other cell types and not only CD4 cells is
most probable. HIV-1 proviral DNA seems to be an interesting
marker in patients with undetectable pVL and allows the
assessment of replication under ART. Nevertheless, further
longitudinal studies are needed to assess the usefulness and
the clinical significance of this marker.
P138
Analysis of transmitted drug resistance and HIV-1 subtypes
using dried serum spots of recently HIV-infected individuals
in 2013 in Germany
Hauser Andrea1; Hofmann Alexandra2; Santos-Hoevener Claudia2;
Zimmermann Ruth2; Hamouda Osamah2; Bannert Norbert1 and
Kuecherer Claudia1
HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany.
HIV/AIDS and Other Blood Borne Infections, Robert Koch Institute,
Berlin, Germany.
Introduction: The Robert Koch Institute (RKI) aimed to assess
a molecular surveillance strategy based on filter-dried serum
spots (DSS) of all newly diagnosed HIV infections in Germany.
In 2013, diagnostic laboratories sent DSS to the RKI representing 55% of the newly diagnosed HIV infections reported
to the RKI (protection against infection act). DSS were first
tested serologically to identify recently acquired infections
( B140 days duration of infection); those classified as ‘‘recent
infection’’ were processed for HIV-1 genotyping. The aim of
this study was to assess the level of TDR and the current HIV-1
subtypes in the main HIV transmission group categories
(TrGrpC) in 2013: men who have sex with men (MSM),
women/men with heterosexual contacts (HET) and injecting
drug users (IDUs).
Material and Methods: DSS were tested for recency of
infection using the BED capture EIA. Viral RNA from ‘‘recent
infections’’ was amplified by HIV-1 group M generic pol-RTPCR covering all resistance-associated positions in the HIV-1
protease (AS1-99) and reverse transcriptase (AS1-252) if viral
loads were ]6,500 copies/mL. PCR amplicons were sequenced (Sanger) to analyze genotypic resistance and the
HIV-1 subtype. Results were merged to data from the HIV
report, i.e. the TrGrpC.
Results: In 2013, 1027 DSS were classified as recent HIV
infections (506 MSM, 118 HET, 31 IDUs, 6 others, 366
unknown). RNA was extracted from 703 recent cases and
389/503 samples with sufficient viral load were PCR-positive.
By June 2014, 276/389 samples were sequenced: TDR was
identified in 13% (35/276) of the recent infections including
single (PI, NRTI, NNRTI) and dual drug class resistant strains
(NRTI/NNRTI; NNRTI/PI). 18% (51/276) of recent HIV-1
infections were caused by non-B subtypes (A1, C, CRF01_AE,
CRF02_AG, D, F, G, URFs). TDR was observed at comparable
levels in all TrGrpC. Proportions of non-B infections were
significantly higher in HET (78%; 14/18) and IDUs (60%; 3/5)
compared to MSM (8%; 14/169) (p B0.01).
Conclusions: The proportion of TDR was similar but the
proportion of HIV-1 subtype non-B infections was higher as
previously described for Germany based on results from the
German HIV-1 Seroconverter Cohort [1,2]. This difference could be the result of a broadened inclusion of HET and
IDUs due to the sampling method used making this study
representative for molecular surveillance of HIV-1 in Germany.
References
1. Meixenberger K, Scheufele R, Somogyi S, Jansen K, Bartmeyer B,
Dupke S, et al. Pronounced potential of resistance mutations to
persist in transmitted drug resistant HIV-1 strains. 12th European
Workshop on HIV & Hepatitis Treatment Strategies, Spain; 2628
March 2014; Poster P_11.
2. Somogyi S, Meixenberger K, Bartmeyer B, Jansen K, Scheufele R,
Dupke S, et al. Continued rising prevalence of HIV-1 non-B subtypes
in Germany: Update from the HIV 1 Seroconverter Study; 12th
European Workshop on HIV & Hepatitis Treatment Strategies,
Spain; 2628 March 2014; Poster P_18.
118
Poster Abstracts
P139
Reference
Comparison of routine versus targeted HIV testing
strategies: coverage and estimated missed infections in
emergency room and primary care centre
1. Hayes R, Sabapathy K, Fidler S. Universal testing and treatment as
an HIV prevention strategy: research questions and methods. Curr
HIV Res. 2011;9:42945.
Marı́a Jesús Pérez Elı́as1; Cristina Gomez-Ayerbe1; Alfonso Muriel2;
Maria Eugenia Calonge3; Alberto Diaz1; Pilar Pérez Elı́as3;
Maria Martinez-Colubi4; Almudena Uranga3; Cristina Santos3;
Ana Moreno1; Carmen Quereda1; Enrique Navas1 and
Santiago Moreno1
1
Infectious Diseases, Hospital Ramón y Cajal, IRYCIS, Madrid, Spain.
2
Statistics Department, Hospital Ramón y Cajal, IRYCIS, CIBERESP,
Madrid, Spain. 3Family Care, Centro de Salud Garcı́a Noblejas,
Madrid, Spain. 4Internal Medicine, Hospital de Sanchinarro, Madrid,
Spain.
Introduction: Different HIV Testing Strategies (TS) and
clinical care settings had not been face to face evaluated
[1]. We compared coverage, Newly Diagnosed HIV Infection
(NDHI) and Estimated Missing HIV Infections (MHI) in
Hospital Emergency Room (HER) and Primary Care Center
(PCC), in DRIVE study (Spanish acronym of HIV infection
Rapid Diagnosis) and in clinical practice the year before
DRIVE.
Materials and Methods: In DRIVE study, 1860 years old,
non-HIV-infected population visiting an HER or a PCC were
proposed both a structured risk practices and clinical
conditions questionnaire (RP&CC-Q) and a rapid HIV test.
This arm is the HIV Routine TS. We analyze a hypothetical
arm, where risk practices were universally assessed with an
RP&CC-Q, subsequently risk-positive patients where HIV
tested, Targeted-TS. Coverage was assessed as the ratio of
tested population (TP)/attended population (AP) in HER and
PCC. TP/AP ratios were also calculated in the year before,
the Clinical Practice-TS. NDHI was expressed per tests
performed. MHI was estimated assuming in the non-tested
population, overall DRIVE rate of NDHI and NDHI in
negative RP&CC-Q.
Results: A total of 5329 RP&CC-Q and rapid HIV tests
were performed to 49.64% women, median age 37 (2847)
years old, mainly 74.9% Spaniards. Confirmed NDHI was
4.1, and in 48, 8% of RP&CC-Q negative NDH was 0. HIV
screening coverage was always better in PCC than in HER, and
higher in DRIVE study than in clinical practice. Estimated MHI
was higher in HER and in the clinical practice-TS. Targeted-TS
coverage was lower, but resulted in similar NDHI and MHI
than routine-TS, testing half the population, see Table 1.
Conclusions: Best HIV Testing Strategy is routine-TS in
Primary Care Center. Targeted-TS resulted in same newly
HIV diagnoses and missed HIV infections than routine-TS with
half the resources employed.
P140
Relationship between discordant response to HAART, Tregs,
immune activation and low-level viraemia
Julien Saison1; Tristan Ferry1; Julie Demaret2; Delphine MaucortBoulch3; Fabienne Venet2; Thomas Perpoint1; Florence Ader1;
Vinca Icard1; Christian Chidiac1 and Guillaume Monneret4
1
Infectious and Tropical Disease Unit, Hôpital de la Croix-Rousse,
Lyon, France. 2Immunology Laboratory, Hôpital Edouard Herriot,
Lyon, France. 3Biostatistic Unit, Hospices Civils de Lyon, Lyon, France.
4
Immunology Laboratory, Hopital Edouard Herriot, Lyon, France.
Introduction: The incomplete immune recovery upon effective long-term highly active antiretroviral therapy (HAART)
has been associated with increased morbidity and mortality
in HIV infected patients [1]. Immune cellular activation, Tregs
or very low-level viraemia has been alternatively suspected,
but never investigated simultaneously [2].
Materials and Methods: We performed a cross-sectional study
in 87 aviraemic patients (men 62, mean CD4T cells 570/
mm3, mean duration of HAART12 years). Patients with at
least 500 CD4 T cells /mm3 were classified as complete
immunological responders (cIR), whereas remaining patients
were classified as inadequate immunological responder (iIR).
Tregs were characterized based on CD4CD25high
FoxP3phenotype using a one-step intracellular staining.
Effector Tregs and terminal effectors Tregs were respectively
defined as CD4CD25FoxP3CD45RA-, and CD4CD25
FoxP3CD45RA-HLADRphenotypes as recently described
[3]. Activated T cells were identified using (i) elevated HLA-DR
expression for CD4T cells, and (ii) increased expressions of
HLA-DR, or CD38, or both (HLADRCD38cells) for CD8T
cells. Very low-level viraemia was defined as detectable
viraemia between 1 and 39 cp/mL. Univariate and multivariate
analyses were performed to identify determinants of iIR.
Results: Thirty-nine patients were classified as iIR, and 48 as
cIR. Patients from the iIR group were significantly older (55 vs
50 years, p0.027), and had percentages of activated CD4
T cells, Tregs, effector Tregs and terminal effector Tregs
significantly higher (5.3 vs 4%, p0.014; 9 vs 7.5%, p
0,022; 8 vs 6.3%, p0.01 and 1.8 vs 1.3%, p0,033 among
CD4T cells, respectively). Neither the percentage of activated CD8T cell nor very low-level viraemia were found to
Abstract P139Table 1. Coverage, newly diagnosed HIV infections, missed HIV infections
Settings
Hospital emergency room
Hospital emergency room
Primary Care Center
Primary Care Center
Coverage
0.31
NDI/no MHI
0/139
Coverage
3.7
NDI/no MHI
2.4/23
DRIVE routine 2012/2013
2.6
8.6/128
32.9
2.2/16
DRIVE targeted 2012/2013
1.43
8.6/128
16.25
2.2/16
Testing strategies
Clinical practice 2011/2012
119
be associated with iIR. In the multivariate analysis, nadir of
CD4T cell count and percentage of Tregs were the only two
parameters independently associated with iIR (OR 2.339,
p0.001, and OR0.803, p 0.041, respectively).
Conclusion: We present here the largest study investigating
simultaneously immune response to long-term HAART, immune activation of CD4 and CD8 T cells, Tregs percentages and very low-level viraemia. Our results highlight the
importance of Tregs in CD4 homeostasis. This aspect should
now be prospectively explored in a large cohort of patients.
References
1. Rodger AJ, Lodwick R, Schechter M, Deeks S, Amin J, Gilson R,
et al. Mortality in well controlled HIV in the continuous antiretroviral
therapy arms of the SMART and ESPRIT trials compared with the
general population. AIDS. 2013;27:9739.
2. Gaardbo JC, Hartling HJ, Gerstoft J, Nielsen SD. Incomplete
immune recovery in HIV infection: mechanisms, relevance for clinical
care, and possible solutions. Clin Dev Immunol. 2012;2012:670957.
3. Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3
regulatory T cells in the human immune system. Nat Rev Immunol.
2010;10:490500.
P141
Everything fine so far? Physical and mental health in HIVinfected patients with virological success and long-term
exposure to antiretroviral therapy
Gesa Erdbeer1; Michael Sabranski2; Ina Sonntag1; Albrecht Stoehr3;
Heinz-A. Horst1; Andreas Plettenberg3; Knud Schewe2; Stefan Unger3;
Hans-J. Stellbrink2; Stefan Fenske2 and Christian Hoffmann2
1
University of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
2
Infektionsmedizinisches Centrum Hamburg, Study Center, Hamburg,
Germany. 3IFI, Institute for Interdisciplinary Medicine, Hamburg,
Germany.
Introduction: Little is known about the well-being on longterm exposure to antiretroviral therapy. The ACTG Augmented Symptoms Distress Module (ASDM) is a validated tool
which measures the presence of a total of 22 symptoms seen
with HIV and quantifies the extent to which they cause
distress to the patient.
Methods: ELBE was a cross-sectional study that consecutively
included adult HIV-infected patients presenting with viral
suppression ( B50 HIV RNA copies/mL) and ART exposure for
at least five years. Patients were evaluated by four different
questionnaires, including ASDM.
Results: Of a total of 894 patients included in the three
participating ELBE centres, complete data on ASDM were
available for 698 patients (626 male, 69 female, 3 transsexual).
Median age was 49.7 years (range, 23.382.5 years) and median
exposure to ART was 11.5 years (range, 528 years). Median
CD4 T-cell counts had increased from a CD4 nadir of 180 to
currently 640 cells/mL. Despite immunological and virological
success, a high degree of symptom-related distress was noted
in this patient population. In total, 63.8% and 36.3% of the
patients had at least one ‘‘bothersome’’ or one ‘‘very bothersome’’ symptom, respectively. The symptoms most frequently
reported to be ‘‘bothersome’’or ‘‘very bothersome’’ were fatigue
and energy loss (18.5% and 11.0% respectively), insomnia
(12.8% and 11.6%), sadness and depression (13.0% and 10.0%),
sexual dysfunction (12.0% and 10.0%), and changes in body
Poster Abstracts
appearance (11.0% and 10.9%). There was no association
between the degree of symptom-related distress and gender,
age or CD4 T-cell nadir. However, the history of AIDS-defining
illnesses, comorbidities such as depression but also the
duration of ART were significantly associated with a higher
overall symptom summary score and with a higher frequency
of symptoms. For example, in patients with at least 15 years of
ARTexposure, only 27.3% of the patients did not report at least
one ‘‘bothersome’’ or ‘‘very bothersome’’ symptom.
Conclusions: In this large group of positively selected HIV
patients with virological success and long-term exposure to
ART, a high degree of symptom-related distress was found.
Medical care of HIV-infected patients should not only focus
on optimal virological outcome. More data on quality of life
in patients with long-term exposure to ART is needed.
P142
Accurate episomal HIV 2-LTR circles quantification using
optimized DNA isolation and droplet digital PCR
Eva Malatinkova1; Maja Kiselinova1; Pawel Bonczkowski1;
Wim Trypsteen1; Peter Messiaen2; Jolien Vermeire3;
Bruno Verhasselt3; Karen Vervisch1; Linos Vandekerckhove1 and
Ward De Spiegelaere1
1
Department of Internal Medicine, Ghent University and University
Hospital Ghent, Ghent, Belgium. 2Department of Infectious Diseases
and Immunity, Jessa Hospital, Hasselt, Belgium. 3Department of
Clinical Chemistry and Microbiology, Ghent University and University
Hospital Ghent, Ghent, Belgium.
Introduction: In HIV-infected patients on combination
antiretroviral therapy (cART), the detection of episomal HIV
2-LTR circles is a potential marker for ongoing viral replication.
Quantification of 2-LTR circles is based on quantitative PCR or
more recently on digital PCR assessment, but is hampered due
to its low abundance. Sample pre-PCR processing is a critical
step for 2-LTR circles quantification, which has not yet been
sufficiently evaluated in patient derived samples.
Materials and Methods: We compared two sample processing
procedures to more accurately quantify 2-LTR circles using
droplet digital PCR (ddPCR). Episomal HIV 2-LTR circles were
either isolated by genomic DNA isolation or by a modified
plasmid DNA isolation, to separate the small episomal circular
DNA from chromosomal DNA. This was performed in a dilution
series of HIV-infected cells and HIV-1 infected patient derived
samples (n 59). Samples for the plasmid DNA isolation
method were spiked with an internal control plasmid.
Results: Genomic DNA isolation enables robust 2-LTR circles
quantification. However, in the lower ranges of detection, PCR
inhibition caused by high genomic DNA load substantially limits
the amount of sample input and this impacts sensitivity and
accuracy. Moreover, total genomic DNA isolation resulted in a
lower recovery of 2-LTR templates per isolate, further reducing
its sensitivity.The modified plasmid DNA isolation with a spiked
reference for normalization was more accurate in these low
ranges compared to genomic DNA isolation. A linear correlation of both methods was observed in the dilution series
(R20.974) and in the patient derived samples with 2LTR numbers above 10 copies per million peripheral blood
120
mononuclear cells (PBMCs), (R20.671). Furthermore,
BlandAltman analysis revealed an average agreement between the methods within the 27 samples in which 2-LTR circles
were detectable with both methods (bias: 0.387591.2657 log10).
Conclusions: 2-LTR circles quantification in HIV-infected
patients proved to be more accurate with a modified plasmid
DNA isolation procedure compared to total genomic DNA
isolation. This method enables the processing of more blood
cells, thus enhancing quantification accuracy and sensitivity.
An improved quantification of 2-LTR circles will contribute to
the better understanding of ongoing replication in the HIV
reservoir of patients on cART.
P143
Validation of an ultrasensitive digital droplet PCR assay for
HIV-2 plasma RNA quantification
Jean Ruelle; Vasilieios Yfantis; Armelle Duquenne and Patrick Goubau
AIDS Reference Laboratory, Université Catholique de Louvain,
Brussels, Belgium.
Introduction: Low or undetectable plasma viral load (VL) using
current qPCR assays is common for HIV-2 patients. Digital PCR
is an emerging technology enabling more precision and
reproducibility than qPCR at low DNA/RNA copy numbers.
Available data related to digital droplet PCR (ddPCR, Bio-Rad)
underscore issues linked to the threshold definition of
positivity, coupled to the specificity of low copy results [1].
Materials and Methods: A RT-PCR protocol was set up using
the One-Step RT-ddPCR Kit for Probes on the QX200 platform
(Bio-Rad, Hercules, CA) in an accredited environment (ISO15189:
2012 norm). Parameters tested were in line with the digital
MIQE guidelines [2]. Inter-run coefficient of variation (CV) was
established using synthetic RNA controls diluted in HIVnegative plasma. The ddPCR assay was compared to a qRT-PCR
previously used in routine (LOQ 50 cop/mL [3]) using 46 clinical samples and the NIBSC international HIV-2 RNA standard.
Results: The optimal PCR efficiency and the best separation
between positive and negative droplets were obtained with a
mixture containing 0.5 mM manganese acetate, 700 nM
primers and 250 nM of the 5’FAM-probe. Using a manual
threshold to define positivity, 7.74% of negative controls
(n 168) were scored as positive due to one positive droplet.
The presence of two positive droplets or more was not
observed for negative controls. Serial dilutions of a positive
control showed excellent linearity (R2 0.999) and enabled
us to define a limit of quantification of two positives droplets,
which corresponds to 0.14 copies/mL in the reaction mixture
and to seven copies per mL of plasma. The inter-run coefficient
of variation was 3.37% at a mean value of 4,468 cop/mL,
19.59% at 416 cop/mL and 32.28% at 8 cop/mL. The NIBSC
standard of 1,000 IU was quantified 1,400 copies by ddPCR
and close to 5,000 copies by qPCR (delta log superior to 0.5).
Among 46 clinical samples, 22 were undetectable with both
qPCR and ddPCR, 12 were detected with both methods
(respective means of 10,612 and 2,224 cop/mL, delta
log 0.68) and 12 others were quantified by ddPCR only
below 50 cop/mL (mean 16 cop/mL).
Poster Abstracts
Conclusions: We validated a ddPCR HIV-2 VL assay that is
more sensitive and more reproducible than the qPCR assay
used as comparator, with a limit of quantification of 7 cop/
mL of plasma. A careful definition of the limit of blank allows
the management of false positive droplets, but the variable
user-defined positive threshold may be an issue for compliance to the quality norms.
References
1. Strain M, Lada S, Luong T, Rought SE, Gianella S, Terry VH, et al.
Highly precise measurement of HIV DNA by droplet digital PCR. PLos
One. 2013;8(4):e55943.
2. Huggett J, Foy C, Benes V, et al. The digital MIQE guidelines:
minimum information for publication of quantitative digital PCR
experiments. Clin Chem. 2013;59(6):892902.
3. Ruelle J, Kabamba B, Schutten M, Goubau P. Quantitative realtime PCR on Lightcycler for the detection of human immunodeficiency virus type 2 (HIV-2). J Virol Methods. 2004;117(1):6774.
P144
Acute HIV infection (AHI) in a specialized clinical setting:
case-finding, description of virological, epidemiological and
clinical characteristics
Adriana Ammassari1; Isabella Abbate2; Nicoletta Orchi3;
Carmela Pinnetti1; Gabriella Rozera2; Raffaella Libertone1;
Paola Pierro1; Federico Martini4; Vincenzo Puro3; Enrico Girardi3;
Andrea Antinori1 and Maria Rosaria Capobianchi2
1
Clinical Department, National Institute for Infectious Disease, Rome,
Italy. 2Laboratory of Virology, National Institute for Infectious
Disease, Rome, Italy. 3Epidemiology Department, National Institute
for Infectious Disease, Rome, Italy. 4Laboratory of Immunology,
National Institute for Infectious Disease, Rome, Italy.
Introduction: Diagnosis of HIV infection during early stages is
mandatory to catch up with the challenge of limiting HIV viral
replication and reservoirs formation, as well as decreasing
HIV transmissions by immediate cART initiation.
Objectives: Aims were to describe (a) virological characteristics of AHI identified, (b) epidemiological and clinical factors
associated with being diagnosed with AHI.
Methods: Cross-sectional, retrospective study. All individuals
diagnosed with AHI according to Fiebig’s staging between
Jan 2013 and Mar 2014 at the INMI ‘‘L. Spallanzani’’ were
included. Serum samples reactive to a fourth generation HIV1/2 assay (Architect HIV Ag/Ab Combo, Abbott) were retested
with another fourth generation assay (VIDAS DUO HIV Ultra,
Biomérieux) and underwent confirmation with HIV-1 WB
(New Lav I Bio-Rad) and/or with Geenius confirmatory assay
(Bio-Rad). WHO criteria (two env products reactivity) were
used to establish positivity of confirmatory assays. In case of
clinically suspected AHI, HIV-1 RNA (Real time, Abbott) and
p24 assay (VIDAS HIV P24 Bio-Rad) were also performed.
Avidity test was carried out, on confirmed positive samples
lacking p31 reactivity, to discriminate between recent (true
Fiebig V phase) and late infections; to avoid possible misclassifications, clinical data were also used. Demographic,
epidemiological, clinical and laboratory data are routinely,
and anonymously recorded in the SENDIH and SIREA studies.
Results: During the study period, we observed 483 newly HIV
diagnosed individuals, of whom 40 were identified as AHI
121
Poster Abstracts
Abstract P144Table 1. Clinical characteristics and virological exams according to different Fiebig stage
Fiebig classification
Stage II/III (n 7)
Male gender, n (%)
Median age, y (IQR)
Reason for testing, n (%) (missing 4)
- Symptoms
- Periodic testing
- Other
Known HIV sexual partner, n (%)
HIV transmission risk, n (%) (missing 4)
- MSM
- Heterosexual contact
Negative HIV test in past 5 y (missing 11)
Symptomatic AHI, n (%)
Site of testing, n (%)
- Outpatient clinic
- Inpatient
Virological exams
4th gen EIA S/Co ratio, median (IQR)
HIV-1 RNA log copies/mL, median (IQR)
Immunological exams
CD4 /mmc, median (IQR)
13 (100)
33 (3046)
19 (95)
34 (2947)
6 (86)
1914)
0
0
8
4
1
3
(62)
(32)
(7.7)
(23)
7 (35)
12 (60)
1 (5)
1
5
1
3
7
11 (100)
0
7 (88)
11 (85)
16 (84)
3 (16)
11 (65)
10 (50)
5 (71)
2 (29)
10 (100)
0
18 (90)
2 (10)
13.35 (4.1363.10)
7.00 (5.967.00)
40.20 (31.1659.44)
5.71 (4.716.78)
75.72 (42.66249.8)
4.69 (3.715.44)
556 (366696)
535 (397701)
669 (475744)
(83)
(17)
(75)
(100)
Roche VL (copies/mL)
2049
50199
200399
Total
Stage V (n20)
7 (100)
37 (2542)
(8.3%). Fiebig classification showed: 7 stage II/III, 13 stage IV,
20 stage V. Demographic, epidemiological, and clinical
characteristics of patients are shown in the Table. Overall,
the study population had a median S/Co ratio at fourth
generation EIA (Architect) of 49.50 (IQR, 23.5498.05):
values were significantly lower in Fiebig II-IV than in Fiebig V
(38.68 [IQR, 20.0854.84] vs 75.72 [IQR, 42.66249.80],
p0.01). Overall, median HIV-1 RNA was 5.44 log copies/mL
(IQR, 4.296.18) and the value observed in Fiebig phase II-IV
was higher than that found in Fiebig stage V (6.10 [IQR, 5.49
7.00] vs 4.69 [3.715.44], pB0.001). Median CD4 cell
count was 596/mmc (IQR, 410737). cART was started in
26 patients: TDF/FTC/DRV/r/RAL 18; TDF/FTC/DRV/r 2;
TDF/FTC/ATV/r 2; TDFFTCEFV 2; TDF/FTC/RAL1;
DRV/rRAL 1.
Conclusions: Integration of careful epidemiological investigation, partner notification, and technical advances in virological testing are key elements in AHI case-finding. Significant
differences were found between Fiebig stages IIIV and
Fiebig V with regard to virological exams.
Stage IV (n13)
P145
Service impact of a change in HIV-1 viral load quantification
assay
Craig Tipple; Soonita Oomeer; Olamide Dosekun and Nicola Mackie
Jefferiss Wing for Sexual Health, Imperial College Healthcare NHS
Trust, London, UK.
Introduction: Due to discontinuation of the Siemens Versant
HIV-1 RNA (bDNA) assay in the UK, our laboratory switched
to the Roche Cobas Ampliprep/Taqman HIV-1 viral load (VL)
assay (Roche) in April 2013. This assay has a lower cut-off of
20 RNA copies/mL (compared with B50 for the Siemens
assay). Our laboratory demonstrated previously that a
significant proportion (18%) of patients undetectable using
bDNA HIV-1 RNA quantification exhibited low level viraemia
(LLV) using the new assay. Local guidelines recommend that
patients stable on therapy receive twice-yearly VLs. We
evaluated the impact of the introduction of the new assay on
our clinical service.
Methods: A retrospective cohort analysis of treated patients
with stable undetectable VL by bDNA ( B50 copies/mL)
Impact of a change in HIV-1 viral load quantification assay
Total no of VLs requested
No of VLs per patient
No of additional VLs
VC discussion
Genotypes requested
244
201
26
471
2.23
2.83
2.60
n/a
124
134
16
274
8
6
2
16
1
2
3
6
Patients were divided into three groups according to the level of detectable viraemia on the first Roche-measured VL following an undetectable
bDNA result.
122
followed by ] one low-level ( B400 copies/mL) VL with the
Roche assay. Demographic data were collected in addition to
frequency of VL testing and genotypic resistance assays.
Referrals to virtual clinic (VC) were recorded. Patients were
identified using laboratory data and information collected
from electronic patient records. Results were analyzed with
SPSS v18.
Results: One hundred and ninety patients were included.
Demographics: 79.5% male; 60.6% homosexual; mean age of
46 years. Duration on stable treatment was 46.35 (std. dev.
38.15) months. Current treatment regimens were 43.3%
PI-based; 43.3% NNRTI-based and 13.7% other. Patients
were stratified into VL 2049 copies/mL (n 109); VL 50
199 copies/mL (n71) and VL 200399 copies/mL (n 10).
In total, there were 471 VLs measured of which 274 were
additional as a result of the assay switch. This resulted in six
HIV-1 genotype requests and 16 VC discussions (Table 1).
Longer duration on HAART was associated with reduced
frequency of VL testing. The relative risk of ongoing detectability according to drug class are: PI 1.62 (95% CI 1.18
2.21); NNRTI 0.507 (95% CI 0.300.85) and other 1.09 (95%
CI 0.482.43).
Conclusions: Changes in assay can result in difficulties in
interpretation of patient results. The assay switch in our
service had significant impact on patient and staff time and
cost with an increase in patient recalls; increased frequency
of VL measurement, genotypes and discussions in VC. Choice
of assay is paramount to running an efficient and costeffective clinical service.
P146
Outcomes of initial antiretroviral treatment (ART) among
recently diagnosed HIV patients in HIV-TR cohort,
20112012
Volkan Korten1; Deniz Gökengin2; Muzaffer Fincanci3;
Taner Yildirmak4; Nuray Uzun Kes5; Nuriye Taşdelen Fişgin6;
Dilara Inan7; Haluk Eraksoy8; Halis Akalin9 and Figen Kaptan10
1
Infectious Diseases, Marmara University Hospital, Istanbul, Turkey.
2
Infectious Diseases, Ege University Hospital, Izmir, Turkey. 3Infectious
Diseases, Istanbul Education and Research Hospital, Istanbul, Turkey.
4
Infectious Diseases, OkmeydanI Education and Research Hospital,
Istanbul, Turkey. 5Infectious Diseases, Sişli Education and Research
Hospital, Istanbul, Turkey. 6Infectious Diseases, MayIs University
Hospital, Samsun, Turkey. 7Infectious Diseases, Akdeniz University
Hospital, Antalya, Turkey. 8Infectious Diseases, Istanbul Medical
School, Istanbul University, Istanbul, Turkey. 9Infectious Diseases,
Uludağ University Hospital, Bursa, Turkey. 10Infectious Diseases, Izmir
Education Training and Research Hospital, Izmir, Turkey.
Introduction: HIV-TR is a recently established (2012) multicentre cohort in Turkey. The aim of this study is to analyze
epidemiological, immunologic and virologic data of recently
diagnosed HIV patients.
Materials and Methods: Epidemiologic, clinical and laboratory data of all patients diagnosed in 2011 and 2012
were recorded by a web-based data collection system,
retrospectively.
Poster Abstracts
Results: A total of 693 patients (561 male, 132 female) at 24
sites were enrolled. The median age at first presentation for
HIV care was 36. The proportion of patients presenting with
advanced HIV disease (CD4 count B200/mm3 or presenting
with an AIDS-defining event) was 30.6%; and 52.4% of patients
were late presenters (CD4 countB350/mm3 or presenting
with an AIDS-defining event). Median CD4 counts at presentation and before treatment were 344 (IQR: 175540) and
295 (IQR: 150430), respectively. Pretreatment CD4 count
was 500 copies/mL in 18.5% of patients. Of 531 patients
receiving ART, initial combinations consist of tenofovir/
emtricitabine (TDF/FTC) plus efavirenz (EFV) in 48.2% and
TDF/FTC plus lopinavir/ritonavir (LPV/r) in 37.5% and other
combinations in 14.3% of the patients. Pre-treatment HIV-RNA
was over 100.000 copies/mL in 52.3% of patients. At Weeks 24
and 48, HIV-RNA wereB50 copies/mL in 63,4% of 385
patients and 82% of 311 patients reported to be still on ART
and had a viral load measurement, respectively. Median
pretreatment CD4 count was lower for TDF/FTCLPV/r
recipients than TDF/FTCEFV recipients (250 vs 316)
(p B0.05). The median increase from baseline CD4 cell count
was 230 in TDF/FTCLPV/r group, 193 in TDF/FTCEFV group
and 216 among all treated patients. Of 531 patients receiving
ART, 11 had died and 19 were lost to follow-up.
Conclusion: Despite 52.4% of recently diagnosed patients
were late presenters; a high rate of virologic suppression
was achieved in HIV-TR Cohort. A national HIV testing
strategy targeting subpopulations with higher risk is urgently
needed.
P147
Structural-equation-modelling of the tropism impact on
achieving viral suppression within six months in naı̈ve HIV
patients
Carlo Mengoli1; Samantha Andreis1; Renzo Scaggiante1;
Mario Cruciani2; Oliviero Bosco2; Roberto Ferretto3; D. Leone4;
Gaetano Maffongelli4; Monica Basso1; Loredana Sarmati4;
Massimo Andreoni4; Giorgio Palù1 and Saverio Giuseppe Parisi1
1
Department of Molecular Medicine, University of Padova, Padova,
Italy. 2Center of Community & Medicine and HIV Outpatient Clinic,
ULSS 20, Verona, Italy. 3Clinical Infectious Diseases, Schio Hospital,
Schio, Italy. 4Clinical Infectious Diseases, Tor Vergata University,
Rome, Italy.
Introduction: Aim of the study was to evaluate the relevance
of baseline (BL) plasma tropism of HIV on the achievement of
a viral suppression within six months of antiviral therapy
(ARV) in naı̈ve patients by a structural-equation-modelling.
Materials and Methods: Two-hundred and twenty-seven
patients were enrolled; viral tropism on plasma was determined at baseline (BL) by sequencing and interpretation by
genotopheno algorithm. Booster atazanavir or lopinavir , or
efavirenz or nevirapine were used, in combination with either
abacavir/lamivudine or tenofovir-emtricitabine.
Results: X4-tropism correlate negatively with CD4 cell count
at BL and follow-up (FU), and CD4 correlate negatively
with BL-plasma viremia (PLV). BL-PLV correlate positively
123
Poster Abstracts
Abstract P147Figure 1. Path analysis model explaining direct and mediated effects of ‘‘tro’’, ‘‘gender’’, ‘‘age’’, ‘‘cd0’’ and ‘‘lrna0’’ on the
final outcome (lrna1), where tro,gender,and ageare exogenous, cd0 and lrna0 are endogenous (mediators). Numbers on the arrows indicate
direct effects. Circles indicate residuals related to endogenous/dependent variables; numbers near to circles are the corresponding variances.
with FU-PLV. We have developed the hypothesis that the
variables BL-CD4 and BL-PLV represent a mediators chain
among X4-tropism and outcome of plasma viraemia at six
months. This model, after structural-equation-modelling
(SEM, Stata13), is shown in Figure 1. The indirect effect of
X4-tropism on Fup-PLV is significant (pB0.01) but about
10 fold lower than the direct effect by BL-PLV. X4-tropism also
has a direct negative effect on BL-CD4 (p B0.001) and an
indirect positive effect on BL-PLV (p B 0.001), irrespective of
the drug regimen. Path model explaining direct and mediated
effects of ‘‘tro (tropism),’’ ‘‘gender,’’ ‘‘age,’’ ‘‘cd0 (BL-CD4)’’
and ‘‘lrna0 (BL-PLV)’’ on the final outcome (‘‘lrna1-Fup-PLV),’’
where ‘‘tro,’’ ‘‘gender,’’ and ‘‘age’’ are exogenous, cd0 and
lrna0 are endogenous (mediators). Numbers on the arrows
indicate direct effects. Circles indicate residuals related to
endogenous/dependent variables; numbers near to circles are
the corresponding variances.
Conclusions: This model shows the relevance of BL-tropism
on the outcome of plasma viraemia in naı̈ve patients after six
months of therapy, irrespective of drug regimen used.
P148
The absolute lymphocyte count accurately estimates CD4
counts in HIV-infected adults with virologic suppression and
immune reconstitution
Barnaby Young; David Lye; Oon Tek Ng and Yee Sin Leo
Infectious Diseases, Tan Tock Seng Hospital, Singapore.
Introduction: The clinical value of monitoring CD4 counts in
immune reconstituted, virologically suppressed HIV-infected
patients is limited. We investigated if absolute lymphocyte
counts (ALC) from an automated blood counting machine
could accurately estimate CD4 counts.
Materials and Methods: CD4 counts, ALC and HIV viral load
(VL) were extracted from an electronic laboratory database for
all patients in HIV care at the Communicable Diseases Centre,
Tan Tock Seng Hospital, Singapore (200813). Virologic
suppression was defined as consecutive HIV VLs B400 days
apart, B200 copies/mL. CD4 counts and same day ALCs were
collected during virologic suppression from the first CD4 300 cells/mm3. CD4 counts were estimated using the CD4%
from the first value 300 and an ALC 181540 days later.
Results: A total of 1215 periods of virologic suppression
were identified from 1183 patients, with 2227 paired CD4ALCs available for analysis. 98.3% of CD4 estimates were
within 50% of the actual value. 83.3% within 25% and 40.5%
within 10%. The error pattern was approximately symmetrically distributed around a mean of 6.5%, but significant
peaked and with mild positive skew (kurtosis 4.45, skewness
1.07). Causes for these errors were explored. Variability
between lymphocyte counts measured by ALC and flow
cytometry did not follow an apparent pattern, and contributed
to 32% of the total error (median absolute error 5.5%, IQR
2.69.3). The CD4% estimate was significantly lower than the
actual value (t-test, pB0.0001). The magnitude of this
difference was greater for lower values, and above 25%, there
was no significant difference. Precision of the CD4 estimate
was similar as baseline CD4% increased, however accuracy
improved significantly: from a median 16% underestimation to
0% as baseline CD4% increased from 12 to 30. Above a CD4%
baseline of 25, estimates of CD4 were within 25% of the actual
value 90.2% of the time with a median 2% underestimation. A
robust (bisqaure) linear regression model was developed to
correct for the rise in CD4% with time, when baseline was 14
24 (coefficients: intercept 3.30, CD4 0.939). This improved
accuracy from 82.0% to 85.4%, and median error from 11%
underestimation to 1% (p B0.0001). Adding time since baseline CD4% into the model increased complexity without
significantly improving accuracy.
Conclusions: In virologically suppressed hosts with CD4
]300 cells/mm3 and percentage ]14, CD4 counts can be
predicted with 8590% confidence to within 25% of the
actual value using the ALC.
P149
The effect of tenofovir in renal function in HIV-positive
adult patients in the Roma health service area, Lesotho,
southern Africa
Eltony Mugomeri1; Dedré Olivier2 and Elmien van den Heever-Kriek2
124
1
Poster Abstracts
Pharmacy, National University of Lesotho, Maseru, Lesotho. 2Health
Sciences, Central University of Technology, Free State, Bloemfontein,
South Africa.
Hospital Prof. Doutor Fernando Fonseca (HFF), EPE, Amadora,
Portugal.
Introduction: The government of Lesotho introduced tenofovir disoproxil fumarate (TDF) for first-line antiretroviral
treatment (ART), as recommended by the World Health
Organization [1], in 2008. The use of TDF has been associated
with renal toxicity [2]; furthermore, renal function outcomes
following the use of TDF has not been studied at Roma Health
Service Area (RHSA) in Lesotho. Lesotho is a small landlocked
country surrounded by South Africa. The study used an
analytical design to compare retrospective creatinine clearance (CrCl) data of 312 (64%) antiretroviral treatment naı̈ve
adults exposed to TDF and 173 (36%) unexposed patients.
Methods: Impaired renal function was defined as CrCl
less than 50 mL/min calculated using the Cockcroft-Gault
equation. The Ministry of Health and Social Welfare of Lesotho
approved the study on 13 January 2012. The study included
adult (excluding pregnant females) HIV patients enrolled on
ART between December 2006 and December 2012 at St
Joseph’s Mission Hospital and at Nazareth Health Centre
(RHSA). Patients at Nazareth Health Centre and at St Joseph’s
Mission Hospital made up 80% of the circa 4 116 HIV patients
on ART. Only 485 patients met the set inclusion criteria.
Results: In 56 patients (17.9%), TDF was found to be contraindicated. The use of TDF was marginally significant factor for
renal toxicity (p 0.054) in univariate analysis, but was
insignificant (p 0.122) in multivariate logistic analysis. Univariate (p B0.1) and multivariate logistic regression (p B0.05)
were performed using STATA† 11. Female gender (p 0.016),
hypertension (p 0.009), and age 60 (p 0.004) were
significantly associated with CrCl B50 mL/min outcome.
Conclusions: In this study, TDF proofed to be a weak contributing factor of renal impairment. Routine baseline renal
function screening should however be adopted to prevent
patients with impaired renal function receiving TDF.
Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)associated enzyme known as a free radical scavenging system
[1]. PON-1 has three main activities, responsible for its
antioxidant and anti-inflammatory potential: paraoxonase,
arylesterase and lactonase (LACase), the latest to be discovered and pointed out to be its native activity [2].
Among other physiological roles, the LACase might minimize
the deleterious effects of hyperhomocysteinaemia in infection,
by detoxifying the highly reactive metabolite homocysteinethiolactone (HcyTL) [3,4]. In the present work, we have
developed and applied a method to quantify LACase activity
and to explore the role of this enzyme in HIV-infection and
virological response. The LACase activity was monitored in a
cohort of HIV-1-infected patients, through the titration of 3-(ohydroxyphenyl) propionic acid, formed upon the LACasemediated hydrolysis of the substrate dihydrocoumarin. The
study protocol was approved by the Ethics Committee of
Centro Hospitalar de Lisboa Central and Hospital Prof. Doutor
Fernando Fonseca. All patients gave their written informed
consent and were adults with documented HIV-1-infection,
regardless of combined antiretroviral therapy (cART) use. Naı̈ve
patients and patients who had received continuous antiretroviral treatment for more than one month were included. A total
of 179 HIV-1-infected patients were included on this study (51%
Men, 39% non-Caucasian, 45913 years old). Patients with
non-suppressed viraemia, either from the non-cART (n89,
1294 kU/L, pB0.01) or from the cART with detectable viral
load (n 11, 1095 kU/L, p B0.05) groups, had lower activity
than the cART with suppressed viraemia (n 79, 1597 kU/L)
(KruskalWallis test). Among naı̈ve patients, higher viral load
( 31,500 cps/mL, Spearman r 0.535, p0.003) and
lower CD4 T-cells count (B 500 cell/mm3, Pearson r
0.326, p0.024) were associated with the LACase activity. The
present study suggests that lower LACase activity is associated
with uncontrolled HIV-1-infection, particularly with non-suppressed viraemia, despite of cART. This data seems to point to
LACase role in HIV-infection, probably reflecting an increased
formation of HcyTL deleterious species. A better knowledge of
the LACase and its role in HcyTL pathophysiology might identify
new therapeutic targets in HIV-1-infected patients.
References
1. World Health Organisation. Antiretroviral therapy for HIV infection
in adults and adolescents: Recommendations for a public health
approach. Geneva, World Health Organization, 2010. 2010 version
[cited 2013 Oct 20]. Available from: http://whqlibdoc.who.int/
publications/2010/9789241599764_eng.pdf.
2. Young B, Buchacz K, Baker RK, Moorman AC, Wood KC, Chmiel J,
et al. Renal function in tenofovir-exposed and tenofovir-unexposed
patients receiving highly active antiretroviral therapy in the HIV outpatient study. J. Int. Assoc Physicians Aids Care. 2007;6(3):17887.
P150
Monitoring of the lactonase activity of paraoxonase-1
enzyme in HIV-1-infection
Clara Dias1; Aline Marinho1; Judit Morello1; Gabriela Almeida2;
Umbelina Caixas3; Karina Soto4; Emilia Monteiro1 and Soa Pereira1
1
Faculdade de Ciências Médicas, Centro de Estudos de Doenças
Crónicas (CEDOC), Universidade Nova de Lisboa, Pharmacology,
Lisboa, Portugal. 2Departamento de Quı́mica, Instituto Superior de
Ciências de Saúde Egas Moniz, REQUIMTE, CQFB, FCT-UNL, Caparica,
Portugal. 3CEDOC Pharmacology, Centro Hospitalar de Lisboa
Central (CHLC), EPE, Lisboa, Portugal. 4CEDOC Pharmacology,
Acknowledgements: EXPL/DTP-FTO/0204/2012; EXPL/DTPPIC/1758/2013.
References
1. Mackness MI, Arrol S, Abbott C, Durrington PN. Protection of low
density lipoprotein against oxidative modification by high density
lipoprotein associated paraoxonase. Atherosclerosis. 1993;104:
12935.
2. Jakubowski H. Calcium-dependent human serum homocysteine
thiolactone hydrolase. A protective mechanism against protein Nhomocysteinylation. J Biol Chem. 2000;275:395762.
3. Jakubowski H. Pathophysiological consequences of homocysteine
excess. J Nutr. 2006;136:17419S.
4. Chwatko G, Jakubowski H. The determination of homocysteinethiolactone in human plasma. Anal Biochem. 2005;337:2717.
125
Poster Abstracts
P151
P152
Characterization of HIV-1 subtypes in a Portuguese cohort
Molecular epidemiology of HIV-1 strains in Antalya, Turkey
Nuno Rocha Pereira; Raquel Duro; Carmela Piñero; Luı́s Malheiro;
Jorge Soares; Rosário Serrão and António Sarmento
Infectious Diseases, Centro Hospitalar São João, Porto, Portugal.
Dilara Inan1 and Murat Sayan2
1
Infectious Diseases and Clinical Microbiology, Faculty of Medicine,
Akdeniz University Hospital, Akdeniz University, Antalya, Turkey.
2
Clinical Laboratory, PCR Unit, Kocaeli University Hospital, Kocaeli
University, Izmit-Kocaeli, Turkey.
Introduction: Distribution of HIV-1 subtypes is variable around the
world, with the most common subtype in western Europe being subtype B. The aim our study was to describe the prevalence of different
HIV-1 subtypes in newly diagnosed patients and identify demographic
and epidemiological characteristics related with different subtypes.
Materials and Methods: Retrospective single-centre study of patients
newly diagnosed with HIV-1 infection between 2006 and 2012.
Epidemiological data was gathered and genotyping was performed in
each patient identified. Demographic and epidemiological characteristics
were compared between patients with subtype B and other subtypes.
Continuous variables were summarized by mean and standard deviation
whereas categorical variables were presented as proportions. Comparison of groups was performed using the Chi square, Fisher exact test and
Student T test. Statistical significance was assumed when pB0.05.
Results: In the period of the study, 624 patients newly diagnosed
with HIV-1 infection were submitted to genotypic testing but information about subtype was available only for 592 patients. General
characteristics of the patients are summarized in Table 1. The distribution of the identified subtypes was the following: 286 (48.3%)
patients had subtype B, 157 (26.5%) had subtype G, 54 (9.1%) had
subtype C, 36 (6.1%) had subtype A, 32 (5.4%) had subtype F and 25
(4.2%) had CRF’s. Patients with subtype B were more commonly
male (p0.001) and younger (pB0.0001) than those with subtypes other than B. Subtype B was more common in MSM patients,
while non-B subtypes were more common in heterosexual patients
and in injecting drug users (p 0.001). CD4-cell count, viral load
and AIDS at presentation were not significantly different between
subtypes. Resistance associated mutations were significantly more common in patients with non-B subtypes (15.4% vs 9.8%; p0.048).
Conclusions: The most commonly identified subtype was B in
accordance with previous reports from other western European
countries. However, in our cohort the proportion of non-B subtypes
is higher than that reported for other European countries, probably
reflecting the influence of strong bonds with Portuguese speaking
African countries. Knowledge about HIV subtypes distribution may
help understanding transmission dynamics and can be an important
tool in the design of preventive measures.
Introduction: The aim of this study was to determine the subtype
distribution of HIV-1 strains isolated from antiretroviral therapy (ART)naive and on treatment patients in Antalya, the city of southern Turkey.
Materials and Methods: The study included 77 of 92 newly diagnosed HIV-1 positive patients of last two years (between February
2012 and June 2014). HIV-1 subtypes and circulating recombinant
forms (CRFs) were identified by phylogenetic analysis of reversetranscriptase (codon 41238) and protease (codon 199) domains
( 667 bp) of pol gene region in HIV-1 strains.
Results: Subtype B (48%, 37/77) was identified as the most common
HIV-1 subtype in Antalya that similar the other Turkish patients. NonB subtypes were followed as CRFs (39%, 30/77). Interestingly,
CRF14_BG (12.9%, 10/77) was found for the first time in Antalya in
contrast to previous observations in the other reports in Turkey. Also,
subtype G (6.5%, 5/77) was detected more often than HIV-1 subtypes
in circulation of Turkey.
Conclusions: These findings may be associated with specific geographic localization of Antalya that touristic movements of city.
Recognized HIV-1 subtype diversity is major challenges in the
development of a globally effective HIV vaccine.
References
1. Sayan M, Willke A, Ozgunes, Sargýn F. HIV-1 subtypes and primary
antiretroviral resistance mutations in antiretroviral therapy naive
HIV-1 infected individuals in Turkey. Jpn J Infect Dis. 2013;66:30611.
2. Yilmaz G, Midilli K, Turkoglu S, Bayraktaroǧlu Z, Kuşkucu AM,
Ozkan E, et al. Genetic subtypes of human immunodeficiency virus
type 1 (HIV-1) in Istanbul, Turkey. Int J Infect Dis. 2006;10:28690.
3. Alpsar D, Agacfidan A, Lubke N, et al. Molecular epidemiology of
HIV in a cohort of men having sex with men from Istanbul. Med
Microbiol Immunol. 2013;202:2515.
4. Hemelaar J. The origin and diversity of the HIV-1 pandemic. Trends
Mol Med. 2012;18:18292.
Abstract P151Table 1. General characteristics of the patients
Characteristics
Sex
Male
Female
Age (mean9SD)
n 592
P153
425 (71.8%)
167 (28.2%)
40.78913.45
Risk for HIV acquisition
Heterosexual
410 (69.5%)
MSM
132 (22.2%)
Injecting drug user
Others
CD4-cell count /mL (mean9SD)
HIV-1 Viral load copies/mL (mean9SD)
LABORATORY MONITORING OF DISEASE
AND THERAPY TROPISM ASSAYS
46 (7.8%)
2 (0.3%)
3209257
7,23,035919,70,266
MSM, Men that have sex with men; SD, Standard deviation; CD4,
CD4 T cell lymphocytes.
Plasma HIV-1 tropism and risk of short-term clinical
progression to AIDS or death
Maria Casadellà Fontdevila1; Alessandro Cozzi-Lepri2;
Andrew Phillips2; Marc Noguera Julian1; Marcus Bickel3;
Dalibor Sedlacek4; Gitte Kronborg5; Adriano Lazzarin6; Kai Zilmer7;
Bonaventura Clotet1; Jens D Lundgren8 and Roger Paredes1
1
IrsiCaixa AIDS Research Institute, Barcelona, Spain. 2Royal Free
Hospital, London, UK. 3Goethe University, Frankfurt, Germany.
4
Charles University Hospital, Plzen, Czech Republic. 5Hvidovre,
Copenhagen, Denmark. 6Ospedale San Raffaele, Milano,
Italy. 7West-Tallinn Central Hospital, Tallinn, Estonia. 8Panum
Institute, Copenhagen HIV Programme, Copenhagen, Denmark.
Introduction: It is uncertain if plasma HIV-1 tropism is an independent predictor of short-term risk of clinical progression / death, in
126
addition to the CD4 count and HIV RNA level. We conducted a nested
case-control study within EuroSIDA to assess this question amongst
people with current HIV RNA level 1000 copies/mL, including both
people on ART and those ART naı̈ve.
Methods: People with an AIDS diagnosis or who died from any
causes for whom there was a stored plasma sample with HIV-1 RNA
(VL) ]1,000 copies/mL available in the time window of 312 months
prior to the event were identified. At least one control was selected
for each case matched for age, VL and HCV status at the time of
sampling. Controls were event-free after a matched duration of time
from the date of sampling. Plasma HIV tropism was estimated using
454 and population sequencing (PS). Non-R5 HIV was defined as: (a)
]2% of sequences with a Geno2Pheno (G2P) FPR 53.75% by 454,
and (b) a G2P FPR510% by PS. We also compared CD4 slopes over
the 12 months following the date of sampling using a linear mixed
model with random intercept according to HIV tropism and ART
status.
Results: The study included 266 subjects, 100 cases and 166 controls,
with sample taken on average in 2006; 23% and 24% had non-R5
HIV by 454 and PS respectively. There were 19% women, 25%
MSM, 92% Caucasians, 22% HCV. At the time of sampling, 26% were
ART-naı̈ve, 25% had started but were off ARTand 49% were receiving ART.
The median age, CD4 and viral load was 41 years, 350 cells/mm3 and
4.81 log c/mL, respectively. Baseline characteristics were well balanced by
tropism. Factors independently associated with clinical progression or
death were female gender (OR2.12; 95% CI1.04, 4.36; p0.038),
CD4 count (OR0.90 per 100 cells/mm3 higher; 95% CI 0.80, 1.00;
p0.058), being on ART (OR2.72; 95% CI 1.15, 6.41; p0.022) and
calendar year of sample (OR0.84 per more recent year; 95% CI0.77,
0.91; pB0.001). Baseline plasma tropism was not an independent risk
factor for clinical progression or death by either 454 or PS. No significant
interaction was observed between tropism and ARTstatus.There were no
significant differences in the CD4 slope within or between tropism
groups.
Conclusions: Plasma HIV-1 tropism does not appear to add to the
ability of CD4 count and viral load to predict the short term risk of
AIDS and death outcomes, even with 454 sequencing.
P154
Using dried blood spots collected under field condition to
determine HIV-1 diversity and drug resistance mutations in
resource limited Tanzania
James Kimaro1; Elichilia Shao1; Balthazar Nyombi1; Emanuel Kifaro1;
Dorcas Maruapula2; Simani Gaseitsiwe2 and Rosemary Musonda2
1
Clinical Laboratory, Kilimanjaro Christian Medical Centre, Moshi,
Tanzania. 2HIV Research Lab, Botswana Harvard HIV Research Lab,
Gaborone, Botswana.
Introduction: A dried blood spot (DBS) on filter paper has been used
for different tests globally and has gained popularities in resource
limited settings especially during HIV/AIDS epidemic. We assessed
the efficiency of molecular characterization of HIV-1 subtypes using
DBS collected under field conditions in northern Tanzania.
Material and Methods: In 2011 and 2012, 60 DBS samples were
collected under field conditions from exposed and newly diagnosed
HIV-1 infected children from Kilimanjaro (n 20), Arusha (n 20),
Tanga (n 10) and Manyara (n10).
Results and discussion: Of 60 DBS analyzed at both Protease (PR)
and Reverse Transcriptase (RT) regions, 45 (75%) were analyzed,
including 17 (85%) from Kilimanjaro, 15 (75%) from Arusha, 8
(80%) from Tanga, and 5 (50%) from Manyara region. All 45 DBS
characterized had viral load above 1000 copies/mL with mean log10
viral loads of 3.87 copies/mL (SD 0.995). The phylogenetic results
Poster Abstracts
indicated presence of subtype and circulating recombinant form
(CRF). In which, 24 were subtype A1 (53.33%), 16 were subtype C
(35.55%), 3 were subtype D (6.67%) and 2 were CRF10_CD (4.35%).
All major mutations were detected in the RT region, none from
protease (PR) region. The mutations detected were Y181C (n 8),
K103 (n4) and G190A (n1), conferring resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs), and M184V
(n 1), conferring resistance to lamivudine and emtricitabine.
Conclusions: Our results indicate that DBS collected from field
conditions in resource scarcity areas can be used to determine the
phylogeny of the virus and drug resistance mutations in areas with
diverse HIV-1 group M subtypes.
P155
Temporal increase in HIV-1 non-R5 tropism frequency
among antiretroviral-naive patients from northern
Poland
Milosz Parczewski; Magdalena Leszczyszyn-Pynka;
Magdalena Witak-Jêdra; Katarzyna Maciejewska and Anna Urbañska
Department of Infectious, Tropical Diseases, Pomeranian Medical
University in Szczecin, Szczecin, Poland.
Introduction: Sequencing of the third hypervariable loop allows to
identify genotype-based HIV tropism. R5-tropic viruses associated
with early stages of infection are preferentially transmitted, while
non-R5 HIV-1 tropism has been associated with severe immunodeficiency and lower lymphocyte CD4 nadir and may reflect delayed
HIV diagnosis. In this study, we investigate the changes in tropism
frequency from 2007 to 2013.
Material and Methods: Study included 194 patients with confirmed
HIV infection linked to care in 20072013. Baseline plasma samples from treatment naive patients were used for HIV-1 genotypic
tropism assessment based on triplicate V3 loop sequencing. Non-R5
tropism prediction thresholds were assigned using a false positive
rate (FPR) of 10% and 5.75% FPR and associated with clinical
and laboratory data (age, gender, date of HIV diagnosis, route of
transmission, CDC clinical category at diagnosis, pretreatment
HIV viral load, baseline and nadir lymphocyte CD4 counts). For
statistics, chi-square and MannWhitney U tests were used, time
trends were examined using logistic regression (R statistical platform, v. 3.1.0) for binary variables and linear regression for
continuous ones.
Results: Overall non-R5 tropism frequency for the 5.75% FPR was
15.5% and 27.8% for 10% FPR. Frequency of the non-R5 tropism
predicted using 5.75% FPR increased significantly from 2007 (0%) to
2013 (25%) [OR: 1.44 (95% CI 1.141.86), p0.003, rough slope
3.89%/year] (Figure 1a). With 10% FPR, the frequency changed
from 7% (2007) to 33% (2013) [OR: 1.17 (95% CI 0.991.39),
p0.054, rough slope 3.0%/year] (Figure 1b). Baseline lymphocyte CD4 count and nadir, as well as pretreatment HIV-1 viral loads
were stable over time of observation (r 0.014, p0.84; r 0.13,
p0.085; r0.016, p0.83 for CD4 baseline, nadir and HIV load,
respectively). Frequency of AIDS at HIV diagnosis increased from
21.4% in 2007 to 38.0% in 2013, however trend over time was
insignificant [OR: 1.1 (95% CI 0.951.31), p0.19]. Temporal trends
for HIV transmission route, gender, non-B variant frequencies also
were not significant.
Conclusions: R5 tropism predominates among the treatment naive
individuals but increase in the frequency of non-R5 tropic variants
may limit clinical efficacy of the coreceptor inhibitors. Increased
prevalence of non-R5 HIV-1 may be related to late care entry and
higher number of AIDS diagnoses in the recent years.
127
Poster Abstracts
Abstract P155Figure 1. Logistic regression analysis of the V3 loop genotype-based HIV-1 tropism frequency: (a) tropism frequencies with
PFR 5.75%; (b) tropism frequencies with 10% PFR. Observed tropism frequencies are shown as bars with superimposed logistic regression
curve.
LATE PRESENTERS
P156
Evolution trends over three decades of HIV infection late
diagnosis: the experience of a Portuguese cohort of
705 HIV-infected patients
Ana Claudia Miranda; Virginia Moneti; Pedro Brogueira;
Susana Peres; Teresa Baptista; Isabel Aldir; Fernando Ventura;
Fernando Borges and Kamal Mansinho
Serviço de Infecciologia e Medicina Tropical, Hospital Egas
Moniz Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal.
Introduction: Late HIV diagnosis is common and associated with an
increased risk of clinical progression, blunted immune response on
antiretroviral (ARV) therapy and higher risk of drug toxicity. Across
Europe, more than a third of patients are diagnosed late and consequently delay medical care. European Consensus definition group
identify as late presentation (LP) persons, presenting for care, with
a CD4 count below 350 cell/mm3 or presenting with AIDS-defining
event, regardless of CD4 cell count. Additionally, advanced HIV disease (AD) is defined by a CD4 count below 200 cell/mm3 or an AIDS
defining condition in persons presenting to care.
Material and Methods: Retrospective observational study of a
cohort of 705 HIV-infected patients diagnosed between 1986 and
2014 and medically followed at an Infectious Diseases Service in
Lisbon.
Objectives: Evaluate LP rate evolution in the last three decades
(10-year time intervals considered: 19861995; 19962005; 2006
2014); compare clinic, immunologic, virologic and therapeutic
response over time. Identify main reasons responsible for late HIV
diagnosis in order to promote optimized intervention strategies. SPSS
version 20.0 was used for statistical analysis.
Results: Study included 705 patients HIV diagnosed during 3 time
intervals: group A n82 [19861995]; group B n332 [1996
2005]; group C n291 [20062014]. Demographic and epidemiological characterization revealed (A vs B vs C): male predominance of
79% vs 66% vs 66%; mean age at diagnosis 30 vs 36 vs 42 years;
Portugal (82% vs 70% vs 58%) and Africa (13% vs 23% vs 29%) as the
main places of birth; transmission by heterosexual contact in 21% vs
47% vs 62%, MSM in 21% vs 15% vs 23% and IVDU in 57% vs 35% vs
13%. Mean CD4 at diagnosis was 362 vs 344 vs 377 cell/mm3.
Considering the time intervals, LP was found in 52% vs 56% vs 52% of
patients and AD in 31% vs 38% vs 35%, respectively. At first health
care encounter, 46% vs 43% vs 39% of individuals presented with
AIDS. Over follow up, the vast majority initiated ARV (95% vs 98% vs
84%) and mean CD4 at that time was 254 vs 282 vs 250 cell/mm3.
The last immunologic and virologic determination available registered mean CD4 of 657 vs 644 vs 584 cell/mm3 and undetectable HIV
plasma RNA in 92% vs 84% vs 82% of treated patients.
Conclusions: This study evidenced a maintained LP rate, slightly
above 50% in each of the three analyzed last decades, and one-third
of patients presented AD at HIV diagnosis. At initial health care
contact, nearly 40% of individuals met AIDS clinical or immunological
criteria.
P157
Intermittent viraemia and immune reconstitution in
patients with more than 1015 years of antiretroviral
therapy: baseline values still matter
Gesa Erdbeer1; Michael Sabranski2; Ina Sonntag1; Albrecht Stoehr3;
Heinz-A Horst1; Andreas Plettenberg3; Knud Schewe2; Stefan Unger3;
Hans-J Stellbrink2; Stefan Fenske2 and Christian Hoffmann2
1
University of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
2
Infektionsmedizinisches Centrum Hamburg, Study Center, Hamburg,
Germany. 3IFI, Institute for Interdisciplinary Medicine, Hamburg,
Germany.
Introduction: Data on patients with long-term exposure to ART is
scarce because controlled studies usually do not follow up patients for
more than five to seven years. We were interested whether baseline
parameters such as CD4 T-cell nadir or pre-treatment viraemia do have
an impact on ART success after more than a decade of treatment.
Methods: ELBE is a cross-sectional study on adult HIV patients
presenting consecutively with viral suppression (B50 HIV RNA
copies/mL) and with ART exposure of at least five years. In this
sub-analysis, all patients with more than 10 years of ART exposure
were evaluated for immune reconstitution and for intermittent
128
transient viraemia (501000 copies/mL, defined as ‘‘blips’’) during
the last five years.
Results: From a total of 894 patients included in the three participating ELBE centres, 524 patients had an ART exposure of at least
10 years and had been treated continuously during the last 5 years.
Of these, 33.4% had at least one ‘‘blip’’ while 63.5% did not show
any transient viraemia of more than 50 copies/mL. Patients with at
least one blip had a higher pre-treatment viraemia compared to
patients without blips (5.30 versus 5.06 log copies/mL, p0.0003).
In patients with a pre-treatment viraemia of more than 100,000,
50,000100,000 and less than 50,000 copies/mL, the proportions of
patients with blips during the last five years were 39.5%, 30.5%
and 21.8% (p0.007), respectively. The history of an AIDS-defining
illness or the CD4 T-cell nadir was not associated with a higher
frequency of blips. However, CD4 T-cell nadir was a strong predictor
for current CD4 T-cell counts. In patient groups with a CD4 T-cell
nadir of 099, 100199, 200349, 350 cells/mL, the median
current CD4 T cells were 571, 667, 710 and 890 cells/mL, respectively. These differences remained significant when the analysis
was restricted to patients with more than 15 years of ART exposure
(n 268).
Conclusions: In this large group of positively selected HIV patients
with long-term exposure to ART of at least 1015 years, high pretreatment viraemia was still associated with a higher frequency of
intermittent transient viraemia (‘‘blip’’). A low CD4 T-cell nadir
remained associated with a lower CD4 cell recovery. The clinical
implications of these findings remain to be evaluated.
P158
Characteristics of late presentation of HIV infection
in MSM and heterosexual adults in Portugal
20112013
Tara Shivaji1; Antonio Diniz2 and Helena Cortes-Martins3
1
European Programme for Interventional Epidemiology Training
(EPIET), Directorate General of Health, Lisbon, Portugal. 2HIV/AIDS
Programme, Directorate General of Health, Lisbon, Portugal. 3HIV/
AIDS Surveillance, Instituto Nacional de Saúde, Doutor Ricardo Jorge,
Lisbon, Portugal.
Introduction: It is estimated that over half of newly diagnosed HIV
infections in Europe present late. An HIV positive individual presenting late to care represents a missed opportunity to benefit from
treatment, increasing the risk of morbidity and mortality at an
individual level, and onward disease transmission at population level.
Reducing late presentation is a strategic priority of the Portuguese
HIV/AIDS program. We set out to describe the characteristics of late
presentation in the two largest transmission risk groups currently in
Portugal to inform HIV prevention and treatment.
Methods: We extracted details of all notified cases from individuals
over 15 years with a laboratory confirmed HIV diagnosis made
between January 2011 and December 2013 from the Portuguese HIV
surveillance database and selected cases from heterosexuals and
men who have sex with men (MSM). We defined late presentation as
an initial CD4 count B350 cells/mm3 or presence of AIDS-defining
disease at time of HIV diagnosis. We calculated adjusted odds ratios
(aOR) with 95% confidence intervals (CI) for characteristics associated with late presentation in separate logistic regression for
heterosexuals and MSM.
Results: Of 4219 HIV positive cases notified, 2589 (61%) were
heterosexuals and 1220 (29%) were MSM. A total of 1586 (38%)
cases presented late of which 1037 (40%) were heterosexual and 328
(27%) were MSM. The median age at late presentation was 40 in
heterosexual women, 46 in heterosexual men and 35 in MSM. A total
Poster Abstracts
of 1446 (55%) of heterosexual HIV positive adults were unaware of
having had a high risk sexual contact. Late presentation among
heterosexuals was associated with being male (aOR 1.58 95% CI
1.291.93), not knowing a partners’ HIV status (OR 1.59 95% CI
1.351.87) and age, increasing the odds of late presentation by a
factor of 1.02 per year (95% CI 1.011.03). Among MSM, only age
was associated with late presentation, increasing by 1.04 (95% CI
1.031.05) per year.
Conclusions: Portuguese HIV prevention programs need to increase
the risk awareness of heterosexuals, particularly men, to reduce
missed opportunities for early diagnosis. As half of all cases presenting late are aged 40 and over, we recommend that general
HIV outreach services and specialist services for MSM review
their accessibility and acceptability to both middle and older-aged
clients.
P159
Characteristics of late presenters in Bucharest
Raluca Elena Jipa1; Eliza Manea1; Serban Benea2; Iulia Niculescu1;
Otilia Benea2; Mariana Mardarescu3; Cosmina Andrei2;
Ruxandra Moroti1 and Adriana Hristea1
1
Clinical Department III, National Institute of Infectious Diseases
‘‘Prof. Dr. Matei Bals’’, Bucharest, Romania. 2Clinical Department V,
National Institute of Infectious Diseases ‘‘Prof. Dr. Matei Bals’’,
Bucharest, Romania. 3Clinical Department VIII, National
Institute of Infectious Diseases ‘‘Prof. Dr. Matei Bals’’,
Bucharest, Romania.
Introduction: Late presentation is associated with increased healthcare costs, rates of HIV transmission and poor outcome. In Romania,
in 2012, one third of individuals with new HIV diagnosis were late
presenters (LP).
Objective: The aim of the study was to evaluate the epidemiological
and clinical characteristics associated with late presentation.
Methods: We retrospectively studied patients over 18 years old, notified in our institution between January 2012 and December 2013,
including 499 out of 727 newly diagnosed patients in Bucharest. LP
were defined as patients presenting with CD4 T-cell count below 350
cells/mm3 or with an AIDS defining event. Patients with advanced
HIV disease (AHD) were defined as persons with a CD4 T-cell count
below 200 cells/mm3. Differences between groups were analyzed
using the Mann-Whitney U test for continuous variables and the chisquare test for dichotomous variables. Multivariable analysis was
performed using binary logistic regression.
Results: Out of 499 patients included, 362 (72%) were male. The
median age was 30 (IQR 2636). A total of 302 (61%) were LP and
184 (37%) were patients with AHD. A total of 170 (34%) were
asymptomatic and 114 (23%) presented with an AIDS-defining
event. The median CD4 count was 293 cells/mm3 (IQR 125471)
and the median HIV viral load was 100,191 copies/mL (IQR 34,560
272,936). Characteristics of LP compared with non-LP are shown
in Table 1. Stage C disease has been shown by multivariable
analysis to be associated with LP (p B0.001, OR 11.56, 95% CI
4.9427.03).
Conclusions: More than half of newly HIV diagnosed patients in
Bucharest were LP. The proportion of LP was highest among heterosexually acquired cases. Although most our patients were young,
late presentation was associated with age over 35 years. The lower
proportion of LP among IVDU compared with those heterosexually
infected could be explained by a higher proportion of HIV screening
tests among IVDU.
129
Poster Abstracts
Epidemiological, clinical and laboratory characteristics in late presenters versus non-late presenters
Late presenters, N302
Male, N (%)
Non-late presenters, N197
p value; OR [95% CI]
214 (71)
148 (75)
32 (2738)
29 (2534)
B0.001
Age]35 years, N (%)
105 (35)
38 (19)
B0.001; 2.2 [1.43.4]
Level of education-under 8th grade, N (%)
146 (48)
122 (62)
0.003; 0.5 [0.30.8]
Transmission mode: IVDU, N (%)
124 (41)
111 (56)
0.001; 0.5 [0.30.7]
Transmission mode: Heterosexual, N (%)
149 (49)
68 (35)
0.001; 1.8 [1.22.6]
Transmission mode: MSM, N (%)
Stage A, N (%)
28 (9)
107 (35)
20 (10)
141 (72)
0.174; 1.6 [0.83]
B0.001; 0.2 [0.10.3]
Stage B, N (%)
88 (29)
49 (25)
0.307; 0.8 [0.51.2]
Stage C, N (%)
107 (35)
7 (4)
B0.001; 14.8 [6.732.8]
Age (years) (median, IQR)
0.307; 1.2 [0.81.8]
HIV-RNA]100,000 copies/mL, N (%)
199 (66)
103 (52)
0.003; 1.7 [1.22.5]
Chronic hepatitis C, N (%)
129 (43)
118 (60)
B0.001; 0.5 [0.30.7]
Chronic hepatitis B, N (%)
38 (13)
22 (11)
0.67; 1.1 [0.62]
Mortality, N (%)
40 (13)
6 (3)
B0.001; 4.8 [2.112.8]
IQR Interquartile range; IVDU Intravenous drug users; MSMmen having sex with men.
P160
Late diagnosis among our ageing HIV population: a cohort
study
Sarah Mensforth1; Lisa Goodall1; Neena Bodasing2 and
James Coultas3
1
Stoke and Staffordshire Partnership Trust, Cobridge Sexual Health,
Stoke-on-Trent, UK. 2Infectious Diseases, University Hospital of
North Staffordshire, Stoke-on-Trent, UK. 3University Hospital of
North Staffordshire, Keele University School of Medicine,
Stoke-on-Trent, UK.
Introduction: With the advent of combined antiretroviral therapy
(cART), more people infected with HIV are living into older age;
22% of adults receiving care in the UK are aged over 50 years [1].
Age influences HIV infection; the likelihood of seroconversion illness, mean CD4 count and time from infection to development of AIDs
defining illnesses decreases with increasing age. A UK study estimates
that half of HIV infections in persons over 50 years are acquired at an
age over 50 [2]. Studies exploring sexual practices in older persons have
repeatedly shown that we cannot assume there is no risk of STI and HIV
infection [3,4]. Physicians should be alert to risk of HIV even in the older
cohort, where nearly half diagnoses are made late [2]. Local audit has
demonstrated poor testing rates in the over 50’s on the Acute Medical
Unit. Late diagnosis (CD4B350) results in poorer outcomes and age
confounds further; older late presenters are 2.4 times more likely to die
within the first year of diagnosis than younger counterparts [2].
Materials and Methods: A retrospective case notes review was
conducted of all patients aged 60 years and over attending HIV clinic
in the last 2 years. Outcomes audited included features around
diagnosis; age, presentation, missed testing opportunities and CD4
count at diagnosis.
Results: Of the current cohort of 442 patients, 34 were over 60 years
old (8%). Age at diagnosis in this group ranged from 36 to 80 years,
mean 56.6 years. Presentation triggers included opportunistic infections or malignancies (n 10), constitutional symptoms (n 6),
diagnosis of another STI (n 4), seroconversion illness (n2), partner
status (n3). Eight patients were diagnosed through asymptomatic
screening at Sexual Health. We identified missed opportunities in five
patients who were not tested despite diagnoses or symptoms defined
as clinical indicators for HIV. Half of older patients had a CD4 count of
B200 at diagnosis.
Conclusions: It is imperative that general medical physicians and
geriatricians are alert to enquiring about risk and testing for HIV
where clinical indicators are present, irrespective of age. The oldest
patient in the cohort was diagnosed with HIV aged 80 years. All
patients with missed opportunities for testing were over 47 years old.
References
1. Health Protection Agency. HIV in the United Kingdom: 2012 report
[cited July 2014]. Available from: http://www.hpa.org.uk/Publications/
InfectiousDiseases/HIVAndSTIs/1211HIVintheUK2012/
2. Delpech VC, Brown AE, Rice BD, Smith RD. HIV transmission and
high rates of late diagnoses among adults aged 50 years and over.
AIDS. 2010;24(13):210915.
3. The National Survey of Sexual Attitudes and Lifestyles. 2012 [cited
July 2014]. Available from: http://www.natsal.ac.uk/natsal-3.
4. Bodley-Tickell AT, Olowokure B, Bhaduri S, White DJ, Ward D, Ross
JD, et al. Trends in sexually transmitted infections (other than HIV) in
older people: analysis of data from an enhanced surveillance system.
Sex Transm Infect. 2008;84:3127.
MOTHER-TO-CHILD TRANSMISSION
P161
Pregnancy outcomes in women growing up with perinatally
acquired HIV in the United Kingdom and Ireland
Laura Byrne1; Claire Thorne1; Caroline Foster2 and Pat Tookey1
1
Policy and Practice Programme, UCL Institute of Child Health,
Population, London, UK. 2Paediatric Infectious Diseases, Imperial
College Healthcare NHS Trust, London, UK.
Introduction: In the United Kingdom and Ireland more than 40% of
individuals living with perinatally acquired HIV are now aged 16.
Globally, increasing numbers of women with perinatally acquired
HIV are becoming pregnant, but data on fertility and pregnancy
outcomes is scarce. We present pregnancy outcome data for this
emerging cohort.
Methods: Pregnancies in diagnosed HIV-infected women in the
United Kingdom and Ireland, and children diagnosed with HIV, are
130
reported to the National Study of HIV in Pregnancy and Childhood.
We analyzed data on pregnancies in women diagnosed aged 513
with perinatally acquired HIV, reported by June 2014.
Results: A total of 759 females born before 2001, diagnosed with
perinatally acquired HIV aged 513 years, and in care in the UK and
Ireland have been reported. Forty-four of these (6%) have had at
least one pregnancy reported, with nineteen 2nd and four 3rd/4th
pregnancies. Women’s year of birth ranged from 1985 to 1996; 60%
of women were UK/Irish-born and 39% African-born. Twenty one
percent were diagnosed at B2 years, 39% at 27 and 41% at 813
years. Nine pregnancies were conceived in 200507, 22 in 200810
and 36 in 201113. Median age at conception of first pregnancy was
19 years. CD4 count was 500 cells/mL in 36% of first pregnancies,
350499 in 15% and B350 in 49%. Women were on antiretroviral
therapy (ART) at conception in 71% of pregnancies. There were 51
singleton live births, 2 miscarriages, 9 terminations and 5 continuing
to term. In 17 live births to women not on ART at conception,
median gestational age at start of ART was 17 weeks (range 329).
HIV viral load was B50 copies/mL near delivery in 64% of live births,
511000 in 31% and 1000 in 5%. Forty four percent of live births
were delivered by elective caesarean section (CS), 27% by emergency
CS, 27% by planned vaginal delivery and with one unplanned vaginal
delivery. Of 29 live births with viral load B50, 31% were delivered by
elective CS, 17% by emergency CS and 52% by vaginal delivery.
Fifteen percent of infants were delivered at 3236 weeks gestation,
and 2% at 30 weeks; 16% weighed 1.52.5 kg and 16% weighed
B1.5 kg. Among 38 of the 51 infants where infection status is
already reported, one is perinatally infected.
Conclusions: Currently at least 6% of perinatally infected women
in care in the UK and Ireland have experienced one or more
pregnancies. Linking paediatric, pregnancy and second generation
data will enable further monitoring of pregnancy outcomes in this
newly emerging population.
P162
The effect of tenofovir on renal function in HIV-positive
pregnant women
Stuart Flanagan1; Lynne Barnes2; Jane Anderson1 and Tristan Barber1
1
Department of Sexual Health and HIV medicine, Homerton
University Hospital, London, UK. 2Department of Obstetrics and
Gynaecology, Homerton University Hospital, London, UK.
Introduction: Tenofovir is a commonly used component of antiretroviral therapy (ART) to reduce vertical transmission of HIV.
Although systematic review of tenofovir use in pregnancy concluded
it to be low risk for foetal abnormalities [1], data is limited on its
impact on renal function in pregnant women. A recent South African
study [2] concluded that renal dysfunction in HIV-infected pregnant
Poster Abstracts
women is significantly less common than in other HIV-infected
adults, however there is currently no UK data. We aimed to
investigate the effect of tenofovir on renal function in HIV-1 positive
pregnant women in a UK clinic.
Methods: We retrospectively analyzed data on renal function in
pregnancy from a cohort of women attending a busy inner city
London antenatal clinic. All women were screened for renal function
throughout pregnancy via serum creatinine and estimated glomerular filtration rate (eGFR) calculated using modification of diet in
renal disease (MDRD) and corrected for ethnicity.
Results: Ninety-seven HIV-1 positive women were registered at
Homerton Hospital antenatal service of a total of 105 pregnancies
between January 2010 and September 2013. Tenofovir was prescribed in 71/105 pregnancies (67.6%). Of the 71 pregnancies, 41
were prescribed tenofovir pre-conception (57.7%). Of the pregnant
women who started tenofovir in pregnancy, 21/31 (67.7%) were
initiated before week 24 of pregnancy, in line with British HIV association (BHIVA) guidelines [3]. There was no deterioration in median
serum creatinine or decline in eGFR in women prescribed tenofovir
during pregnancy. At six weeks after delivery, in the 42 women who
continued tenofovir therapy and had eGFR measured, one woman
had eGFR 60, all others eGFR 90 (Table 1).
Conclusions: Consistent with current guidelines and experience, this
study shows tenofovir did not cause decline in renal function in
pregnancy in our cohort of HIV-1 positive women, whether started
during pre-conception or during pregnancy. More evidence should
be prospectively collected looking at effects of tenofovir on other
measures of tubular renal function in pregnancy such as proteinuria
and protein-creatinine ratio.
References
1. Wang L, Kourtis AP, Ellington S, Legardy-Williams J, Bulterys M.
Safety of tenofovir during pregnancy for the mother and fetus:
a systematic review. Clinical Infectious Diseases Dec. 2013;57(12):
177381.
2. Myer L, Kamkuemah M, Kaplan R, Bekker LG. Low prevalence of
renal dysfunction in HIV-infected pregnant women: implications for
guidelines for the prevention of mother-to-child transmission of HIV.
Tropical Medicine & International Health Nov. 2013;18(11):14005.
3. Management of HIV infection in pregnancy women BHIVA
Guidelines 2012.
P163
The use of TDM in pregnant HIV-positive women: a
retrospective cross-sectional review of five years
practice in two large hospitals in Manchester
Thomas Whitfeld1; Amabel Dessain2; Kelly Taylor3; Orla McQuillan2;
Evelyn Looi4; Margaret Kingston2 and Katherine Ajdukiewicz4
Abstract P162Table 1. Renal function during pregnancy
Gestation (weeks)
No. (% of those prescribed tenofovir)
Median serum creatinine (Range)
eGFR90 (%)
eGFRB90
12
45 (100%)
55 (4664)
100
0
20
44 (73.3%)
53 (4462)
100
0
24
47 (75.8%)
53 (4465)
100
0
28
32
54 (79.4%)
54 (76.0%)
54 (4370)
55 (4169)
100
100
0
0
36
58 (81.6%)
56 (4682)
99.98%
0.017%
6 weeks Postnatal
42 (63.6%)
60.5 (4581)
99.97%
0.024%
131
1
Infectious Diseases, North Manchester General Hospital,
University of London, Manchester, UK. 2Manchester Centre
for Sexual Health, Genitourinary Medicine, Manchester, UK.
3
Paediatrics, North Manchester General Hospital, Manchester,
UK. 4Infectious Diseases, North Manchester General Hospital,
Manchester, UK.
Introduction: Despite plasma levels of certain HIV drugs decreasing
in the third trimester of pregnancy there is no definitive evidence
that therapeutic drug monitoring (TDM) improves HIV control and
prevents mother-to-child transmission (MTCT). Indeed ‘‘one-off’’
TDM measurements are thought to poorly correlate with overall
drug exposure [1]. We aim to describe baseline demographic and
clinical characteristics of pregnant women with HIV, and to compare
their HIV control, management during pregnancy and neonatal outcomes with respect to whether TDM was performed.
Materials and Methods: Retrospective cross-sectional case note
analysis was performed on pregnant women with HIV who attended
North Manchester General Hospital and Manchester Royal Infirmary
from 1st January 2008 to 28th May 2013.
Results: A total of 171 pregnancies were included; 39% (n 66) had
TDM. The majority of patients were of African origin (85%) and age
range was 1642 years (median 32 years). TDM was found to be
associated with a history of poor adherence to therapy (TDM 23%, vs
no TDM 10%, p 0.017), although baseline viral load (VL) and CD4
counts were comparable between TDM and non-TDM groups
(p 0.4756 and 0.9492, respectively). TDM was also associated with
protease inhibitors (PI) (TDM 94% vs no TDM 77%, p 0.004). Within
the PI group, TDM was more strongly associated with atazanavir use
than other PI’s (55%, p 0.023). TDM was not associated with any
other demographic variable or with either of the two hospital sites
(p 0.427). TDM was associated with medication alterations during
pregnancy (TDM 67% vs no TDM 13%, p0.052), but was not
associated with any difference in outcomes with similar proportions of
newly detectable VL during pregnancy (TDM 12% vs no TDM 7%,
p0.220) and VL detectable at birth (TDM 14% vs no TDM 9%, p
0.293). There were no instances of MTCT.
Conclusions: TDM was associated with PI use and a history of
poor adherence at baseline. TDM was not associated with improved HIV control during pregnancy and there was no MTCT. TDM was
not shown to have any additional benefit in pregnancy and its
routine use is not recommended to improve HIV control or reduce
MTCT.
Reference
1. Cattaneo D, Ripamonti D, Baldelli S, Cozzi V, Fucile S, Clementi E.
Limited sampling strategies for the estimation of atazanavir daily
exposure in HIV-infected patients. Fundam Clin Pharmacol. 2013;
27(2):21622.
P164
Morbidity and mortality in HIV-exposed under-five children
in a rural Malawi setting: a cohort study
Oscar Divala1; Charles Michelo1 and Bagrey Ngwira2
1
Department of Public Health, School of Medicine, University of
Zambia, Lusaka, Zambia. 2Department of Community Health, College
of Medicine, University of Malawi, Blantyre, Malawi.
Introduction: Paediatric HIV infection significantly contributes to
child morbidity and mortality in southern Africa. In Malawi as in
most countries in the region, care of HIV-exposed children is constrained by the lack of area-specific information on their risk to dying
and morbidity. This research estimates and compares morbidity and
Poster Abstracts
mortality events between HIV-exposed and -unexposed under-five
children in a rural Malawian setting.
Methods: Data for children under the age of five collected from
January 2009 to June 2011 at a demographic and health site in
Karonga district of northern Malawi were analyzed. Morbidity and
mortality rates among HIV-exposed and -unexposed children were
calculated and compared using Kaplan-Meier survival analysis and
Cox proportional hazard regression.
Results: Overall (n 7,929) cohort data of under-five children born
in a demographic and health site represented 12380.8 person years
of observation (PYO) of which 3.1% were contributed by HIV-exposed
infants. Females accounted for half of the sample, and the overall
mean age was 18.4 months (SD 13.4) with older children in the HIV
unexposed group. All-cause morbidity rate was 337.6/1000 PYO (95%
CI 327.5/1000348.0/1000) and HIV-exposed children morbidity rate
was 1.34 times higher (pB0.001) compared to HIV-unexposed
children. integrated management of childhood illness (IMCI) pneumonia was the most common diagnosis (39.3%) in this cohort. Child
mortality rate was 16.6/1000 PYO (95% CI 14.519.1) from 206
deaths. HIV-exposed children had 4.5 times higher (pB0.001)
mortality rate compared to the HIV-unexposed children. Higher
mortality rates were observed in children under one year (129.2/
1000 PYO) compared to older age groups.
Conclusion: HIV exposure at birth has a greater impact on child morbidity and mortality especially in the first year of life. This underscores the need for targeted and synergetic interventions that
included focused prevention of mother-to-child transmission
(PMTCT) which could reduce HIV transmission to children in their
infancy in this setting.
P167
Severe birth defects in children perinatal exposed to HIV
from a ‘‘real-world’’ setting: Infectious Diseases National
Institute, Bucharest, Romania
Ana Maria Tudor
Paediatric Department, Matei Bals Inf Dis Nat Inst, Carol Davila
University for Medicine and Pharmacy, Bucharest, Romania.
Introduction: The shift in epidemic trends in recent years in Romania
shows new problems in regard of HIV vertical transmission, firstly in
intravenous drug user’s mothers co-infected with hepatitis viruses
and with social problems, and secondly the children of young mothers
with an old HIV infection and long antiretroviral therapy history.
Materials and Methods: We studied all HIV perinatal exposed
children routinely followed up in the Paediatric Department of the
National Institute of Infectious Diseases, since January 1st 2006 till
December 31st 2012. The analyses consisted of describing the birth
defects and association with certain risk factors: gender, mother’s
age at birth and exposure to antiretrovirals in the first trimester of
pregnancy.
Results: We analyzed 244 children born to HIV-infected mothers. The
incidence of HIV infection was 16.39%. The rate of birth defects was
39.34% (96/244 cases). The most frequent findings were cardiac
malformations (47/96), followed by musculoskeletal defects (24/96),
neurologic defects (20/96), urogenital malformations (13/96), digestive tract defects (3/93), metabolic disorders (2/96) and genetic
disorders (2/96). We found nine cases of severe congenital anomalies: complex heart defect, total congenital aganglionic megacolon, anal imperforation, Dandy-Walker syndrome, gangliosidosis,
Niemann-Pick syndrome, Down syndrome, true hermaphroditism
and cleft palate. Two children died during first year of life due to
severe malformations. 9% of cases had associated malformations.
The gender rate was in favour of males in group with birth defects
132
(58/38) and with no birth defects (82/66). The median age at birth in
mothers was 22 years, similar in both groups. The highest mean age
at birth was in offspring’s mothers with neurologic congenital defects
25, 15 years old, but is not statistically significant (p 0.1). In the
studied period the highest number of birth defects were found in
2012, 37 children, compared with less than 15 in previous years (not
statistically significant, p0.07). In our studied patients the risk of
birth defects was not statistically associated with HIV transmission or
with exposure to antiretrovirals before and in first trimester of
pregnancy (p0.88).
Conclusion: The rate of birth defects among HIV-exposed children
was not significantly associated with antiretroviral exposure, but we
identify very rare and severe congenital conditions. We have noticed
also a trend to increasing number of birth defects in 2012 among
studied patients compared to previous years.
P168
Poster Abstracts
treatment, due to mothers’ poor adherence to a basic set of cares
destined for their children.
Conclusions: Prevention programmes in Romania must be designed
on the basis of the new economic context and emerging psychoactive substance use. Hence, women who use drugs should benefit
from a wider access to medical and social services.
References
1. Compartment for Monitoring and Evaluation of HIV/AIDS Data in
Romania.
2. Märdärescu M. Paediatrics in Romania 2013. JUSTRI Meeting 67
September 2013, Bucharest.
3. Miralles M, Mädärescu L, Sherr. What do we know about the
situation of women living with HIV in Europe? Antiviral Therapy
2013; 18 Suppl 2:1114.
4. Märdärescu M, Branco T. East meets West: Management of
Women Living with HIV/AIDS. European AIDS Conference 2011.
Belgrade.
ART management in children perinatally infected with HIV
from mothers who experience behavioural changes in
Romania
1
1
1
Mariana Märdärescu ; Alina Cibea ; Cristina Petre ;
Ruxandra Neagu-Drãghicenoiu1; Rodica Ungurianu1;
Sorin Petrea1; Ana Maria Tudor1; Delia Vlad1; Carina Matei1 and
Mãrdãrescu Alexandra2
1
Paediatric Immunodepression Department, Prof. Dr. Matei Bal,
National Institute for Infectious Diseases, Bucharest, Romania.
2
Romanian HIV/AIDS Centre, ‘‘Prof. Dr. Matei Bal’’, National Institute
for Infectious Diseases, Bucharest, Romania.
Introduction: During the recent years the rate of HIV perinatally
exposed children in Romania has increased as a consequence of
the expanding number of HIV-infected women. These women belong
to Romania’s long-terms survivors, aged between 20 and 24 years
and to the group of new HIV infection cases (2024 years), acquired through unsafe sexual contact and use of new psychoactive
substance (IV).
Materials and Methods: We focused on 396 HIV perinatally exposed
children born between 2008 and 2013, under surveillance in National
Institute for Infectious Diseases ‘‘Prof. Dr. Matei Bals,’’ Bucharest. Of
them, 43 acquired HIV through materno-foetal transmission. Our aim
was to observe the characteristics in their evolution under antiretroviral treatment and to emphasize the causes of treatment failure.
Children with perinatally acquired HIV infection were followed in a
retrospective case series. We assessed maternal characteristics, HIV
vertical transmission prophylaxis, timing of diagnosis, immunological
and virologic status and features of the evolution under combined
antiretroviral therapy (cART).
Results: The rate of mother-to-child HIV transmission was 10.8%
versus the national rate registered in 2013, namely B5%. 16% of
mothers belonged to the Romanian 1990s cohort and 84% were
recently infected with HIV, through unprotected sexual contact (70%)
or use of new psychoactive substances (14%). 51% of mothers were
diagnosed postnatally as a consequence of their reluctance to access
specific health services and in 57% CD4 value was B350 cell/mm.
41% of the monitored children were diagnosed with HIV infection at
birth. Their median entry CD4 value was 23% and 49% had a CD4
25%; median entry viral load was 7 log. 16 patients (37%) had
undetectable viral load after six months of treatment. In 87.5% of
them the virologic suppression was achieved and maintained with
one single regimen (2 NRTIs1 NNRTI or 2 NRTIs1 PI/r). 15
children (35%) did not achieve suppression of viral load. 19 children
(44%) faced special issues related to adherence to antiretroviral
P169
Effectiveness of the prevention of mother-to-child
transmission of HIV protocol applied at Saint Camille
Medical Centre in Ouagadougou, Burkina Faso
Serge Theophile Soubeiga1; Cyrille Bisseye2; Rebecca Compaore1;
Elsa Assengone2; Djeneba Ouermi1; Florencia Djigma1; Tani Sagna1;
Virginio Pietra3 and Jacques Simpore1
1
Molecular Biology, University of Ouagadougou/CERBA/LABIOGENE,
Ouagadougou, Burkina Faso. 2Faculty of Sciences, Department of
Biology, University of Sciences and Technology of Masuku,
Franceville, Gabon. 3Biology, University of Brescia, Brescia,
Italy.
Introduction: Despite many prevention efforts, the number of
children infected by HIV in sub-Saharan Africa through vertical
transmission remains high. This infection can be reduced through
programmes of prevention of mother-to-child HIV transmission
(PMTCT). The objective of this study was to evaluate the effectiveness of the PMTCT protocol at Saint Camille Medical Centre in
Ouagadougou, Burkina Faso.
Methods: From August 2012 to September 2013, samples of dried
blood spot (DBS) were collected from 160 children aged 6 weeks
born to HIV-1 positive mothers who were under PMTCT protocol at
Saint Camille Medical Centre and 40 children of the same age group
from orphanages and whose mothers were dead or unknown. The
samples were tested using the Abbott Real Time HIV-1 Qualitative
kit. The clinical data of mothers were collected and analyzed using
SPSS Version 17.0 and Epi Info Version 6.0 softwares.
Results: Among pregnant women in this study, 52.5% were predominantly young (2429 years) and 60.62% were housewives. In total,
50.5% (101/200) were in combination of AZT/3TC/NVP and 29.5%
(59/200) were on prophylaxis (AZT/3TC). The rate of vertical transmission of HIV-1 was 0.0% (p B0.001) in children whose mothers
were taking a combination of AZT/3TC/NVP (0/101) or were on a
prophylaxis AZT/3TC treatment (0 /59). The rate of HIV-1 transmission in orphaned children was 15.0% (6/40).
Conclusion: The PMTCT protocol is effective and reduces very
significantly (p B0.001) the risk of transmission of HIV-1 from
mother to child. In addition, screening by PCR of orphaned children
vertically infected with HIV, enabled them to receive an early
treatment.
133
P170
Possible association between the stage of HIV
disease, antiretroviral treatment and the nutrient
composition of breast milk in the Mangaung area,
South Africa
Wilhelmina van den Heever1; Geta de Wet2 and Moira Hattingh2
1
Health Sciences, Central University of Technology, Free State,
Bloemfontein, South Africa. 2Haematology, Pathcare Reference
Laboratory, Bloemfontein, South Africa.
Introduction: In South Africa where replacement feeding may not be
affordable, feasible or sustainable, HIV-infected women are recommended to exclusively breastfeed their infants during the first six
months of life. The question arises whether HIV disease progression
and its metabolic impact on the mother will affect the nutrient
composition of breast milk. The aim was to determine the possible association between HIV disease progression, as measured by
the immunological markers, and the nutrient composition of breast
milk.
Methods: The nutrient composition of breast milk of 100 HIVinfected and 50 non-infected volunteered (control group) lodging/
day visiting mothers at Paediatric/Neonatal wards of National,
Pelonomi and Universitas hospitals, Bloemfontein, were measured.
The HIV-infected group was subdivided into HIV-naı̈ve and HIV-ARV
treatment group. Breast milk and blood samples were obtained.
Macronutrients namely lactose, proteins, fat, total solids and the
energy content of the breast milk and micronutrient namely calcium
and phosphate were measured. Blood and immunological parameters comprised of CD4/CD8T cell counts, viral loads and full
blood counts.
Results: Protein levels amongst the HIV-infected group showed a
significant elevation (p B0.0001) compared to the control group. The
calcium levels of the HIV-infected group were significantly lower
(p 0.0081) than the control group. No statistically significant
differences were recorded of the measured nutrients between
mothers receiving treatment and the HIV-naı̈ve group. All the HIV
patients were anaemic with haemoglobin, haematocrit and RDW
below the normal range. The Spearman Correlation Coefficient was
used to determine if HIV disease progression have an influence on
the nutrient composition. For the HIV-naı̈ve group, a significant
correlation was found between the viral load and percentage total
solids in breast milk. A correlation between the CD4T cell count,
the percentage total solids and energy content of the breast milk was
determined in the HIV-ARV treatment group. No strong positive
correlation could be established between the immunological markers, HIV disease progression and the nutrient composition in the
breast milk.
Conclusions: HIV mothers can breastfeed their babies even at a more
advanced stage of HIV disease progression, but emphasis has been
placed on exclusive breastfeeding.
P171
The spectrum of HIV mother-to-child transmission risk
Veronique Reliquet1; Norbert Winer2; Natacha Chereau3;
Elise Launay3; Aurore Lamberet3; Elisabeth Andre-Garnier4;
Francois Raf1 and Cecile Brunet1
1
Infectious Diseases, CHU Nantes, Nantes, France. 2Obstetrics and
Perinatal Medicine, CHU Nantes, Nantes, France. 3Pediatrics, Hôpital
Mère-Enfant, CHU Nantes, Nantes, France. 4CHU Nantes, Virology
Laboratory, Nantes, France.
Introduction: With the implementation of combined antiretroviral therapy (cART) and prevention of mother-to-child transmission
Poster Abstracts
(MTCT) we observed dramatic decreases in rates of perinatal MTCT
of HIV, 0.3% in France in women with plasma viral load (pVL) B50
c/mL at delivery. We describe a case of MTCT which occurred despite
virologic suppression of the mother at delivery, the first case in our
centre since 2002.
Description of the case: A 26-year-old black woman, Guinea-native,
living in France since 2007, was diagnosed with HIV-1 CRF02 in 2008
and lost to follow-up since November 2012 after second delivery
(2 female born in March 2009 and October 2012, uninfected). Third
pregnancy began in July 2013 and baseline characteristics in
September were as follows: week 13 of gestational age (GA), CDC
stage A, CD4 317/mm3, pVL 4.89 log c/mL. cART with abacavir/
lamivudine and atazanavir/ritonavir 300/100 mg daily (qd) was
introduced. VL decreased to 2.4 log c/mL in 4 weeks and CD4
increased to 456/mm3. In December, at week 22 of GA, viral rebound
at 4.14 log c/mL due to sub-optimal maternal adherence was
observed. After counselling, pVL decreased to 1.69 log c/mL in March
2014, at week 35 of GA and 1.3 log c/mL at delivery. As pVL was
B400 c/mL at week 36 of GA, vaginal delivery with IV zidovudine
was decided. However, because of poor/uncertain maternal adherence
to cART, the neonate was treated with a combination of 2 drugs
(lamivudine-nevirapine) with the 4-week zidovudine regimen, until
the result of delivery pVL. This combination was stopped at day 2
when maternal delivery pVL (22 c/mL) was received and standard
oral zidovudine prophylaxis was continued. Infant was tested for HIV
infection at baseline (day 3) and found to be HIV-infected (HIV-RNA
60 c/mL) attesting in-utero HIV transmission. On day 15, zidovudine
prophylaxis was discontinued and treatment for HIV infection
initiated with standard cART according to the French Paediatric
Antiretroviral Guidelines.
Conclusions: The risk of HIV acquisition is low in infants born to
women who receive standard cART during pregnancy and labour and
achieve undetectable VL at delivery. However, transmission remains
a hazard, with possibility of in-utero infection during episodes of
non-adherence, and the risk of a possible MTCT has to be mentioned
to all pregnant women.
P172
Transmitted drug resistance in women with intrapartum
HIV-1 diagnosis: a pilot epidemiological survey in Buenos
Aires, Argentina
Diego Cecchini1; Ines Zapiola2; Silvina Fernandez Giuliano2;
Marina Martinez3; Claudia Rodriguez1 and Maria Belen Bouzas2
1
Infectious Diseases Unit, Hospital Cosme Argerich, Buenos Aires,
Argentina. 2Virology Unit, Hospital Francisco Muñiz, Buenos Aires,
Argentina. 3Neonatology Unit, Hospital Cosme Argerich, Buenos
Aires, Argentina.
Introduction: Surveillance of primary resistance to antiretroviral
drugs is particularly important in pregnant population, in which
infection by drug-resistant HIV has not only implications for maternal
treatment, but could also jeopardize the efficacy of neonatal
prophylaxis. We aim to describe the prevalence of resistance associated mutations (RAMs) in pregnant women with intrapartum HIV
diagnosis in a public hospital of Buenos Aires, Argentina.
Materials and Methods: Prospective pilot study (period from 2008
to October 2013). Plasma samples were tested for viral load by
Versant HIV-1 RNA 3.0 (bDNA) and sequenced using HIV-1 TRUGENETM
Genotyping Kit (Siemens). The prevalence of RAMs was analyzed
according to World Health Organization (WHO) criteria.
Results: Of 231 HIV-infected pregnant women assisted, 6% (n14)
had intrapartum diagnosis of HIV infection. 12 patients (85.7%) had
previous pregnancies, 10 (71.4%) had inadequate prenatal care and
134
3 (23.1%) seroconverted during pregnancy. Maternal characteristics
(expressed medians and ranges) were: age 25.5 (1635) years;
gestational age at birth: 39 (3042) weeks; CD4 count: 500 (132
925) cells/mL; viral load: 9418 (180055299) copies/mL. No one had
hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfection; four
(33.3%) had syphilis. Eight patients (57.1%) had vaginal delivery and
six emergency C-section (42.9%). In six cases (46.2%), membrane
rupture was spontaneous; four patients (28.6%) failed to receive
intrapartum zidovudine (ZDV) infusion. In 12 patients a genotypic
resistance test was performed: two (16.7%) had WHO RAMs
corresponding to K103N mutation in both cases, conferring highlevel resistance to nevirapine (NVP) and efavirenz. Two newborns
(14.3%) were preterm. All received neonatal prophylaxis: ZDV in 1
case and combined prophylaxis (ZDV/3TC/NVP) in the remaining 13
(92.9%). All newborns were formula-fed. Two (14.3%) had congenital
syphilis, one of whom died. One newborn was HIV-infected (positive
proviral DNA at 24 hours of life, wild-type HIV).
Conclusions: This pilot study suggests that levels of transmitted
resistance in this high-risk population of pregnant women could
be moderate to high. We preliminarily observed high-level resistance
to NVP: if this finding is confirmed with a larger sample, it could
potentially jeopardize the utility of this drug in the combined
neonatal prophylaxis recommended in the absence of maternal
antiretroviral therapy.
References
1. Zapiola I, Cecchini D, Fernandez Giuliano S, Martinez M, Rodriguez
C, Bouzas MB, et al. The HIV Antiretroviral Resistance in PregnAncy
(HARPA) study: results of a two year surveillance of drug resistance
associated mutations in HIV-infected pregnant women in Buenos
Aires, Argentina. Book of abstracts, MOPE152, 6th IAS Conference on
HIV Pathogenesis, Treatment and Prevention, Rome, 1720 July 2011.
2. Bennett DE, Camacho RJ, Otelea D, Kuritzkes DR, Fleury H, Kiuchi
M, et al. Drug Resistance Mutations for Surveillance of Transmitted
HIV-1 Drug-Resistance: 2009 Update. PLoS ONE. 2009;4(3):e4724.
P173
Prevention of mother-to-child transmission: experience of a
Portuguese centre
Carmela Piñeiro1; Soa Fernandes2; Cristóvão Figueiredo1;
Ana Soa Santos1; Marina Moucho2; Rosário Serrão1;
Nuno Montenegro2 and António Sarmento1
1
Infectious Diseases Service, Centro Hospitalar São João, Porto,
Portugal. 2Obstetrics and Gynaecology Service, Centro Hospitalar São
João, Porto, Portugal.
Introduction: HIV infection during pregnancy still raises controversial
issues. Combined antiretroviral therapy (cART) has been successful in
reducing mother-to-child transmission (MTCT). Routine screening in
pregnancy and in pre-conception consultation proved to be one of
the best methods able to get this treatment on time. We review our
experience with pregnant patients with HIV infection.
Materials and Methods: Retrospective and descriptive study. Data
obtained from HIV-infected pregnant women from 1999 to 2012
with delivery and subsequent infectious diseases follow-up at our
hospital.
Results: We evaluated 136 patients (169 pregnancies), with a total
of 147 living newborns (2 twin pregnancies) and 1 stillbirth. Median
age at pregnancy was 30 (SD 5.7) years. Four patients were HIV-2
infected and one HIV-12 infected. 26 (19.1%) women were HCV coinfected and 6 (4.4%) HBV co-infected; 1 patient has HCV and HBV
co-infection. Sexual risk for HIV acquisition was determined in 102
(75%) patients and 31 (22.8%) were intravenous drug users. 33/136
Poster Abstracts
(24.2%) women were diagnosed on routine screening in pregnancy, 4
during delivery and 2 immediately after delivery. 36 (26.4%) patients
had an AIDS-defining entity before pregnancy and no new opportunistic infections were diagnosed. ART was used in 157 (92.9%)
pregnancies and 15 (9.5%) of them were treated only with NRTIs. At
the time of delivery 86/144 (59.7%) patients had undetectable viral
load (VL) (25 patients without VL determined), 91.7% of those on
ART. 119 (70.4%) had a TCD4 cell count above 200 cells/mm3. MTCT
occurred in 3/147 cases (2%): in one mother HIV-1 infection was
diagnosed three weeks before delivery, other immediately after delivery and the third woman started cART (2NRTI1PI/r) in the second
trimester of pregnancy, always adherent and without secondary
effects, VL at delivery was 50 copies/mL and elective C-section was
performed.
Conclusions: The fact that 24% of patients were diagnosed during
pregnancy shows the importance of routine screening to all pregnant women. MTCT occurred in three children, but only one was
administered cART for prevention.
NEW TREATMENT AND TARGETS
P174
Universal Tre (uTre) recombinase specifically targets the
majority of HIV-1 isolates
Janet Karpinski1; Jan Chemnitz2; Ilona Hauber2; Josephine AbiGhanem3; Maciej Paszkowski-Rogacz1; Vineeth Surendranath4;
Debojyoti Chakrabort1; Karl Hackmann5; Evelin Schröck5;
Marı́a Teresa Pisabarro3; Joachim Hauber2 and Frank Buchholz1
1
Medical Systems Biology, Medical Faculty, TU Dresden, Dresden,
Germany. 2Antiviral Strategies, Heinrich Pette Institute Leibniz
Institute for Experimental Virology, Hamburg, Germany. 3Structural
Bioinformatics, TU Dresden, Dresden, Germany. 4Molecular Cell
Biology and Genetics, Max Planck Institute, Dresden, Germany.
5
Clinical Genetics, Medical Faculty, TU Dresden, Dresden, Germany.
Current drugs against HIV can suppress the progression to AIDS but
cannot clear the patient from the virus. Because of potential side
effects of these drugs and the possible development of drug
resistance, finding a cure for HIV infection remains a high priority
of HIV/AIDS research. We recently generated a recombinase (termed
Tre) tailored to efficiently eradicate the provirus from the host
genome of HIV-1 infected cells by specifically targeting a sequence
that is present in the long terminal repeats (LTRs) of the viral DNA
[1]. In vivo analyses in HIV-infected humanized mice demonstrated
highly significant antiviral effects of Tre recombinase [2]. However,
the fact that Tre recognizes a particular HIV-1 subtype A strain may
limit its broad therapeutic application. To advance our Tre-based
strategy towards a universally efficient cure, we have engineered a
new, universal recombinase (uTre) applicable to the majority of HIV-1
infections by the various virus strains and subtypes. We employed
the search tool SeLOX [3] in order to find a well-conserved HIV-1
proviral sequence that could serve as target site for a universal Tre
from sequences compiled in the Los Alamos HIV Sequence Database.
We selected a candidate (termed loxLTRu) with a mean conservation
rate of 94% throughout the major HIV-1 subtype groups A, B and C.
We applied loxLTRu as substrate in our established substrate-linked
protein evolution (SLiPE) process [4] and evolved the uTre recombinase in 142 evolution cycles. Highly specific enzymatic activity on
loxLTRu is demonstrated for uTre in both Escherichia coli and human
cells. Naturally occurring viral variants with single mutations within
the loxLTRu sequence are also shown to be efficiently targeted by
uTre, further increasing the range of applicability of the recombinase.
135
Potential off-target sites in the human genome are not recombined
by uTre. Furthermore, uTre expression in primary human T cells
shows no obvious Tre-related cytopathic or genotoxic effects. Finally,
uTre expressing mice show no undesired phenotypes during their
normal lifespan. We have developed a broad-range HIV-1 LTR specific recombinase that has the potential to be effective against the
vast majority of HIV-1 strains and to cure HIV-1 infected cells from
the infection. These results strongly encouraged us in our confidence
that a Tre recombinase-mediated HIV eradication strategy may
become a valuable component of a future therapy for HIV-infected
patients.
References
1. Sarkar I, Hauber I, Hauber J, Buchholz F. HIV-1 proviral DNA
excision using an evolved recombinase. Science. 2007;316(5833):
19125.
2. Hauber I, Hofmann-Sieber H, Chemnitz J, et al. Highly Significant
Antiviral Activity of HIV-1 LTR-Specific Tre-Recombinase in Humanized Mice. PLoS pathogens. 2013;9(9):e1003587.
3. Surendranath V, Chusainow J, Hauber J et al. SeLOX–a locus of
recombination site search tool for the detection and directed evolution of site-specific recombination systems. Nucleic acids research.
2010;38(Web Server issue):W2938.
4. Buchholz F, Stewart AF. Alteration of Cre recombinase site specificity by substrate-linked protein evolution. Nature biotechnology.
2001;19(11):104752.
P175
Targeted destruction of HIV-positive cells
Jyoti R Sharma1; Cleo Dodgen1; Amanda Skepu2 and Mervin Meyer1
1
Biotechnology, University of Western Cape, Bellville, Cape Town,
South Africa. 2Nanotechnology Innovation Centre, Mintek, Randburg,
South Africa.
Introduction: HIV/AIDS is now a global epidemic that has become the
leading infectious killer of adults worldwide. Although antiretroviral
(ARV) therapy has dramatically improved the quality of life and
increased the life expectancy of those infected with HIV but frequency of dosing and drug toxicity as well as the development of
viral resistance pose additional limitations. The rapidly expanding
field of nanotechnology has vast potential to radically advance the
treatment and prevention of HIV/AIDS. Nanoparticles can provide
improved drug delivery, by virtue of their small size, robustness,
safety, multimodality or multifunctionality.
Aims and objectives: Since HIV primarily infects CD4 cells; we aim
to use CD4 as a selectable target to deliver a pro-apoptotic protein
to HIV-infected cells using nanoparticles as carriers. The aim of study
was to develop a nanotechnology-based death inducing delivery
system for the destruction of CD4HIV infected cells through the
activation of caspase-3.
Methodology: A modified caspase-3 protein (Mut-3) was engineered, which is cleavable only by HIV-1 protease. Mut-3 can activate
apoptosis in the presence of HIV-1 protease, consequently killing
HIV-positive cells. Mut-3 protein was conjugated to gold nanoparticles together with a CD4-targeting peptide. The efficacy of the
gold nanoparticles was tested on CHO cells that were genetically
engineered to express GFP labelled CD4 and HIV-1 protease.
Results: Mut-3 was expressed in bacterial cells and purified. CHO
cells that stably over express CD4-GFP and HIV-1 protease were
selected using Fluorescence Activated Cell Sorting. Dose response
cell culture experiments showed that gold nanoparticles without
Mut-3 and CD4-targeting peptide did not induce cell death in CHO
cells, while gold nanoparticles that was conjugated with Mut-3
Poster Abstracts
and the CD4-targeting peptide rapidly induced cell death in CHO
cells.
Conclusions: Our results suggest that gold nanoparticles conjugated
with Mut-3 and a CD4-targeting peptide could potentially induce
apoptosis in HIV-infected cells.
NON-AIDS MORBIDITIES
MORTALITY, AND AGEING
AND
P177
CD4/CD8 ratio is not predictive of multi-morbidity
prevalence in HIV-infected patients but identify patients
with higher CVD risk
Marianna Menozzi; Stefano Zona; Antonella Santoro; Federica Carli;
Chiara Stentarelli; Cristina Mussini and Giovanni Guaraldi
Infectious Disease Clinic, AOU Policlinico di Modena, Modena, Italy.
Background: CD4/CD8 B0.8 is a surrogate marker of immuneactivation/immunosenescence and independently predicts mortality
in the HIV-infected patients due to non-AIDS related events. Most
studies showed that patients on antiretroviral therapy (ART) often
fail to normalize the CD4/CD8 ratio despite CD4 count normalization.
Primary objective of the study was to explore the impact of CD4/
CD8B0.8 as independent predictor of HIV-associated non-AIDS
(HANA) conditions and multimorbidity (MM) in HIV patients. In
patients with no previous history of cardiovascular disease (CVD) a
particular insight is provided in the association between impact of
CD4/CD8 B0.8 and risk prediction of CVD or radiological markers of
subclinical CVD.
Material and Methods: 914 consecutive patients attending Modena
Metabolic HIV Clinic were evaluated in a cross-sectional retrospective
study. Inclusion criteria: stable ART from ]2 years; HIV-RNA plasma
levels B40 copies/mL; stable CD4 count ]350/mmc. CD4/CD8 strata
(0.8) was chosen as a cut off representing the median value of the
cohort. MM was defined as the presence of ]2 HANA conditions
including standard defined: chronic kidney disease, hypertension,
previous CVD events, osteoporosis and diabetes mellitus. Calendar
year of ART initiation was defined: ‘‘PreART’’ ( B2000); ‘‘EarlyART’’
(20002005) and ‘‘LateART’’ ( 2006). High CVD risk was defined
for Framingham Risk Score (FRS)]6. Subclinical CVD was defined
using cardiac CT scan for calcium score (CAC) ]100. Logistic univariate
strata.
HANA distribution across CD4/CD8
136
Poster Abstracts
Patients demographic, anthropometric and HIV specific characteristics
MM MM
Total Number
665 (72.5%)
249 (27.5%)
Women
200 (30.1%)
48 (19.3%)
0.001
47 (44-51)
52 (48-58)
B0.001
147 (23.5%)
72 (29.5%)
Age
CDC C stage
Smoking status
P value
0.037
0.001
Non-smoker
376 (57.5%)
171 (69%)
B10 cigarettes/day
10 cigarettes/day
105 (16.1%)
173 (26.5%)
40 (16.1%)
37 (14.9%)
Sedentary life
376 (57.5%)
171 (69%)
0.351
No alcohol intake
349 (53.4%)
160 (34.5%)
0.002
BMI
23 (2125)
24 (21-26)
0.010
Fasting glucose
91 (8698)
99 (89114
B0.001
Triglycerides
139 (98199)
164 (111220)
0.028
Total Cholesterol
199 (171227)
196 (169222)
0.481
HDL Cholesterol
HIV duration (months)
47 (3857)
213 (149300)
45 (36.53)
217 (174273)
0.014
0.017
CD4 nadir
210 (104300)
172 71-284)
0.022
Current CD4
652 (508814)
628 (483803)
0.538
Current CD8
867 (6501127)
890 (6291200)
0.068
Current CD4/CD8 ratio
0.76 (0.571.03)
0.76 (0.511.09)
0.489
B0.8
373 (56.1%)
136 (54.6%)
0.8
ARV initiation
292 (43.9%)
113 (45.5%)
PreART
383 (58.1%)
157 (63.1%)
EarlyART
168 (25.5%)
67 (26.9%)
LateART
108 (16.4%)
25 (10%)
36 (-7)
41 (-9)
CD4/CD8 ratio strata
Age at ARV initiation
0.373
0.049
and multivariable adjusted analysis were performed to assess
relationships between variables.
Results: Demographic and HIV-specific variables distribution in
patients with and without MM are shown in Table 1.
Figure 1 shows HANA distribution across CD4/CD8 strata: CVD prevalence only appeared to be higher in patients with no CD4/CD80.8.
In multivariable analyses CD4/CD8B0.8 was not an independent predictor of MM (OR1.225, CI 0.891; 1.681, p0.211) after adjustment
for age, gender and BMI. Patients with CD4/CD8B0.8 displayed higher
CVD risk but not higher prevalence of subclinical CVD. At multivariable
analyses CD4/CD8B0.8 remained predictor of higher CVD risk
(OR0.65, CI 0.470.917, p0.014) after correction for sex, BMI,
age strata and HIV infection duration.
Conclusions: Low CD4/CD8 ratio was not associated with MM prevalence. Patients with CD4/CD8 B0.8 ratio displayed higher prevalence of CVD. At multivariable logistic regression CD4/CD8 B0.8 is
an independent prepredictor of enhanced CVD risk. This may support role of immune-activation/senescence in the pathogenesis of
CVD.
P178
Viro-immunological characterization of naı̈ve patients with
high cerebrospinal fluid (CSF) HIV RNA
0.001
Francesca Iannuzzi; Francesca Bai; Esther Merlini; Mattia Truno;
Lidia Borghi; Teresa Bini; Antonella d’Arminio Monforte and
Giulia Marchetti Carla
Clinical of Infectious Disease, San Paolo Hospital, University of Milan,
Milan, Italy.
Background: HIV can spread into the central nervous system (CNS)
early in the course of infection and this turns into intrathecal
inflammation and neuronal damage. We aimed to investigate clinical
and immunological parameters associated with elevated CSF VL in
HIV-infected ART-naı̈ve patients.
Material and Methods: HIV ART-naı̈ve patients underwent a comprehensive battery of neurocognitive (NC) tests and lumbar puncture
(LP) for CSF HIV-RNA detection. Plasma HIV-RNA and peripheral
T-cell immune-phenotypes (CD38/CD45RA/CD45R0/CD127 on CD4/
CD8) were also assessed (flow cytometry). High-CSF HIV RNA was
defined as ]10000cp/mL (H-CSF), while CSF HIV RNA B10000cp/mL
characterized low VL patients (L-CSF). Chi-square and Mann-Whitney
tests were used. Parameters independently associated with CSF VL
were explored by multivariate regression.
Results: A total of 131 patients were retrospectively enrolled. Fortytwo patients (32%) had CSF VL 10000 cp/mL.
Table 1 shows the features of H- versus L-CSF patients. Compared to
L-CSF patients, H-CSF patients displayed lower current CD4%, lower
CD4/CD8 ratio and higher CD8%. No differences in NC tests performance were observed between groups (p 0.6). Regarding T-cell
137
Poster Abstracts
Abstract P178Table 1. Demographic and immune-virological characteristics of the study population and comparison between
H-CSF and L-CSF patients
Female, n (%)*
Age (years), median (IQR)*
Time since first HIV diagnosis (months), median (IQR)*
Plasma HIV-RNA, Log cp/mL median (IQR)*
CSF-HIV-RNA, Log cp/mL median (IQR)*
CD4 T-cell, cell/mmc median (IQR)
CD4 T-cell, % median (IQR)
CD8 T-cell, cell/mmc, median (IQR)
CD8 T-cell, % median (IQR)
Nadir CD4 t-cell, cell/mmc median (IQR)*
Ratio CD4/CD8, median (IQR)*
Symptomatic for headache, n (%)
HCV co-infection, n (%)*
HBC co-infection, n (%)*
Altered neurocognitive tests**, n (%)
T-cell Activation
CD38CD8%, median (IQR)*
CD45R0CD38CD8%, median (IQR)*
T-cell Maturation/Differentiation
CD4SRACD4%, median (IQR)*
CD45RACD8%, median (IQR)*
CD45R0CD8%, median (IQR)*
CSF-HIV-RNA
CSF-HIV_RNA
B10000 cp/mL
10000 cp/mL
Tot naı̈ve n 131
(L-CSF pts) (n89)
(H-CSF pts) (n 42)
P value
12 (9)
38 (3245)
3.7 (121)
4.89 (4.225.42)
3.65 (3.044.19)
307 (150417)
19 (1124)
921 (6501172)
57 (5166)
282 (130388)
0.33 (0.170.45)
14 (11)
7/112 (6)
8/98 (8)
25/53 (47)
6 (6)
38 (3245)
4.4 (1.315.9)
4.69 (4.165.26)
3.44 (2.893.67)
320 (154446)
20 (1225)
901 (6501092)
55 (4962)
305 (131405)
0.37 (0.20.48)
4 (5)
5/76 (6)
6/64 (9)
18/40 (45)
6 (16)
38 (3249)
3 (133)
5.23 (4.785.85)
4.76 (4.225.09)
267 (125366)
17 (1020)
1037 (6521222)
62 (5373)
209 (125357)
0.28 (0.140.37)
10 (24)
2/36 (5)
2/34 (6)
7/13 (54)
0.162
0.886
0.718
0.002
0.0001
0.076
0.028
0.207
0.005
0.157
0.021
0.001
0.834
0.548
0.579
13 (723)
8 (416)
12 (621)
7 (414)
17 (826)
11 (618(
0.074
0.017
11 (615)
26 (2134)
7 (310)
17 (1323)
20 (1629)
11 (716)
26 (2133)
7 (410)
20 (1424)
20 (1529)
9 (513)
25 (2135)
6 (38)
16 (1019)
25 (1632)
0.059
0.656
0.250
0.007
0.163
H-CSF, patients with CSF HIV-RNA ]10.000 cp/mL; L-CSF, patients with CSF HIV-RNAB10.000 cp/mL.
immuno-phenotypes, H-CSF patients displayed a higher proportion of
CD45R0CD38CD8 (11 vs 7%, p0.02) and lower expression of
CD45RACD8 % (16 vs 20%, p0.007), in comparison to L-CSF
patients. In multivariate analysis CD45RACD8 T-cells % (OR 0.917,
CI 95% 0.8520.987, p0.002) was associated with H-CSF, even after
adjustment for plasma VL, CD8 and CD4 count. Globally, in univariate
CSF VL inversely correlated with CD45RACD8 % (r 0.223,
p0.0217) and CD127CD4 % (r 0.204, p 0.0225), while a
positive association was found between CSF and plasma VL (r0.303,
p0.0004) and CD8 % (r0.211, p 0.016). In multivariate linear
regression, in addition to positive association between plasma and
CSF VL (b: 0.212, 95% CI 0.020.41, p 0.032), also CD45RACD8
% were confirmed inversely associated to CSF VL (b: 0.21, 95% CI
0.5 to 0.002, p0.036), adjusting for CD4/CD8 and CD4CD127 %.
Conclusions: We hereby describe a 32% prevalence of H-CSF in a
cohort of HIV ART-naı̈ve patients. Subjects with high-CSF viral replication are mostly with higher systemic immune activation, in particular the percentage of naı̈ve CD8 T-cell is positively associated with
CSF VL, irrespective of plasma VL. In HIV ART-naı̈ve patients,
especially if featuring a hyperactivated T-cell immune-phenotype,
lumbar puncture should be considered to further guide CNS-targeted
cART.
P179
Overall and cause-specific mortality in HIV-positive subjects
compared to the general population
Belen Alejos1; Victoria Hernando1; Jose López-Aldeguer2;
Ferrán Segura3; José Antonio Oteo4; Rafael Rubio5;
Arantza Sanvisens6; Paz Sobrino1; Julia del Amo1 and Cohort Coris7
1
National Center of Epidemiology, Institute of Health Carlos III,
Madrid, Spain. 2CoRIS cohort, Hospital La Fe, Valencia, Spain. 3CoRIS
cohort, Hospital Parc Tauli, Sabadell, Spain. 4CoRIS cohort, Hospital
San Pedro, Logroño, Spain. 5CoRIS cohort, Hospital Doce de Octubre,
Madrid, Spain. 6CoRIS cohort, Germans Trias i Pujol, Badalona, Spain.
7
CoRIS cohort, Institute of Health Carlos III, Madrid, Spain.
Introduction: Emerging non-AIDS related causes of death have been
observed in HIV-positive subjects in industrialized countries. We
aimed to analyze overall and cause-specific excess of mortality of
HIV-positive patients compared to the general population and to
assess the effect of prognostic factors.
Material and Methods: We used generalized linear models with
Poisson error structure to estimate overall and cause-specific excess
of mortality in HIV-positive patients from 2004 to 2012 in the cohort
of the Spanish Network of HIV Research (CoRIS), compared to
Spanish general population and to assess the impact of multiple risk
factors. We investigated differences between short-term and longterm risk factors effects on excess of mortality. Multiple Imputation
by Chained Equations was used to deal with missing data.
Results: In 9162 patients there were 363 deaths, 16.0% were nonAIDS malignancies, 10.5% liver and 0.3% cardiovascular related.
Excess mortality was 1.20 deaths per 100 person years (py) for allcause mortality, 0.16 for liver, 0.10 for non-AIDS malignancies and
0.03 for cardiovascular. Short-term (first-year follow-up) excess
Hazard Ratio (eHR) for global mortality for baseline AIDS was 4.27
138
(95% CI 3.066.01) and 1.47 (95% CI 0.952.27) for HCV coinfection;
long-term (subsequent follow-up) eHR for baseline AIDS was
0.88 (95% CI 0.581.35) and 4.48 (95% CI 2.717.42) for HCV
coinfection. Lower CD4 count and higher viral load at entry, lower
education, being male and over 50 years were predictors for overall
excess mortality. Excess of liver mortality was higher in patients with
CD4 counts at entry below 200 cells compared to those above
350 (eHR: 6.49, 95% CI 1.2134.84) and in HCV-coinfected patients
(eHR: 3.85, 95% CI 0.85 17.37), although it was borderline
significant. Patients over 50 years old (eHR: 5.55, 95%CI 2.412.85)
and HCV coinfected (eHR: 5.81, 95% CI 2.613) showed a higher risk
of non-AIDS malignancies mortality excess. Excess of cardiovascular
mortality was related with HCV coinfection (eHR: 6.68, 95% CI 1.25
35.73).
Conclusions: Our results show overall, liver, non-AIDS malignancies
and cardiovascular excess of mortality associated with being HIVpositive, despite improvements in HIV disease management and
antiretroviral therapies. Differential short-term and long-term
effect of AIDS before entry and HCV coinfection was found for overall
mortality.
P180
A comparison of inpatient admissions in 2012 from two
European countries
Victoria Tittle1; Giovanni Cenderello2; Ambra Pasa3; Preya Patel1;
Stefania Artioli4; Chiara Dentone5; Paolo Fraccaro6;
Mauro Giacomini7; Maurizio Setti8; Antonio Di Biagio9 and
Mark Nelson1
1
HIV Unit, Chelsea and Westminster Hospital, London, UK. 2Infectious
Diseases Unit, EO Ospedali Galliera, Genoa, Italy. 3IT Department,
EO Ospedali Galliera, Genoa, Italy. 4Infectious Diseases Unit,
ASL-5 La Spezia, La Spezia, Italy. 5Infectious Diseases Unit,
ASL-1 Imperiese, Sanremo, Italy. 6Centre for Health Informatics,
University of Manchester, Manchester, UK. 7Biomedics Engineering,
University of Genoa, Genoa, Italy. 8Immunology Unit,
San Martino Hospital/University of Genoa, Genoa, Italy. 9Infectious
Diseases Unit, San Martino Hospital/University of Genoa, Genoa,
Italy.
Poster Abstracts
Introduction: This study compares the trends of HIV inpatient
admissions between a London tertiary HIV centre (United Kingdom)
and four infectious disease wards in Italy (IT) to recognize common
patterns across Europe.
Methods: Data regarding HIV inpatient admissions was collected by
using discharge diagnostic codes from 1 January to 31 December
2012, including patient demographics, combined antiretroviral
therapy (cART) history, CD4, viral load (VL) and mortality rates.
Discharge diagnoses were categorized according to the International
Classification of Disease (ICD) 9 and 10 system. All ICD categories
that reach a 3% threshold of total admissions were analyzed.
Results: A total of 731 admissions (257 in Italy and 474 in the United
Kingdom) for 521 patients (1.5 mean admission per patient). Female
admissions were higher in Italy at 22.6% (n 58) compared to 14.9%
(n 47) in the United Kingdom. Median age of patients was 47 years
old. There was an undetectable VL in 65.8% (n 169) of admissions
in Italy and 67.1% (n 319) in the United Kingdom (p 0.385);
86.4% (n 222) and 82.4% (n 389) of admissions were on cART,
respectively. Mean CD4 was 302 in Italy compared to 368 in the
United Kingdom (p 0.003). Average length of admission was
16 days with a 10.2% (n 21) mortality rate in Italy compared to
8 days with 2.8% (n 9) mortality in the United Kingdom (p B0.001).
HCV co-infection was present in 64.6% (n 166) in Italy and
13.5% (n 64) in the United Kingdom and commonest mode of
transmission was needle use in Italy (67.3%, n 173) and men who
have sex with men in the UK cohort (59.9%, n284). The cause of
inpatient admissions according to ICD codes can be seen in following
Figure 1.
Conclusions: Significant differences in the duration of inpatient
admission and mortality rates can be observed between these two
cohorts which is secondary to the impact of Hepatitis C co-infection
in Italy. However increases in the number of Hepatitis C co-infection
patients amongst MSM in London has been reported [1] and route
of transmission in Italy is shifting towards MSM [2], therefore
it is important to learn how HIV is developing and managed in a
global context to help plan future for services. The UK cohort
demonstrates a wider range of conditions necessitating admission,
and with an ageing HIV population, this is expected to increase in
the future, requiring general and specialist HIV physicians to work
closely together. The HIV-RNA threshold is 400 copies/mL to account
Abstract P180Figure 1. Primary diagnosis admissions according to ICD classification (%) in the two cohorts.
139
for blips according to British HIV Association (BHIVA) Guidelines
2012 [3].
Poster Abstracts
Abstract P181Table 1. CVD risk calculator comparison
Framingham
References
1. Giraudon I, Ruf M, Maguire H, Charlett A, Ncube F, Turner J, et al.
Increase in diagnosed newly acquired hepatitis C in HIV-positive men
who have sex with men across London and Brighton, 20022006: an
outbreak? Sex Transm Infect. 2008;84:1115.
2. Casari S, et al. Epidemiological and clinical characteristics and
behaviours of individuals with newly diagnosed HIV infection: a
multicentre study in north Italy. J Prev MedHyg. 2012;53:1904.
3. BHIVA. Treatment of HIV-1 positive adults with antiretroviral
therapy 2012. (updated Nov 2013). HIV Medicine (2014), 15 (Suppl 1),
185.
P181
The potential impact of new national guidance on primary
prevention of cardiovascular disease in people living with
HIV
Nadia Ahmed; Sarah Bradley; Patrick Pearson; Simon Edwards and
Laura Waters
HIV, Mortimer Market Centre, London, UK.
Introduction: Cardiovascular disease (CVD) is the leading cause of
death in England and Wales. As people living with HIV (PLWH) age,
proactive management of CVD risk factors is crucial. The longawaited draft guidelines for CVD from the National Institute of
Clinical Excellence (NICE) propose lipid modification (with statins)
and lifestyle modification for 4074 year olds with 10% (previously 20%) 10-year risk of CVD using QRISK2. We currently use
Framingham so compared 3 CVD risk calculators in our cohort and
analyzed the impact of a change in CVD threshold on the proportion
of our patients who would need intervention.
Materials and Methods: Framingham, QRISK2 and JBS3 cardiovascular risk calculators were compared in a group of randomly selected
patients. Then, to analyze the impact of a change in primary prevention threshold on our cohort, we interrogated a prospectively
collected database to identify all individuals who had a documented
Framingham risk assessment and applied the current/proposed thresholds accordingly. We performed the same analysis for the three
calculator subgroup (recalculating Framingham risk). Finally we
surveyed HIV services in England & Wales regarding their choice of
calculator.
Results: We compared the 3 CVD risk calculators in 100 patients, see
Table 1.
In terms of eligibility for primary prevention 20.9% (916/4383) had
documented Framingham risk assessment as part of routine care.
Using a 20% threshold, 8.8% (81/916) would require intervention,
increasing to 35.2% (322/916) with a threshold for intervention
of 10%. Restricting analysis to the 100 patients to whom we applied
all three calculators resulted in the following proportion requiring
intervention with a 20%/10% threshold, respectively: Framingham
28%/76%, QRISK2 20%/53%, JBS3 15%/42% (four patients were
excluded due to incomplete data).
Conclusions: Reducing the threshold for cardiovascular preventative
measures to 10% vastly increases the number of patients requiring
primary intervention, from two- to fourfold depending on risk calculator used. This may have significant implications, including cost,
drugdrug interactions and patient experience, that HIV physicians
and general practitioners will need to address, ideally in a coordinated and patient-focused manner.
QRISK2
JBS3
Low/ B10%
24
47
56
Medium/1020%
48
33
25
High/ 20%
28
20
15
P183
Association between abdominal aortic calcifications, bone
mineral density and vertebral fractures in a cohort of HIVpositive patients
Nathalie Iannotti1; Lidia Gazzola1; Alessia Savoldi1; Elisa Suardi1;
Viola Cogliandro1; Francesca Bai1; Alberto Magenta2; Mauro Peri2;
Teresa Bini1; Giulia Marchetti1 and Antonella d’Arminio Monforte1
1
San Paolo Hospital, Clinic of Infectious Diseases, Milan, Italy. 2San
Paolo Hospital, Department of Radiology, Milan, Italy.
Introduction: Evidence from HIV-negative cohorts suggests a link
between osteoporosis and cardiovascular disease. We evaluated the
presence and distribution of abdominal aortic calcifications (AAC)
and its correlation with bone mineral density (BMD) and vertebral
fractures (VF) in a cohort of HIV-positive patients.
Materials and Methods: In this cross-sectional study, 280 asymptomatic HIV-positive patients from the SPID (‘‘San Paolo’’ Infectious
Diseases) cohort were submitted to lateral spine X-ray and DXA. AAC
was identified using the AAC-8 score, which estimates the total
length of calcification of the anterior and posterior aortic walls in
front of vertebrae L1L4. Low BMD was defined by T-score or Z-score
B 1 at lumbar spine or femoral neck. VF were identified by
morph-metric analysis of X-ray and were defined by the ‘‘spine
deformity index’’ (SDI) ]1 according to semiquantitative method by
Genant. Associations between AAC, BMD and SDI were evaluated by
univariate and multivariate logistic regression models. The relationship between the grade of AAC and SDI was evaluated by Spearman’s
correlation.
Results: AAC ]1 was present in 65 patients (23.2%); of these 15
patients showed moderate/severe calcifications (AAC2). Low BMD
was found in 163 patients (58.2%) and VF (SDI ]1) in 47/274 patients
(17.1%). By univariate analysis, factors associated with AAC 1
were: age (for additional 10 years older HR 3.81 [IC95% 2.645.51],
pB0.0001) lower CD4 nadir (for additional 50 CD4 HR 0.89 [IC95%
0.820.97], p 0.01) AIDS-diagnosis (HR 2.13 [IC95 % 1.114.08],
p0.02) and being on HAART (HR 2.75 [IC95% 1.285.90],
p0.009). In multivariate analysis, only age (OR 2.62, IC95% 1.72
3.99, pB0.0001) resulted significantly associated with AAC ]1.
HIV population
Predictors of vertebral fracture in our
Predictors of Vertebral Fracture in
AHR of
our HIV population
SDI]1
IC 95%
p
AAC ]1
2.87
Low BMD
0.70
1.306.31 .008
0.331.51 .37
Increased bone turnover
Vitamin D deficiency ( B30)
1.87
1.67
0.844.75 .12
0.525.38 .38
Increased PTH levels ( 65)
0.66
0.281.50 .32
140
Poster Abstracts
Patients with AAC]1 had twofold increase in the risk of low BMD (HR
2.45 [IC95% 1.324.45], p0.004) and VF (SDI 1: HR 2.17
[IC95% 1.14.2], p 0.02) compared to patients without AAC. The
grade of AAC was directly correlated with the grade of SDI
(rho 0.16; p 0.008): AAC2 determines a sixfold increase in
the risk of VF (HR 6.44 [IC95% 2.2118.79], p0.0006). AAC ]1
predict VF independently from BMD, vitamin D status and bone
turnover marker (Table 1).
Conclusions: In our HIV population, AAC resulted a strong predictor
of both low BMD and VF, irrespective of factors involved in bone
formation. The grade of AAC was directly correlated with the grade
of VF.
References
1. Bolland MJ, Wang TK, van Pelt NC, Horne AM, Mason BH, Ames
RW, et al. Abdominal Aortic Calcification on Vertebral Morphometry
Images Predicts Incident Myocardial Infarction. J Bone Miner Res.
2010;25:50512.
2. El Maghraoui A, Rezqi A, Mounach A, et al. Relationship between
vertebral fracture prevalence and abdominal aortic calcification in
men. Rheumatology. 2012;51(9):171420.
3. El Maghraoui A, Rezqi A, Mounach A, et al. Vertebral fractures and
abdominal aortic calcification in postmenopausal women. A cohort
study. Bone. 2013;56:2139.
P184
Burden of subclinical heart and lung disease detected on
thoracic CT scans of HIV patients on HAART
time since interruption
Stefano Zona1; Antonella Santoro1; Giulia Besutti2; Guido Ligabue2;
Cristina Mussini1; Paolo Raggi3; Jonathon Leipsic4; Don D. Sin5 and
Giovanni Guaraldi1
1
Infectious Disease Clinic, AOU Policlinico di Modena, Modena, Italy.
2
Radiology, AOU Policlinico di Modena, Modena, Italy. 3Mazankowski
Alberta Heart Institute, Edmonton, Canada. 4Radiology, University
of British Columbia, Vancouver, Canada. 5Medicine, University of
British Columbia, UBC James Hogg Research Center, Vancouver,
Canada.
Introduction: The aim was to determine the prevalence of lung and
heart abnormalities on thoracic CT scans in HIV-infected patients who
were treated with antiretroviral therapy (ART).
Material and Methods: Thoracic CT scans of 903 patients infected
with HIV (mean age 4897 yrs, 29% females) were reviewed by three
radiologists by consensus. Patients were phenotyped according to
smoking status, pack years and years since cessation for ex-smokers.
Individuals known to have active lung or heart disease at the time
of CT scanning were excluded. Multimorbidity lung and heart disease (MLHD) was defined by the presence of 2 lung or heart
abnormalities on the CT scan.
Results: Prevalence of lung abnormalities were: 326 patients (36.1%)
with emphysema, 271 (30.0%) with bronchiolitis, 44 (4.9%) with noncalcified lung nodules, 568 (63%) with significant bronchial wall
thickening, 150 (16.7%) with bronchiectasis, 9 (1%) with interstitial
lung disease. Overall, 445 patients (49.3%) had 2 lung abnormalities. Imaging findings suggestive of prior myocardial infarction (MI)
were found in 1.4% (13 patients); 26.6% (240 patients) had CAC
scores of 1 to 100, and 9.8% (89 patients) had CAC 100. 13.6% (123
patients) of the patients had CAC 100 and/or previous MI. MLHD
was present in 484 patients (53.6%) and among 78 patients (16%)
Prevalence of lung and heart CT abnormalities according to cumulative smoke exposure and according to
p-value
Emphysema
Stop
p-value
Never
Pack year
(p per
Never
smoking
(p per
smoker
group
trend)
smoker
group
trend)
B0.001
41 (19%)
35 (33%)
25 (27%)
24 (39%)
0.003 (0.01)
27 (13%)
18 (17%)
15 (16%)
14 (23%)
0.24 (0.29)
41 (19%)
010
1120
20
37 (23%)
62 (34%)
186 (54%)
B10 years 1020 years 20 years
( B0.001)
Bronchiolitis
27 (13%)
31 (19%)
57 (31%)
156 (45%)
B0.001
( B0.001)
Lung nodules
15 (7%)
8 (4.94)
5 (2.73)
16 (4.65)
0.26 (0.19)
15 (7%)
3 (2.9%)
5 (5.4%)
2 (3.28%)
0.39 (0.14)
Bronchial wall
104
83 (52%)
119 (65%)
262 (76%)
B0.001
104
65 (62%)
49 (53%)
40 (65%)
0.04 (0.05)
thickening
(49%)
( B0.001)
(49%)
Bronchiectasis
33 (16%)
21 (13%)
35 (19%)
61 (18%)
0.42 (0.29)
33 (16%)
18 (17%)
13 (14%)
17 (28%)
0.11 (0.97)
Interstitial lung
1 (0.5%)
0 (0%)
1 (0.6%)
7 (2%)
0.09 (0.03)
1 (0.5%)
0 (0%)
1 (1%)
0 (0%)
0.6
65 (30%)
55 (34%)
92 (50%)
233 (68%)
B0.001
65 (30%)
47 (45%)
34 (37%0)
32 (52%)
0.005(0.02)
0.11 (0.048)
9 (4%)
13 (12%)
5 (5%)
6 (9%)
0.039 (0.02)
0.004
16 (7.5%)
9 (8%)
13 (14%)
8 (13%)
0.25 (0.42)
24 (11.%)
18 (17%)
15 (16%)
12 (19%)
0.26 (0.1)
78 (36%)
55 (52%)
38 (41%)
33 (54%)
disease
Multimorbidity
lung
Myocardial
( B0.001)
9 (4%)
4 (2.5%)
9 (5%)
25 (7%)
16 (7.5%)
8 (5%)
17 (9%)
49 (14%)
infarction
CAC 100
(0.002)
Multimorbidity
24 (11%)
10 (6%)
23 (13%)
66 (19%)
heart
Multimorbidity
lung and heart
B0.001
( B0.001)
78 (36%)
59 (36%)
98 (53%)
249 (72%)
B0.001
( B0.001)
0.013
(0.017)
disease (MLHD)
141
Poster Abstracts
who never smoked. Table 1 describes CT findings according to pack
year and stop smoking groups vs never smokers.
MLHD increased proportional to cumulative smoking history
(p for trend B0.001) and decreased in proportion to the number of
years since smoking cessation (p for trend0.017). Independent
predictors for MLHD were: age (OR 1.07, CI 1.051.10), sex
(OR 1.59, CI 1.152.19), current smoking (OR 1.76, CI 1.08
2.89), and pack-years history of smoking (OR 1.03, CI 1.021.05).
In patients who never smoked, nadir CD4B200 was significantly
associated with MLHD after adjustment for age and sex (OR 1.98, CI
1.983.63).
Conclusions: MLHD is common in HIV-infected individuals even in
non-smokers. Reduced CD4 count (hence severity of HIV infection)
may be an important risk factor for chronic lung and heart disease.
Thoracic CT scans may provide an excellent screening tool to detect
MLHD in HIV-infected patients.
Conclusions: Close follow-up of HPV and SIL should be promoted
particularly in men and in untreated individuals. We cannot exclude
behavioural variables linked to risky sex and reinfection.
P185
Factors associated with HPV-DNA clearance in a cohort of
HIV-positive patients: role of cART and gender
Elisa Suardi1; Francesca Bai1; Laura Comi1; Alessandro Pandolfo1;
Marco Rovati2; Ambra Barco1; Serena Dalzero3; Barbara Cassani4;
Giulia Marchetti1 and Antonella D’Arminio Monforte1
1
Infectious Diseases, San Paolo Hospital/University of Milan, Milan,
Italy. 2General Surgery, San Paolo Hospital/University of Milan, Milan,
Italy. 3Gynaecology and Obstetrics, San Paolo Hospital/University
of Milan, Milan, Italy. 4Pathology, San Paolo Hospital/University of
Milan, Milan, Italy.
Introduction: We aimed to assess any factors associated with
dysplasia regression and with HPV clearance in a cohort of HIV
patients, with particular focus on cART and gender.
Methods: Asymptomatic HIV patients of the San Paolo Infectious
Disease (SPID) cohort who underwent anoscopy/gynaecological
evaluation were enrolled. Anal/cervical brushing were analyzed for:
HPV-PCR detection/genotyping (HR-HPV), cytologic abnormalities
(Bethesda System 2001: LSIL-HSIL). Demographics and HIV-related
parameters were evaluated at baseline. Activated CD8/CD38
lymphocytes were measured (flow citometry). Patients were examined at baseline (T0) and at 1218 months visit (T1). HPV clearance
was defined as negativisation of HPV at T1; SIL regression (SIL-R)
and progression (SIL-P) were defined as change from HSIL/LSIL to a
lower-grade/absence of dysplasia and as change from absence of
HSIL/LSIL to a higher-grade dysplasia at T1, respectively. Mann
Whitney test, Chi-square test and multivariate logistic regression
were used.
Results: A total of 189 patients were examined, 60 (32%) were
women. One hundred fifty patients (79%) were HPV, 113 (75%)
harboured HR-HPV; 103 (68%) showed LSIL/HSIL at T0 (32% of
women and 65% of men) (all were HPV-positive). No differences in
demographics and HIV-related markers were found between patients
with SIL-P (33, 41%) and patients with SIL-R (47, 59%). HPV
patients who cleared HPV (28, 18%) were found to be more
frequently female, heterosexual infected, more frequently on cART
and with lower Log10 HIV-RNA and lower levels of CD8/CD38 %
compared with HPV persistence group (Table 1).
No differences in PI exposure were found between the two groups
(p .08). Interestingly, also when only HR-HPV were considered,
clearance was associated with exposure to cART (naı̈ve 4%, vs cART
86%, p .048). In multivariate analysis, heterosexuals (AOR 5.123,
95% CI 1.517.5 vs homosexuals) were independently associated to
HPV clearance, whereas CD8/CD38% (AOR 0.44, 95% CI 0.65
1.01 for each % more) were predictive of HPV persistence.
Abstract P185Table 1. Characteristics of study population
according to HPV clearance
Patients that
Patients that
Characteristics of
cleared HPV
remain HPV
Study Population
(n 28)
(n 122)
Female Sex
11 (39%)
19 (15%)
0.05
Heterosexual
epidemiology
16 (57%)
29 (23%)
0.001
Log10 HIV-RNA*
p
1.77 (1.591.77)
1.77 (1.594.16)
0.038
cART
28 (100%)
122 (81%)
0.015
CD8/CD38%*
1 (12.7)
2 (16)
0.001
P186
Relationship between innate immunity, soluble markers
and metabolic-clinical parameters in HIV patients ART
treated with HIV-RNA B50 cp/mL
Chiara Dentone1,2; Daniela Fenoglio3; Alessio Signori4;
Giovanni Cenderello5; Alessia Parodi6; Federica Bozzano7;
Michele Guerra8; Pasqualina De Leo9; Valentina Bartolacci10;
Eugenio Mantia11; Giancarlo Orono12; Francesca Kalli6;
Francesco Marras13; Paolo Fraccaro14; Mauro Giacomini15;
Giovanni Cassola5; Bianca Bruzzone16; Giuseppe Ferrea1;
Claudio Viscoli17,18; Gilberto Filaci19,20; Andrea De Maria21,22 and
Antonio Di Biagio17,18
1
Infectious Diseases, Sanremo Hospital, Sanremo, Italy. 2Center of
Excellence for Biomedical Research, University of Genoa, Sanremo,
Italy. 3DIMI, Center of Excellence for Biomedical Research, University
of Genoa, Genoa, Italy. 4Section of Biostatistics, University of Genoa,
Genoa, Italy. 5Infectious Diseases, Galliera Hospital, Genoa, Italy.
6
Center of Excellence for Biomedical Research, University of Genoa,
Genoa, Italy. 7DIMES, Center of Excellence for Biomedical Research,
University of Genoa, Genoa, Italy. 8Infectious Diseases, La Spezia
Hospital, La Spezia, Italy. 9Infectious Diseases, Savona Hospital,
Savona, Italy. 10Infectious Diseases, Albenga Hospital, Albenga, Italy.
11
Infectious Diseases, Alessandria Hospital, Alessandria, Italy.
12
Infectious Diseases, Amedeo di Savoia Hospital, Torino, Italy.
13
Immunology, Giannina Gaslini Institute, Genoa, Italy. 14DIBRIS,
University of Genoa, Genoa, Italy. 15DIBRIS, Center of Excellence for
Biomedical Research, University of Genoa, Genoa, Italy. 16UO
Hygiene, San Martino Hospital IRCCS, Genoa, Italy. 17Infectious
Diseases, San Martino Hospital IRCCS, Genoa, Italy. 18University of
Genoa, Genoa, Italy. 19DIMI, University of Genoa, Genoa, Italy.
20
Center of Excellence for Biomedical Research, San Martino
Hospital, Genoa, Italy. 21Infectious Diseases, San Martino Hospital
IRCCS, Genoa, Italy. 22Center of Excellence for Biomedical Research,
University of Genoa, Genoa, Italy.
Introduction: The persistence of immune activation and inflammation in HIV patients with HIV-RNA (VL) undetectable causes many comorbidities [13]. The aim of this study is to correlate monocytes
(m) and NK cell activation levels, soluble markers and oxidative stress
with clinical, biochemical and metabolic data in HIV-1 infected
patients with VL 550 copies (cp)/mL on antiretroviral therapy.
Materials and Methods: Multicentre, cross-sectional study in
patients with VL 550 cp/mL and on antiretroviral therapy by at
142
least six months. We studied: activation/homing markers (CD38, HLADR, CCR-2, PDL-1) on inflammatory, intermediate, proinflammatory
m; activatory receptors NKp30, NKp46 and HLA-DR on NK cells;
soluble inflammatory (sCD14, adiponectina, MCP-1) and stress
oxidative markers (dRoms, antiRoms). Univariate analyses are
performed with non-parametric and Pearson tests. The significant
correlations were adjusted for possible known confounding factors
(smoking, Cytomegalovirus IgG serology, Raltegravir, Protease Inhibitor [PI] therapy and HCV-RNA) with multivariate analysis.
Results: In the 68 patients the positive correlation between age and
antiRoms was significant also after adjustment for PI use (p 0.05).
The% CD8T was associated with% proinflammatory m (p 0.043)
and with their expression of CCR2 mean fluorescence intensity (MFI)
(p 0.012). The% NKp46 was positively correlated with CD4T
count (p 0.001). The fibrinogen was positively associated with
dRoms (p 0.052) and the positive correlation between triglycerides
and antiRoms has been confirmed (p B0.001); the impact of
antiRoms on HDL/triglycerides ratio (p 0.006) was observed after
adjustment for PI use. The BMI was associated with smoking
(p 0.011). Only the maraviroc-treated patients showed minimal
arterial pressure, fibrinogen and antiRoms lower (p0.001, 0.004 e
0.006) and sCD14 values higher (p 0.029).
Conclusions: Patients with long history of HIV infection and stable
immunological and virological status showed interactions between
acquired and innate immunity activation; moreover, the levels of
some metabolic and inflammatory parameters correlate with oxidative stress values and innate immunity activation. The age, BMI
and smoking impact metabolic and immunological parameters. The
correlations between antiretroviral drugs and clinical-immunological
parameters need further confirmations.
References
1. Benjamin LA, Bryer A, Emsley HC, Khoo S, Solomon T, Connor MD.
HIV infection and stroke: current perspectives and future directions.
Lancet Neurol. 2012;11(10):87890.
2. Kaplan RC, Sinclair E, Landay AL, Lurain N, Sharrett AR, Gange SJ,
et al. T cell activation and senescence predict subclinical carotid
artery disease in HIV-infected women. J Infect Dis. 2011;203(4):
45263.
3. Deeks SG. HIV infection, inflammation, immunosenescence, and
aging. Ann Rev Med. 2011;62:14155.
P187
Cerebrospinal fluid biomarkers in patients with plasma HIV
RNA below 20 copies/mL
Poster Abstracts
Andrea Calcagno1; Cristiana Atzori2; Alessandra Romito3;
Sara Ecclesia1; Daniele Imperiale2; Sabrina Audagnotto1;
Maria Chiara Alberione1; Alice Trentalange1; Giovanni Di Perri1 and
Stefano Bonora1
1
Department of Medical Sciences, University of Torino, Torino, Italy.
2
Unit of Neurology, Ospedale Maria Vittoria, ASLTO2, Torino, Italy.
3
Laboratory of Immunology, Ospedale Amedeo di Savoia, ASLTO2,
Torino, Italy.
Introduction: Low level HIV-1 CSF replication (CsfLLV) is often found
even in patients with controlled plasma viraemia. The clinical
consequences of such finding are uncertain; however, both symptomatic neurological disturbances and neurocognitive disorders may
arise in the context of CSF-escape. Two reports suggested that low
level replication in the CSF may be associated with increased CSF
neopterine although the impact on other markers of neuroinflammation/damage is currently unknown.
Materials and Methods: Patients with neurocognitive disorders, new
neurological symptoms or followed in longitudinal studies were
included provided that they were on HAART, with last available viral
load below 20 copies/mL and without central nervous system (CNS)involving infections/neoplasms. After brain Magnetic Resonance
(MR) CSF HIV RNA (CAP/CTM HIV-1 v2.0) and biomarkers [total tau
(t-tau), phosphorylated tau (p-tau), 142 Beta amyloid (Beta42),
neopterine and S100beta] were measured through validated methods. Data are presented as medians (IQR); non-parametric tests are
used for all analysis.
Results: 70 patients [66.7% male, median age 47.8 years (4056),
median BMI 22.2 kg/m2 (2024)] were enrolled. Current and
nadir CD4 cell count were 379 (219656) and 116 cell/mm3
(46225); HIV RNA was undetectable since 19.7 months (953).
CSF HIV RNA was undetectable in 24 (34.3%), below 20 copies/mL
in 26 (37.1%), above 20 copies/mL in 25 patients [35.7%, median
69 copies/mL (41134]). Median (IQR) CSF biomarkers values were
as follows: t-tau 109 pg/mL ( B75161), p-tau 31.6 pg/mL (23.4
35.4), Beta42 818 pg/mL (623973), neopterine 0.58 ng/mL
(0.450.87) and S100beta 149 pg/mL (110186). Patients with
CsfLLV did not show significant differences as for demographic,
therapeutic, virological, radiological variables. t-tau (134 vs 92.6,
p0.05) and Beta42 (953 vs 675, p0.007) were higher in
patients with CsfLLV. Neopterine levels were directly associated
with p-tau (rho 0.42, p 0.01), with CSF HIV RNA (rho 0.24,
p0.06). and inversely with current CD4 cell count (rho 0.29,
p03).
Conclusions: In patients with controlled HIV viraemia (below 20
copies/mL), CSF total tau, Beta42 and neopterine were higher in
patients with detectable HIV RNA. Prospective and adequately
Patients’ characteristics
Age, years (median, IQR)
Sex, n males (%)
49 (4654)
46 (68)
Prior AIDS events, n (%)
25 (37)
Co-infection HCV and/or HBV, n (%)
21 (31)
Current smoking, n (%)
42 (62)
BMI (median, IQR)
Nadir TCD4 (median, IQR)
Time since HIV diagnosis, years (median, IQR)
Time on antiretroviral therapy, years (median, IQR)
CD4T at enrolment (median, IQR)
Antiretroviral therapy at enrolment, n (%)
23.5 (20.625.5)
202 (67316)
19 (1622)
15 (916)
488 (370607)
PI 37 (54), RAL 39 (39), MVC 43 (63), NNRTI 26 (38)
143
Poster Abstracts
powered studies are warranted for evaluating the clinical significance
of compartmental viral replication and immune activation.
P189
Beatriz Dı́az-Pollán1; Vicente Estrada2; Manuel Fuentes-Ferrer3;
Dulcenombre Gómez-Garré4 and Jesús San Román-Montero5
1
Medicina Interna, Hospital Universitario La Paz, Madrid, Spain.
2
Medicina Interna III, Hospital Clı́nico San Carlos, Madrid, Spain.
3
Preventive Medicine Department, Hospital Clı́nico San Carlos, ,
Madrid, Spain. 4Vascular Biology Research Laboratory, Instituto de
Investigación Sanitaria del Hospital Clı́nico San Carlos (IdISSC),
Madrid, Spain. 5Departamento de Medicina y Cirugı́a, Universidad
Rey Juan Carlos, Alcorcón, Spain.
P188
Depression in HIV-positive women is associated with
changes in antiretroviral treatment regimens
Claus Philippe Küpper-Tetzel1; Siri Göpel1; Pavel Khaykin1;
Timo Wolf1; Christoph Stephan1; Eva Herrmann2;
Hans-Reinhard Brodt1 and Annette Haberl1
1
Department of Infectious Diseases, Medical Clinic II, University Clinic
Frankfurt, Frankfurt, Germany. 2Department of Biostatistics and
Mathematic Modelling, University Clinic Frankfurt, Frankfurt,
Germany.
Introduction: Depression is a co-morbidity of clinical significance in
HIV-positive patients with an estimated prevalence of more than
20%. Sex and gender-related differences in depression are well
described in HIV-negative populations, demonstrating that more
women are being affected. So far little is known about frequency and
characteristics of depression in HIV-positive men and women.
Materials and Methods: Primary objective of our prospective
epidemiological study was the evaluation of the Beck score for
depression in male and female patients of the Frankfurt HIV Cohort.
The Beck Depression Inventory (BDI-II) is a self-report symptom
inventory made up of 21 questions, each with 4 possible answers,
correlating with a certain point value. Interpretation: score 1419:
mild depression; score 2028: moderate depression; score ]29:
severe depression. Secondary objectives of the analysis were factors
that might possibly influence the disposition for depression in HIVpositive patients, e.g. age, antiretroviral treatment history, comorbidities and socioeconomic status.
Results: Between January and October 2013, 348 patients were
enrolled in the study, 161 women and 187 men of the Frankfurt HIV
Cohort, who had a routine appointment at the HIV-Center of the
University Clinic Frankfurt. The mean age of all study participants
was 45 years (range 2280). The majority of patients were on
antiretroviral therapy (91%) at study entrance. The median BDI-II
score in all patients was 8 (049); in female patients 10 (042), in
male patients 6 (049), respectively (Table 1). Significant more
women than men showed a score for moderate depression
(p 0.006). Factors associated with a BDI-II score ]20 in women
were older age ( 45 years), living alone, unemployment and the
number of prior changes in antiretroviral therapy.
Conclusions: Depression in people living with HIV shows sex and
gender-related differences that might also influence antiretroviral
treatment strategies. HIV specialists should be aware of these
gender-specific aspects and consider routine screening for depression especially in female patients of older age or those with multiple
therapy changes in history.
and women
Distribution of BDI-II scores in men
All patients
Men
Women
n 348
n187
n 161
BDI-II score 119 n (%)
288 (82%)
165 (88%)
123 (76%)
BDI-II score 2028 n (%)
41 (12%)
13 (7%)
28 (18%)
BDI-II score ]29 n (%)
19 (6%)
9 (5%)
10 (6%)
Lp-PLA2 levels in HIV-infected patients
Introduction: HIV-infected patients show an increased risk of
cardiovascular disease (CVD). In the general population, lipoprotein-associated phospholipase A2 (Lp-PLA2) appears to be an
independent predictor of CVD. We aimed to study associations
between Lp-PLA2 plasma levels and other risk factors for CVD in HIV
patients.
Materials and Methods: A cross-sectional, comparative study of
two series of cases (HIV patients, n116 and age-matched nonHIV healthy controls, n 113) was conducted. Eighty-seven percent
HIV patients on antiretroviral therapy (ART), 72.4% with HIV-1 viral
load B50 cop/mL. Inflammatory biomarkers (CRP, Lp-PLA2) and
internal carotid intima-media thickness (IMT) were measured and
CVD risk (Framingham and SCORE algorithms) was calculated. Univariate and multivariable associations between these variables were
performed.
Results: HIV patients presented higher Lp-PLA2 levels [276.81 ng/mL
(209.71356.58)] than uninfected healthy controls [220.80 ng/mL
(172.70256.90)], p50.01. In univariate analysis of the global
sample, only cigarette smoking was associated with higher Lp-PLA2
levels, p50.001. In HIV group, female and smoker patients showed
higher Lp-PLA2 levels, p50.05. No significant association was found
between Lp-PLA2 levels and another CVD risk factors, carotid IMT,
Framingham and SCORE algorithms, ART, HIV-1 viral load neither
and CD4 T lymphocyte count. In multivariate analysis, cigarette smoking remained significantly associated with Lp-PLA2 levels [b64.8
(95% CI 10.8118.9) ng/mL, p0.020].
Conclusions: HIV-infected patients present higher Lp-PLA2 levels
than healthy controls, and in this population, tobacco smoking is
significantly associated with increased Lp-PLA2 levels. Smoking
cessation should be a priority in CVD prevention in HIV-infected
patients.
P190
Liver fibrosis is associated with cognitive impairment in HIVpositive patients
Nicoletta Ciccarelli1; Massimiliano Fabbiani1; Pierfrancesco Grima2;
Silio Limiti1; Iuri Fanti1; Annalisa Mondi1; Roberta Gagliardini1;
Alessandro D’Avino1; Alberto Borghetti1; Roberto Cauda1 and
Simona Di Giambenedetto1
1
Institute of Clinical Infectious Diseases, Catholic University of Rome,
Rome, Italy. 2Institute of Infectious Diseases, S. Caterina Novella
Hospital, Galatina, Italy.
Introduction: The aim of our study was to investigate the potential
relationship between liver fibrosis (LF) and cognitive performance in
HIV patients.
Materials and Methods: We performed a cross-sectional cohort study
by consecutively enrolling HIV patients during routine outpatient
visits at two clinical centres in Italy. Subjects with decompensated liver
disease were excluded. All subjects underwent a comprehensive
neuropsychological battery exploring memory, attention, psychomotor
144
speed and language; cognitive impairment was defined as at least two
abnormal [1.5 SD below the mean for appropriate norms] cognitive
domains. LF was explored by calculating FIB4 index; in a subgroup of
patients, LF was also assessed by transient elastography. Factors
associated with cognitive impairment were investigated by logistic
regression models.
Results: A total of 413 patients [77% males, median age 46 (IQR 39
52), 17% with past AIDS-defining events, 19% past IDU, 3% with
diabetes, 94% on cART, 90% with HIV RNA B50 copies/mL, 18% coinfected with HCV] were enrolled. Seventeen patients (4%) had FIB4
3.25 and 14/129 (3%) had liver stiffness 14KPa. Forty-seven
patients (11%) were diagnosed with cognitive impairment. At multivariate analyses patients with FIB4 1.45 showed a higher risk of
cognitive impairment in comparison with those with lower values (OR
2.19, 95% CI 1.024.72; p0.044) after adjusting for education (OR
0.79, 95% CI 0.710.88; p B0.001), past IDU (OR 1.69, 95% CI 0.67
4.23; p0.264), diabetes (OR 2.35, 95% CI 0.628.86; p0.207), HIV
RNA B50 copies/mL (OR 0.47, 95% CI 0.191.14; p 0.095) and HCV
co-infection (OR 0.88, 95% CI 0.332.39; p0.807). Analyzing any
single cognitive domain, a higher risk of abnormal psychomotor speed
was associated with fibroscan score 14KPa in comparison with
fibroscan score B7KPa (OR 285.07; 95% CI 2.4233574.06; p
0.020) after adjusting for education (OR 0.54, 95% CI 0.310.92;
p0.024), age (for 10 years increase) (OR 2.03, 95% CI 0.557.53;
p0.288), past IDU (OR 4.43, 95% CI 0.357.57; p0.526), HIV RNA
B50 copies/mL (OR 0.01, 95% CI 0.000.18; p0.003), HIV history
(for 1 year increase) (OR 0.96, 95% CI 0.831.12; p 0.641), CD4 cells
count at nadir (OR 1.10, 95% CI 0.562.16; p0.779), and HCV coinfection (OR 0.06; 95% CI 0.001.93; p 0.113).
Conclusions: In HIV-infected patients higher LF, estimated through
non-invasive methods, is associated to a higher risk of cognitive
impairment.
P191
The CD4:CD8 ratio is associated with IMT progression in
HIV-infected patients on antiretroviral treatment
Enrique Bernal1; Jose Serrano1; Ana Perez1; Salvador Valero1;
Eva Garcia1; Irene Marı́n2; Angeles Muñoz1; Jose Miguel Gomez
Verdú1; Carmen Vera1 and Alfredo Cano1
1
Reina Sofia Hospital, Infectious Disease Unit, Murcia, Spain. 2Reina
Sofia Hospital, Cardiology, Murcia, Spain.
Introduction: Inversion of the CD4:CD8 ratio ( B1) has been identified as a hallmark of immunosenescence and an independent
predictor of mortality in the general population. We aimed to assess
the association between the CD4:CD8 ratio and intima-media
thickness (IMT) progression in treated HIV-infected patients as a
marker of early atherosclerosis.
Materials and Methods: A longitudinal study during three years was
conducted in 120 HIV-infected patients receiving antiretroviral
treatment (ART). We analyzed the associations between the CD4:CD8
ratio, cardiovascular risk factor and antiretroviral (ARV) treatment
and progression of subclinical atherosclerosis assessed using carotid
IMT at baseline and after three years.
Results: Finally, 96 patients completed the study. Seventy-six (79.1%)
patients were male, aged 44910 years, 39 (40.6%) were on
treatment with Protease inhibitors, 49 (51.04%) with non-nucleoside
reverse transcriptase inhibitors (NNRTI), 6 (6.25%) with integrase
inhibitors, 3 (3.12%) with maraviroc and 2 (2.08%) only with
nucleoside reverse transcriptase inhibitors (NRTI). The mean of
ARV exposition was 6.995.9 years. Twenty six (27 %) patients had
family history of ischemic heart disease, 51 (53.12%) were smokers,
12 (12.5%) hypertensive, 4 (4.16%) type 2 diabetes, 23 (23.9%) with
Poster Abstracts
dyslipidemia and 31 (32.3%) were infected with C hepatitis virus.
Baseline IMT was significantly associated with age (rho 0.497;
pB0.001), basal glucemia (rho0.323; p0.001), triglycerides (rho
0.232; p0.023), Framingham score (rho 0.324; p0.001), CD4:
CD8 ratio (rho 0.176; p0.05) and dyslipidemia (0.7290.16
mm vs 0.6390.11 mm; p 0.029). In multivariable analysis where
cardiovascular risk factor and ARV were included, IMT progression
was inversely associated with CD4:CD8 ratio (OR 0.283; CI 95%
0.0990.809; p 0.019) and treatment with NNRTI (OR 0.283; CI
95% 0.0990.809; p 0.019).
Conclusions: The inversion of CD4:CD8 ratio in treated HIV-infected
patients is independently associated with IMT progression, a marker
of age-associated disease. Therefore, it might be clinically useful as
predictor of cardiovascular events. Surprisingly, there was a positive
correlation between receiving NNRTI and progression of IMT.
P192
HIV-1 tat and rev upregulates osteoclast bone resorption
Nicholas Chew1; Eemin Tan2; Lei Li1 and Ryan Lim2
1
Infectious Diseases, National University of Singapore, Singapore.
2
Obstetrics and Gynaecology, National University of Singapore,
Singapore.
Introduction: Disruption in bone homeostasis with increased
osteoclastic resorption may lead to osteoporosis. HIV tat has been
found to increase differentiation of precursor cells into osteoclast
(OC) [1]. Presence of soluble HIV proteins in virally suppressed HIV
patients on ART may drive a bone resorption phenotype. We
investigated the role of soluble HIV proteins (tat, gp120 Mn and
Bal, rev and p55-gag) on osteoclastogenesis and OC resorptive
capacity.
Methods: Mouse monocyte RAW 264.7 cells were cultured in vitro
and induced to differentiate into OCs with 50 ng/mL RANKL and
25 ng/mL mCSF. Medium was supplemented with 100 ng/mL of
recombinant HIV tat, gp120 (Mn and Bal), rev, nef and p55-gag,
respectively, with zolendronate as negative control. Differentiated
OCs were stained for TRAP and counted. OC resorption function was
examined by culturing differentiated OCs (in the presence of
respective HIV proteins) on dentin-coated plates and examining the
following (i) sealing zone formation, (ii) volume of resorption pits and
(iii) area of resorption pits per field using confocal microscopy.
Expression of OC specific genes including NFATc1 and cathepsin K was
investigated by qPCR. Reactive oxygen species (ROS) production is
essential in RANKL-induced OC differentiation [2,3]; effect of these
proteins on ROS production was assessed using the fluorescent
H2DCFH-DA. Mean fluorescence intensity was then measured by
flow cytometry. TNFa production by OC precursors when incubated
with tat and rev was measured by ELISA.
Results: Tat and rev treatment was associated with increased OC
formation by 70 and 26%, respectively (p B0.01), relative to control,
while zolendronate significantly inhibited OC formation by 75%.
Gp120 Mn and Bal, nef and p55-gag treatment had no effect on OC
differentiation. Interestingly, neither tat nor rev treatment caused
significant increases in sealing zone formation but increased dentin
resorption pit area by 28 and 19%, respectively, and resorption pit
volume by 11 and 6%, respectively. Tat protein treatment was
associated with upregulation of NFATc1 and cathepsin K mRNA
expression by 20 and 15%, respectively. Incubation with tat and rev
led to a dose-dependent increase in intracellular ROS production in
the monocytes and OC precursors and significant upregulation in
TNFa cytokine production by the OC precursors.
Conclusions: In addition to their effect of OC differentiation, we
demonstrated the effects of tat and rev on OC resorption. HIV tat
145
and rev are both biologically active in driving a pro-osteoclastic
phenotype.
References
1. Gibellini D, De Crignis E, Ponti C, Borderi M, Clò A, Miserocchi A,
et al. HIV-1 Tat protein enhances RANKL/M-CSF-mediated osteoclast
differentiation. Biochem Biophys Res Commun. 2010;401(3):42934.
2. Kim MS, Yang YM, Son A, et al. RANKL-mediated reactive oxygen
species pathway that induces long lasting Ca2 oscillations essential
for osteoclastogenesis. J Biol Chem. 2010;285(10):691321.
3. Lee NK, Choi YG, Baik JY, et al. A crucial role for reactive oxygen
species in RANKL-induced osteoclast differentiation. Blood. 2005;
106(3):8529.
P193
Tackling cardiovascular co-morbidities in HIV-positive
patients: who, how and where?
Sophie Rolls; Emma Denneny; Rebecca Marcus and
Rebecca O’Connell
Newham University Hospital, Barts Health NHS Trust, HIV Medicine,
London, UK.
Introduction: Cardiovascular disease (CVD) is a significant cause of
non-AIDS-related morbidity and mortality in HIV-positive individuals
[1]. Management of CVD and associated risk factors in HIV are
complicated by drug interactions [2]. Optimal management can
require specialist input. A previous cohort review highlighted CVD,
comorbidity and cardiovascular (CV) risk in our patients [3]. In
response, a combined HIV and cardiovascular monthly clinic was
established: an HIV consultant works in real time with a cardiologist.
The clinic manages CV disease, complex CV co-morbidities e.g.
refractory hypertension, hyperlipidaemia, and assesses primary
prevention. A dietician works alongside the clinic.
Aims: Describe the clinic caseload; record clinic interventions and
outcomes; recommend service development.
Materials and Methods: We conducted a retrospective notes review
of patients attending the co-morbidity clinic from January 2012 to
May 2014. Data collected: demographic, HIV, CVD, CV risk, investigations and clinical interventions.
Results: From a cohort of approximately 960 patients (70% African),
60 (6%) were seen in the co-morbidity clinic over the specified time
period. Median age was 53 (range 24-80). Although 60% of our
cohort is female, 43% (26/60) of the CVD clinic were female. 42
(70%) were African. The mean CD4 was 560 (range 48-1339). All
patients were on ART and 6 (10%) had a detectable viral load 400
copies/mL. Clinic caseload: i) CVD: 9 had a prior CV event (ACS or
CVA); 5 had CCF; new diagnoses included LVH (2), cardiac dysfunction
(6); AF (2); atrial thrombus (1). ii) Co-morbidities: 48(80%) had
hypertension 10 (16.6%) were on quadruple therapy; 17 (28%) had
diabetes; 35 (58%) were on a statin. Three had their smoking status
clearly documented. Seventeen (28%) were referred to the dietician.
Investigations included echo, 24-hour BP/ tape, CT angio, cardiac MR.
Conclusions: The joint clinic facilitated real-time decision making on
clinical interventions. Patient access to cardiac investigations was
expedited. Patients attended fewer outpatient appointments. Both
cardiology and HIV clinicians preferred the benefits of joint working.
Clinical outcomes were difficult to assess and will need further
definition. Recommendations for development include: improved CV
risk assessment, improved outcome measures, links to smoking
cessation services.
Poster Abstracts
2. Gedela K, Vibhuti M, Pozniak A, Ward B, Boffito M. Pharmacological management of cardiovascular conditions and diabetes in older
adults with HIV infection. HIV Med. 2014;15(5):25768.
3. Hartley A, Peterzan M, O’Connell R. Comorbidities, cardiovascular
risk factors and HIV: disease burden in an urban cohort over 40 years
old. HIV Med. 2012;13(Suppl 1):1385.
P194
Improvement of endothelial function after switching
previously treated HIV-infected patients to an NRTI-sparing
bitherapy with maraviroc
Enrique Bernal1; Jose Miguel Gomez Verdú1; Francisco Vera2;
Onofre Martinez2; Joaquin Bravo3; Carlos Galera4; Angeles Muñoz1;
Eva Garcia1; Jose Serrano1; Ana Perez1; Carmen Vera1; Irene Marı́n5
and Alfredo Cano1
1
Infectious Disease Unit, Reina Sofia Hospital, Murcia, Spain.
2
Infectious Disease Unit, Santa Lucia, Cartagena, Spain. 3Infectious
Disease Unit, Morales Meseguer, Murcia, Spain. 4Infectious Disease
Unit, Virgen de la Arrixaca, Murcia, Spain. 5Cardiology, Reina Sofia
Hospital, Murcia, Spain.
References
Introduction: Nucleoside reverse transcriptase inhibitor (NRTI) is
associated with endothelial dysfunction and proinflammatory effects. Maraviroc (MVC) is an antagonist of CCR5 receptor. CCR5 is the
receptor of RANTES (Regulated on Activation, Normal T Cell
Expressed and Secreted), a mediator of chronic inflammation and
endothelial function. Our aim was to evaluate the maintenance of
viral suppression and improvement of endothelial function in
virologically suppressed HIV-infected patients switched to an NRTIsparing combined antiretroviral therapy (cART) with MVC.
Material and Methods: This observational, non-interventional, multicenter study was performed at the Infectious Diseases Service of Santa
Lucia, Morales Meseguer, Virgen de la Arrixaca and Reina Sofı́a University
Hospital (Murcia, Spain). The selection criteria were to be asymptomatic
on a regimen with undetectable viral load (B50 HIV-RNA copies/mL) for at
least six months, no previous treatment with R5 antagonists, no evidence
of previous protease inhibitor (PI) failure and available R5 tropism test.
Twenty-one HIV-infected patients were selected after the treatment
regimen was changed to Maraviroc 150 mg/once daily plus ritonavirboosted PI therapy. Endothelial function was prospectively evaluated
through flow-mediated dilatation (FMD) of the brachial artery at baseline
and at weeks 24.
Results: We included 21 patients on treatment with PI in combination with 2 NRTI. The mean cART exposition was 133968.9 months.
Fourteen (66.6%) were males, aged 4999 years, 15 (71.4%) smokers,
4 (19.04%) family history of coronary heart disease, 1 (5.76%) type 2
diabetes and 3 (14.28%) hypertensive, mean total cholesterol was
185.5935 mg/dL, c-LDL 100.2937 mg/dL, tryglicerides 170.429
92.03 mg/dL, cHDL 52.6915.5 mg/dL, CD4 779,59383.28 cells/mL,
nadir CD4 187,96996 cells/mL. After 24 weeks of follow-up of a
switch to an NRTI-sparing regimen, 95.2% of HIV-patients on viral
suppressive cART maintained viral suppression and CD4 T cell
count. This cART switch improve endothelial function in patients with
lower baseline FMD levels after 24 weeks (baseline FMD 1.199
4.84 % to 24 weeks FMD 11.3297.27%; p0.002).
Conclusions: The results of our study show that a switch to an NRTIsparing bi-therapy with MVC improves endothelial function and
maintained the immune-virologic efficacy. This regimen emphasizes
the needs for further clinical studies to associate these achievements
with the incidence of non-AIDS-defining illnesses.
1. Hemkens LG, Bucher HC. HIV infection and cardiovascular disease.
Eur Heart J. 2014;35(21):137381.
146
P195
Mediterranean diet: the impact on cardiovascular risk and
metabolic syndrome in HIV patients, in Lisbon, Portugal
Sara Policarpo1; Emilia Valadas2; Teresa Rodrigues3 and
Ana Catarina Moreira4
1
Nutrition and Dietetics Department, University Hospital of Santa
Maria, Lisbon, Portugal. 2Infectious Diseases Department, University
Hospital of Santa Maria, Lisbon, Portugal. 3Laboratory of
Biomathematics, Faculty of Medicine of the University of Lisbon,
Lisbon, Portugal. 4Dietetics Department, Lisbon School of Health
Technology, Lisbon, Portugal.
Background: Metabolic syndrome (MS) is common in HIV-infected
individuals and it is associated with higher cardiovascular risk (CVR).
Mediterranean diet has been associated with a better metabolic
control and lower CVR.
Materials and Methods: From December 2013 to May 2014,
individuals between 18 and 65 years of age, who attended the
outpatient HIV Clinic at the University Hospital Santa Maria, Lisbon,
were selected. Adherence to Mediterranean diet was evaluated with
MedDietScore, a scale from 0 to 55 that punctuates 11 food items
according to the frequency of intake. Higher scores represent higher
adherence. CVR was assessed using D.A.D tool (classified as low,
moderate or high risk). We excluded individuals with opportunistic
disease, hospitalized in the past three months or with renal disease
diagnosis. All participants gave written informed consent.
Results: In the 571 HIV patients included, 67.1% (n383) were male,
91.6% (n523) Caucasian, with a mean age of 46.598.9 years. Patients
were divided in two groups: naı̈ve (7.5%; n43) or on antiretroviral
treatment (ART) (92.5%; n528). Mean length of HIV diagnosis was
6.796.5 years (naı̈ve) and 13.396.1 years (ART); TCD4 counts were
above 500 cel/mm3 in 55.8% (n24) and 67.6% (n357) of the
patients, respectively. MS was present in 33.9% (n179) of patients
in ART group and 16.3% (n7) in naı̈ve group. Presence of MS
was associated with ART group (OR2.7; p0.018). MS was also
associated with older age in this group (p0.000). Overall, mean
MedDietScore was 27.395.5. Higher score was associated with older
age (r0.319; p0.000). Naı̈ve patients presented a trend to higher
adherence to Mediterranean diet (65.1% vs 51.7% in naı̈ve group;
p0.090). No relation between MS and Mediterranean diet was found.
Higher CVR was associated with the presence of MS in the ART group
(p0.001). In this group, individuals with moderate CVR presented
higher rates of adherence to Mediterranean diet (p0.036) when
compared to low and high CVR score.
Conclusions: In this cross-sectional study, naı̈ve individuals presented
a trend to higher adherence to Mediterranean diet. On the ART
group, higher adherence to Mediterranean diet was found in
individuals with moderate CVR score. We think that this might
suggest that this group of patients adopt this diet only in the
presence of metabolic alterations or perceived CVR. Prospective
studies in HIV patients are required to determine the impact of
adherence to Mediterranean diet on the reduction of CVR.
Poster Abstracts
long-surviving patients with non-AIDS-related diseases. Government
hasn’t laid enough stress on it.
Materials and Methods: The interviews and questionnaire surveys
are conducted and analyzed to get information. The interviewees
include 81 AIDS long-surviving patients in three villages and several
hospitals in Shangcai, Zhumadian, and 18 AIDS-related decision
makers and health service providers.
Results: There are 79 long-surviving patients out of 81. 58 patients
have non-AIDS-related diseases. 21 patients get hypertension and 28
get HCV. 100% patients have been to the clinics with their real-name
IC cards for minor illness. 43 patients have been transferred to
assigned hospitals at the county level. Seven have the experience
utilizing health services in the municipal or provincial assigned
hospitals. The problem is on accessibility. 40 patients hope to get
more convenient and cheap health services. Among them, 37 say the
kinds and the amount of medicine in village clinics are not adequate.
Seven give up because of the expensive treatment expense. For 21
patients with hypertension, 3 buy medicine at the county-level
hospitals. The other 18 choose to buy at private pharmacy. For 28
patients with HCV, 3 are not aware they actually got HCV. Free
hepatic protector medicine is provided at village clinics. Up to 11
patients have not taken any treatment for HCV.
Conclusions: Patients with hypertension go to the private pharmacy
for medicine instead of higher level hospital because of lack of
medicine in clinics, far distance from hospitals, cumbersome
procedures in hospitals, limited dosage of prescriptions and too
little discount. The situation for patients with HCV is even worse.
It is predicted 70% of AIDS long-surviving patients have HCV. The
treatment is expensive and out of pocket. And free liver-protection
medicine does not work sometimes. Some patients working outside
their home town do not want to reveal their health situation to get
free medicine. The elderly with multiple co-morbidities need more
caring. Government should expand the scale of free medicine.
Hospitals need to improve medicine plans and assist on medicine
purchase. For patients, attitude decides everything.
P197
Smoking prevalence, readiness to quit and smoking
cessation in HIV patients in Germany and Austria
Olaf Degen1; Peter Arbter2; Peter Hartmann3; Christoph Mayr4;
Thomas Buhk5; Horst Schalk6; Helmut Brath7 and
Thomas Ernst Dorner8
1
Universitätsklinikum Hamburg-Eppendorf, Ambulanzzentrum,
Hamburg, Germany. 2Praxis Arbter, Krefeld, Germany. 3Praxisplus,
Münster, Germany. 4Ärzteforum Seestrasse, Berlin, Germany.
5
Infektionsmedizinisches Centrum Hamburg, Hamburg, Germany.
6
Schalk:Pichler Gruppenpraxis, Wien, Austria. 7Diabetesambulanz,
Gesundheitszentrum Süd, Wiener Gebietskrankenkasse, Wien,
Austria. 8Centre for Public Health, Medical University Vienna, Wien,
Austria.
P196
Research on demands and accessibility of health services
for AIDS long-surviving patients with AIDS-nonrelated
diseases: a survey in central China
Na He and Yingfeng Ye
School of Public Health, Fudan University, Shanghai, China.
Introduction: Compared with western countries, China started to
provide free medicine for AIDS patients years later, which leads to
the late emergence of problems on health service demands of AIDS
Introduction: Due to the interaction between smoking and the virus
and the antiretroviral therapy, the excess health hazard due to
smoking is higher in HIV patients than in the general population.
International studies suggest a higher prevalence of smoking in
HIV subjects compared to the general population. It was the aim of
the study to assess prevalence of smoking, to analyze determinants
of smoking, and to evaluate readiness to quit in HIV patients in
Germany and Austria.
Material and Methods: Consecutive patients with positive tested
HIV status, smokers and non-smokers, who are treated in seven
different HIV care centres in Austria and Germany were included.
Nicotine dependence was assessed with the Fagerström Test for
147
Nicotine Dependency (FTND), and stages of change by a standardized
readiness to quit questionnaire. Self-reported smoking status was
objectified by measuring exhaled carbon monoxide levels. Smokers
who wanted to quit were offered a structured smoking cessation
programme, and those who did not want to quit received a 1-minute
consultation. After six months, the smoking status of all included
subjects was reassessed.
Results: A total of 447 patients were included; the response rate was
92%. Prevalence of smoking was 49.4%. According to a multivariate
logistic regression analysis, lower age, male sex, lower educational
level, and smoking of the partner were significantly associated with
the smoking status. According to the FTND, 25.3% showed a low (0
2 points), 27.6 a moderate (34 points) and 47.1% a high (510 points)
dependency. Regarding stages of change, 15.4% of the smokers were
in the stadium precontemplation, 48.4 in contemplation, 15.4 in preparation and 10.0 in the stadium action. 11.0% were not assignable
in any stadium. Higher education level and lower grade of dependency were significantly associated with the wish to quit smoking.
Six months after the baseline examination, smoking cessation visits
(at least one session) was performed in 28.5% of the smokers. 13%
of the smokers have quit smoking, 23% have reduced smoking and
63% did not change smoking habits positively 6 months after the first
visit.
Conclusions: Prevalence rates for smoking in HIV subjects are
higher than in the general population. Readiness to quit is, however,
high, and 13% of smokers who have quit smoking after six months is
a remarkable short-term success. This observation underlines the
importance and feasibility of addressing smoking habits in HIV care.
PRE- AND POST- EXPOSURE PROPHYLAXIS
AND TREATMENT AS PREVENTION
P198
Two years of Truvada for pre-exposure prophylaxis
utilization in the US
Charlene Flash1; Raphael Landovitz2; Robertino Mera Giler3;
Leslie Ng3; David Magnuson3; Staci Bush Wooley4 and
Keith Rawlings4
1
Section of Infectious Diseases, Department of Medicine, Baylor
College of Medicine, Houston, TX, USA. 2Division of Infectious
Diseases, Department of Medicine, David Geffen School of Medicine,
Los Angeles, CA, USA. 3Drug Safety & Public Health, Gilead Sciences,
Foster City, CA, USA. 4Medical Affairs, Gilead Sciences, Foster City,
CA, USA.
Introduction: Truvada† (TVD) was approved in July 2012 by the US
FDA for pre-exposure prophylaxis (PrEP) in combination with safer
sex practices to reduce the risk of sexually acquired HIV-1 in high-risk
adults. This study explores the characteristics of US PrEP users and
their prescribers over the past two years.
Materials and Methods: A previously described algorithm was used
to identify TVD for PrEP by excluding use for HIV treatment, postexposure prophylaxis, and off-label treatment of chronic hepatitis B.
National electronic patient level data from 55% of all US retail pharmacies that dispensed TVD between January 1, 2012 and March 31,
2014 was collected. De-identified patient-level data including prescription refill data, medical claims and patient demographics were
analyzed via logistic regression to estimate the odds of change by
year.
Results: A total of 3253 unique individuals who started TVD for PrEP
between January 1, 2012 and March 31, 2014 were included in this
Poster Abstracts
New TVD for
Overall
Q1Q2
Q3Q4
Q1Q3
Q4 2013
2012
2012
2013
Q1 2014
3253
603
713
1057
880
Mean age in
years
38.1
38.4
38.7
37.8
37.7
% Younger
11.5
13.9
9.8
11.9
10.8
PrEP starts
Unique PrEP
users
B25 y/o
% Female
41.9
53.9
47.3
44.5
26.7
% Females
17.2
17.5
14.2
18.1
19.1
B 25 y/o
analysis. Women comprised 42.0% of PrEP users. Although mean age
was 38.111.9 years, with males being significantly older (39.3
11.6) than females (36.412.3), 11.5% of individuals were under 25
years old. The proportion of males under 25 was 7.4% (95% CI 6.3
8.7); significantly lower than that of women, 17.2% (95% CI 15.3
19.3). New starts have increased from 293 in 2012 to 472 Q1 2014.
During the 12-month period ending March 31, 2013 and March 31,
2014 the number of new starts among females dropped from 44.5%
to 22.9%.
Sixty-eight percent of TVD for PrEP prescriptions were written by five
specialties: internal medicine (19%), family practice (18%), infectious
diseases (11%), nurse practitioners (10%) and physician assistants
(10%).
Conclusions: The population of TVD for PrEP users in the US
nationally appears to be shifting demographically. It continues to
be initiated mostly by primary care providers. Over a two-year period
new starts of Truvada for PrEP have increased considerably among
males. While the overall proportion of female users decreased
between Q1 2012 and Q1 2014, females that started on PrEP are
younger than males. More community-level data on PrEP usage
will be helpful in informing local efforts to integrate PrEP in HIV
prevention messaging and services.
P199
Failure of daily tenofovir to prevent HIV transmission or the
establishment of a significant viral reservoir despite
continued antiretroviral therapy
Olubanke Davies1; Hannah Alexander2; Nicola Robinson3;
Matthew Pace4; Michael Brady2; John Frater4 and Julie Fox1
1
HIV, Guys and St Thomas’ NHS Trust, London, UK. 2Sexual Health
and HIV, Kings College Hospital, London, UK. 3Nuffield Department of
Medicine, University of Oxford, London, UK. 4Nuffield Department of
Medicine, University of Oxford, Oxford, UK.
Introduction: Truvada is licenced for HIV-1 prevention in the USA and
is available in the private sector. Tenofovir performed as well as
Truvada in the PARTNERS PrEP study and is used as HIV pre-exposure
prophylaxis (PreP) in some settings. The clinical efficacy of Tenofovir
for PrEP outside a clinical trial is unknown. Antiretroviral therapy
(ART) at acute HIV-1 infection (AHI) limits the size of the reservoir,
optimizing the chance of maintaining viral control off therapy. As
such ART at acute HIV infection is proposed to offer a functional cure
in a minority of subjects. We present two cases where Tenofovir PrEP
failed to prevent HIV acquisition and failed to limit viral reservoir.
148
infection
Poster Abstracts
Summary of the two cases of HIV acquisition whilst receiving tenofovir monotherapy for hepatitis B
Patient A
Patient B
HIV Positive (HIV negative)
14/02/2014 (negative 02/12/2013) 02/06/2014 P24 Ag positive Antibody negative
hepatitis B positive
2008
1997
Hepatitis B treatments
2008 interferon intolerance: 2008
1997 interferon: 2000 3TC; 2002 Famciclovir;
-now Tenofovir
20022002 Adefovir monotherapy; 2011 - now Tenofovir
HIV seroconversion symptoms
mild fever 10/12/2013
severe pharyngitis, fever, rash
Baseline HIV viral load copies/ml
Hepatitis B viral load at HIV diagnosis
B50
undetectable
158 899
undetectable
HIV genotype
not possible
wild type
Tenofovir trough level Ng/ml at HIV diagnosis 48 (50th centile is 41)
awaited
Started ART
18/02/2014
06/06/2014
ART regimen
Eviplera
Truvada, Raltegravir, Darunavir, Ritonavir
HIV total DNA copies/million CD4 cells
1381
2746
Materials and Methods: Two individuals receiving tenofovir monotherapy for Hepatitis B monoinfection were diagnosed with AHI as
defined by a negative HIV antibody test within three months of a
positive HIV test following unsafe sex with casual male partners. Indepth histories were taken. Viral genotypes and Tenofovir drug levels
were measured from samples taken as close to HIV seroconversion as
possible and subsequent samples were analyzed for proviral Total
HIV-1 DNA by qPCR.
Results: Patient A had received tenofovir for the preceding six years
and always maintained an undetectable Hepatitis B viral load with no
concerns about adherence. Two weeks preceding the positive HIV
antibody test, he experienced mild symptoms (fever, pharyngitis) of
HIV seroconversion. HIV status was confirmed by a repeat fourth
generation HIV antibody test and by Western Blot and an HIV viral
load was undetectable. Tenofovir trough level at HIV diagnosis was
within normal limits. The regimen was intensified to Eviplera and a
total HIV-1 DNA was 1381 copies/million CD4 T cells. Patient B
received four regimens for hepatitis B treatment before starting
tenofovir monotherapy in 2011 and subsequently maintained an
undetectable hepatitis B viral load. After three years of tenofovir
monotherapy he developed a severe symptomatic seroconversion
illness and tested HIV antibody positive. The baseline HIV viral load
was 103,306 copies/mL. The regimen was intensified and total HIV-1
DNA was 2746 copies/million CD4 T cells.
Conclusions: Further investigation into the efficacy of tenofovir for
PrEP outside a clinical trial is required. ART at AHI does not always
lead to a low viral reservoir. To explore the possibility of replication
incompetent virus, viral outgrowth assays are underway.
P200
Attitudes and beliefs towards early ART initiation in MSM
with primary HIV infection
Victoria Parsons1; Kholoud Porter2; Richard Gilson1 and
Graham Hart1
1
London, London, UK. 2MRC CTU, University College London, London,
UK.
Introduction: ART initiation in primary HIV infection (PHI) could
reduce risk of transmission to sexual partners at a time of high
viraemia, although health benefit for the individual remains
unknown. We examined attitudes to early ART and associated beliefs
in men who have sex with men (MSM) with PHI.
Materials and Methods: Semi-structured face-to-face in-depth
interviews were conducted with 13 MSM aged ]16 years attending
a central London HIV clinic, within 12 months of date of estimated
HIV seroconversion. Audio recordings of interviews were transcribed
verbatim and analyzed thematically.
Results: Median age was 33 years (range 2247), majority were white
British (n 8), educated to university level (n11) and were not on
ART (n10). Great diversity in ART knowledge and expectations
around starting were observed, with some men assuming they
would be prescribed ART immediately upon diagnosis. Deferral until
CD4B350 came as a surprise and counterintuitive when put into
the context of treating other diseases. For many, the decision to start
ART was a balance of current and future health and quality of
life. Fear of side effects was prevalent, with many believing them
inevitable and a reason to avoid early ART. A perceived lack of
‘‘good quality’’ evidence showing a health benefit of early ART
caused confusion. Avoiding the decision to start or deferring to their
HIV clinician was common, however reported clinicians’ views also
varied. Some men voiced a desire to be proactive and start early ART
to control viral replication. In these cases men also reported a belief
that ART could be temporary as they expected a cure in their
lifetime. Men commonly described feeling ‘‘infected’’ and reducing
this infectiousness was seen as a major benefit of ART; not purely to
reduce the risk of transmission to sexual partners but to facilitate
disclosure to partners, reduce anxiety and guilt and restore sexual
confidence commonly lost after HIV diagnosis. Having a long-term
HIV-negative partner was a strong facilitator to starting ART to
reduce transmission in the absence of good evidence of individual
health benefit.
Conclusions: Factors involved in the decision to start ART in PHI were
complex. Uncertainty over individual health benefits in conjunction
with fear of toxicities were barriers to starting ART early. By contrast
ART was seen as a facilitator to disclosure, and as a way to limit the
consequences of infection until a cure is found.
P201
The suspected unexpected and serious adverse events of
antiretroviral drugs used as HIV prophylaxis in HIV
uninfected persons
149
Poster Abstracts
Ewa Pietraszkiewicz; Ewa Firlag-Burkacka; Andrzej Horban and
Justyna D Kowalska
HIV Out-Patient Clinic, Hospital for Infectious Diseases, Warsaw,
Poland.
Introduction: With increased usage of antiretroviral drugs (ARVs) in
HIV uninfected persons proper reporting on suspected unexpected
serious adverse reactions (SUSARs) and continued insight into
serious adverse events (SAEs) is needed for adequate information
on ARVs safety in such populations.
Methods: We have evaluated medical documentation of persons
receiving ARVs after non-occupationally HIV exposure (nPEP) during
five concomitant years (20092013). SAEs and SUSARs were
evaluated by two HIV physicians and defined according to international standards. In statistical methods, Kaplan Meier survival
analysis was used to estimate the probability of SAE and Cox
proportional hazard models to identify independent predictors of
developing SAE. Only the first SAE was included in these analyses.
Results: In total, 375 persons received nPEP. The most common
reason was needle stick (43%), followed by unprotected sexual
intercourse (17%), rape (10%) and first aid (10%). In 84 (22%) cases,
the source patient was either known to be HIV positive or within a
high risk group (active injecting drug user). In total, 170 SAEs were
reported, 139 persons had only one SAE and majority developed it
within first two weeks. The most frequent first SAEs were gastrointestinal disorders (22%), followed by general symptoms (9%),
hypersensitivity reactions (1.6%) and CNS symptoms (1.3%). The
remaining events were laboratory abnormalities of liver and kidney
function, haematological disorders, other and unknown, each
contributing to less than 1% of all patients. 8 (2.1%) patients have
developed a SUSAR (bradycardia, vivid dreams, lymphadenopathy of
the neck, increased platelet count, swelling and pain of large joints,
swelling of lower limbs, peripheral oedema and loss of concentration). 22 (5.9%) persons discontinued nPEP due to adverse event and
19 (5.1%) required a paid sick leave from work. In multivariate
analyzes, only age was independent predictor of developing SAE (HR
1.17; [95% CI 1.031.34]; p0.02).
Conclusions: In our observation, SAEs in reaction to nPEP were
frequent yet usually mild events, mostly occurring in first two weeks
and rarely causing discontinuation. The only significant factor
increasing the risk of SAE was age. SUSARs were rare and moderately
significant. More insight into this important area is required in order
to ascertain proper pharmacovigilance of ARVs usage in HIV uninfected persons.
P202
Acceptability of PrEP among HIV negative Portuguese men
who have sex with men that attended 2014 Lisbon pride fair
Luı́s Miguel Rocha1; Maria José Campos1; João Brito1;
Ricardo Fuertes1; Jesus Rojas1; Nuno Pinto1; Luı́s Mendão2 and
Julio Esteves1
1
GAT Portugal, CheckpointLX, Lisboa, Portugal. 2GAT Portugal, Lisboa,
Portugal.
Introduction: Consistent use of PrEP reduces HIV transmission from
sexual practices amongst men who have sex with men (MSM) up to
92% [1]. Lisbon MSM cohort study estimates point that 59.3% of
their participants at entrance (1593 HIV negative MSM enrolled
between April 2011 and May 2013) were eligible for PrEP [2],
according to the 2014 USA PrEP guidelines [3]. Studies about PrEP
acceptability and implementation support policies aimed at increasing and rolling out its use. Hence, the exploratory study about PrEP
acceptability in MSM at Lisbon.
Material and Methods: A street-based intercept survey, adapted from
Mantell et al. study [4], was the one used on MSM attending the 2014
Lisbon pride fair. The survey included socio-demographic data, PrEP
awareness and readiness to use it, probability of MSM’s social network
Abstract P201Table 1. Cox proportional hazard models for the risk of developing first SAE
Univariate
Hazard ratio
Gender
Calendar year
Multivariate
95% CI
p
Hazard ratio
0.53
1.05
Female
1.00
Male
0.9
0.641.26
95% CI
p
0.731.50
0.81
1.00
2009
2010
0.79
0.471.34
0.38
0.76
0.441.31
0.33
2011
2012
0.90
1.24
0.511.60
0.781.97
0.72
0.36
0.86
1.11
0.471.56
0.671.84
0.62
0.68
0.62
2013
1.52
0.952.43
0.080
1.17
0.632.16
Per 5 years older
1.02
1.001.03
0.010
1.08
1.011.16
0.02
Per 10 years older
1.18
1.041.35
0.010
1.17
1.031.34
0.02
AZT/3TC
1.00
TDF/FTC
0.95
0.51/1.76
0.87
0.91
0.461.81
0.79
Regimen
2 ARVs
1.00
3 ARVs
Sexual
1.33
0.751.99
0.41
Exposure risk
Age
NRTI
Source patient HIV status
1.00
1.00
0.951.86
0.097
1.22
1.00
Needle stick
1.10
0.741.63
0.64
0.98
0.621.54
0.92
Other
0.82
0.521.29
0.38
0.80
0.491.32
0.39
Unknown
1.00
HIV infected or high risk
0.85
0.511.33
0.44
1.00
0.561.29
0.45
0.83
150
to also use it, promptness to join PrEP-related studies, type of PrEP
warranted and condomless anal sex practice in the last six months.
Results: A total of 110 HIV negative Portuguese MSM responded, with
a median age of 33% and 84% of them identified themselves as gay. A
majority of MSM were unaware of PrEP (59%); those that were aware,
had heard of it trough CheckpointLx (31%), internet (22%) or health
professionals (20%). 66% were likely or very likely to participate in
PrEP-related studies. 57% of MSM were likely or very likely to use PrEP
if available and reported that some, if not almost all of their social
network, will do it too (70%). Type of PrEP preferred was oral, a pill a
day (43%), followed by oral, intermittent intake (32%). Overall 41% of
MSM had condomless anal sex practice in the last six months.
Conclusions: In this MSM Portuguese sample, a general willingness
to adopt PrEP was predominant, specially the oral daily intake. Fortyone percent of participants had had condomless anal sex practice in
the last six months and therefore fitted within the criteria to be on
Pre-Exposure Prophylaxis (PrEP), according to MSM Risk Index in
2014 USA PrEP guidelines. PrEP, when available in Portugal, should
be a powerful tool for HIV prevention in this key population.
References
1. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L,
et al. iPrEx Study Team. Pre-exposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363(27):
258799.
2. Poster submitted and accepted to 20th International AIDS
Conference, code MOPE152.
3. CDC. PrEP for the prevention of HIV in the USA: a clinical practice
guideline. CDC: US Public Health Service; 2014. Available from:
http://www.cdc.gov/hiv/pdf/PrEPguidelines2014.pdf.
4. Mantell JE, et al. Knowledge and attitudes about PrEP among
sexually active men who have sex with men and who participate in
New York City Gay Pride Events. LGBT Health. June 2014;1(2):937.
Poster Abstracts
information about participants’ attitudes and preferences towards
TasP and PrEP. Collected data underwent framework analysis, allowing the development of overarching categories, sub-themes and
inductive interpretation.
Results: The majority of participants, irrespective of gender and HIV
status, found TasP more acceptable than PrEP. A key factor influencing this decision was HIV-negative participants’ limited motivation to take and adhere to antiretrovirals (ARVs), primarily due to
a predominantly external health locus of control, a lack of cultural
acceptance of prophylactic medication and concerns about side
effects. In addition to this, the likely health improvements TasP offers
HIV-positive partners, as well as the attitude that the sick individual
should be the first to receive HIV medication, also contributed to this
conclusion. Issues of risk compensation were raised, with some HIVnegative partners indicating a desire to stop using condoms if ARVbased prevention methods were available.
Conclusions: Findings from the study indicate that TasP may
represent a more viable approach to HIV prevention in Kenya than
PrEP. Couples’ preferences, however, may differ depending on local
attitudes towards prophylaxis and health locus of control.
References
1. Coburn BJ, Gerberry DJ, Blower S. Qualification of the role of
discordant couples in driving incidence of HIV in sub-Saharan Africa.
Lancet Infect Dis. 2011;11(4):2634.
2. Allen S, Meinzen-Derr J, Kautzman M, Zulu I, Trask S, Fideli U, et al.
Sexual behaviour of HIV discordant couples after HIV counselling and
testing. AIDS. 2003;17(5):73340.
3. Eisingerich AB, Wheelock A, Gomez GB, Garnett GP, Dybul MR,
Piot PK. Attitudes and acceptance of oral and parenteral HIV preexposure prophylaxis among potential user groups: a multinational
study. PLoS One. 2012;7(1):e28238.
4. Heffron R, Ngure K, Mugo N, et al. Willingness of Kenyan HIV-1
serodiscordant couples to use antiretroviral-based HIV-1 prevention
strategies. J Acquir Immune Defic Syndr. 2012;61(1):1169.
P203
Attitudes of serodiscordant couples towards antiretroviralbased HIV prevention strategies in Kenya: a qualitative
study
P204
Nikola Fowler1; Paul Arkell2; Michael Abouyannis3; Catherine James1
and Lesley Roberts4
1
College of Medical and Dental Sciences, University of Birmingham,
Birmingham, UK. 2Foundation Programme, West Midlands Deanery,
Birmingham, UK. 3Emergency Department, Stanger Provincial
Hospital, Stanger, South Africa. 4Primary Care Clinical Sciences,
University of Birmingham, Birmingham, UK.
Hsing-Chuan Li1; Yu-Ping Cheng2 and Chia-Jui Yang2
1
Department of Infection Control, Far Eastern Memorial Hospital,
New Taipei City, Taiwan. 2Department of Internal Medicine, Far
Eastern Memorial Hospital, New Taipei City, Taiwan.
Introduction: Transmission in serodiscordant couples (SDCs) accounts for approximately half of all new HIV infections, both in
Kenya and the wider sub-Saharan region [1]. With evidence to
suggest inconsistent condom use within this population [2], the
World Health Organization has recommended two new methods of
HIV prevention for SDCs: Treatment as Prevention (TasP) and PreExposure Prophylaxis (PrEP). However, there has been little research
about the attitudes of SDCs towards these strategies [3,4]; knowledge that is paramount for successfully predicting the acceptability
and efficacy of each method, as well as for informing decisions
regarding HIV policy changes in Kenya.
Methods: An exploratory, qualitative study was conducted in the
Muhoroni constituency of Nyando district, Kenya from January to
March 2013. Purposive sampling was predominately used to recruit
21 HIV-positive and 17 HIV-negative individuals in a serodiscordant
relationship from four hospitals and health centres. During face-toface semi-structured interviews, topic guides were used to elicit
Safety, tolerability and effectiveness of HIV
non-occupational prophylaxis in Taiwan
Introduction: Increasing numbers of new HIV infection is an important issue of public health in Taiwan. We aim to evaluate the
safety, tolerability and effectiveness of HIV non-occupational prophylaxis (nPEP) in Taiwan.
Materials and Methods: We conducted a prospective cohort observational study between March 2011 and May 2014. Three-combined
antiretroviral agents were prescribed for all the persons who sought
for HIV post-exposure prophylaxis after high risk sexual behaviour.
HIV screening, health education and consultation were done before
initiation of nPEP. Adverse effects were evaluated at Weeks 1, 2 and
4 and effectiveness was evaluated at Weeks 12 and 24. We also
assessed adherence by pill count and regimen completion rates.
Results: During the study periods, 255 persons were enrolled.
Among the enrolled cases, 43.9% (112/255) of them received
zidovudine (AZT)-based regimen while the others received tenofovir
(TDF)-based regimen and the third agent was composed of mostly
lopinavir/ritonavir (81.4%). The completion rate of nPEP was 85.9%
(219/255), and discontinuation rate of nPEP among AZT-based
regimen is higher than TDF-based regimen (17.0% vs 8.2%). Any
grade adverse effects are higher among AZT-based regimen than
151
Poster Abstracts
TDF-based regimen (62.5% vs 32.1%) although most adverse effects
were grade 12. After a 24-week follow-up, only one person experienced HIV seroconversion and he had primary syphilis at the
moment when he sought for nPEP.
Conclusions: NPEP could be an effective prevention method in a part
of HIV prevention strategy and TDF-based regimen had better
tolerability in Taiwan.
RESISTANCE
P205
Detection of resistance mutations and CD4 slopes in
individuals experiencing sustained virological failure
Anna Schultze1; Roger Paredes2; Caroline Sabin1; Andrew N Phillips1;
Deenan Pillay1; Ole Kirk3; Jens D Lundgren3; Anton Pozniak4;
Anton Pozniak4; Mark Nelson4 and Alessandro Cozzi-Lepri1 on behalf
of Eurosida in Eurocoord
1
London, London, UK. 2Hospital Universitari Germans Trias i Pujol,
Universitat Autònoma de Barcelona, Fundacions irsiCaixa i Lluita
contra la SIDA, Badalona, Spain. 3CHIP, Department of Infectious
Diseases, Rigshospitalet, University of Copenhagen, Copenhagen,
Denmark. 4HIV and Sexual Health Kobler Clinic, Chelsea and
Westminster Hospital, London, UK. 5CHIP, Department of Infectious
Diseases, Rigshospitalet, University of Copenhagen, Copenhagen,
Denmark.
Introduction: Several resistance mutations have been shown to
affect viral fitness, and the presence of certain mutations might
result in clinical benefit for patients kept on a virologically failing
regimen due to an exhaustion of drug options. We sought to quantify
the effect of resistance mutations on CD4 slopes in patients
undergoing episodes of viral failure.
Materials and Methods: Patients from the EuroSIDA and UK CHIC
cohorts undergoing at least one episode of virological failure (3
consecutive RNA measurements 500 on ART) with at least three
CD4 measurements and a resistance test during the episode were
included. Mutations were identified using the IAS-US (2013) list,
and were presumed to be present from detection until the end
of an episode. Multivariable linear mixed models with a random
intercept and slope adjusted for age, baseline CD4 count, hepatitis
C, drug type, RNA (log-scale), risk group and subtype were used
to estimate CD4 slopes. Individual mutations with a population prevalence of 10% were tested for their effect on the CD4 slope.
Results: A total of 2731 patients experiencing a median of 1 (range
14) episodes were included in this analysis. The prevalence of
any resistance per episode was 88.4%; NNRTI resistance was most
common (78.5%). Overall, CD4 counts declined by 17.1 ( 19.7;
14.5) cells per year; this decline was less marked with partial viral
suppression (current HIV RNA more than 1.5 log below the setpoint;
Abstract P205Table 1. The effect of class-specific mutations
among individuals with 1 detected resistance mutation
Comparison
NRTI vs no NRTI
NNRTI vs no NNRTI
PI vs no PI
Difference in CD4 Slope (95% CI)
p
12.63 (1.9423.32)
5.77 (11.990.45)
0.02
0.07
0.73 ( 4.986.43)
0.75
p0.01). In multivariable models adjusting for viral load, CD4 decline was slower during episodes with detected resistance compared
to episodes without detected resistance (21.0 cells/year less, 95% CI
11.7530.31, pB0.001). Among those with more than one resistance mutation, there was only weak evidence that class-specific
mutations had any effect on the CD4 slope (Table 1). The effects of
individual mutations (incl. M184V) were explored, but none were
significantly associated with the CD4 slope; for these comparisons, a
Bonferroni-corrected p-value level was 0.003.
Conclusions: In our study population, detected resistance was associated with slightly less steep CD4 declines. This may be due to a
biological effect of resistance on CD4 slopes, or other unmeasured
factors such as poor adherence among individuals without resistance. Among individuals with detected drug resistance, we found no
evidence suggesting that the presence of individual mutations was
associated with beneficial CD4 slope changes.
P206
HIV-1 group O integrase displays lower susceptibility to
raltegravir and has a different mutational pathway for
resistance than HIV-1 group M
Agnès Depatureaux; Thibault Mesplède; Peter Quashie;
Maureen Oliveira; Daniela Moisi; Bluma Brenner and Mark Wainberg
McGill AIDS Center, Lady Davis Institute for Medical Research, Jewish
General Hospital, Montreal, Canada
Introduction: HIV-1 group O (HIV-O) is a rare HIV-1 variant
characterized by a high number of polymorphisms, especially in
the integrase gene, e.g. positions L74I, S153A, G163Q and T206S. As
HIV-O integrase enzymes have not previously been studied, our aim
was to assess the impact of HIV-O integrase polymorphisms on
susceptibility to integrase inhibitors and emergence of resistance
associated mutations.
Viruses and Methods: We cloned and purified integrase proteins
from each of HIV-1 Group O clades A (HIV-O/A) and B (HIV-O/B), a
HIV-O divergent strain (HIV-O/Div), and HIV-1 group M (subtype B,
HIV-M/B) and characterized these enzymes for susceptibility to
integrase strand transfer inhibitors (INSTIs) in cell-free assays and in
tissue culture, in the absence or presence of varying concentrations
of several INSTIs. The inhibition constant (Ki) and IC50 were
calculated and compared for HIV-M and HIV-O integrases. Selections
for resistance-related mutations were performed using cord blood
mononuclear cells and increasing concentration of INSTIs.
Results: HIV-O integrase and viruses were more susceptible to
raltegravir (RAL) in competitive inhibition assays and in tissue culture
than were HIV-M enzymes and viruses, respectively. During selection,
we observed different pathways of resistance depending on the drug
and clade. Mutations selected in HIV-O can be classified as follows:
(1) mutations described for HIV-M such as T97A, Q148R, V151A/I
(RAL), T66I, E92Q, E157Q (EVG) and M50I, R263K (DTG) and (2)
signature mutations for HIV-O (i.e. not described in HIV-M) F121C
(HIV-O/B for RAL), V75I (HIV-O/A for RAL) and S153V (HIV-O/A for
DTG). Only the HIV-O/Div selected the Q148R mutation for RAL
and R263KM50I for DTG, as previously described for HIV-M.
None of the HIV-O viruses selected either N155H or Y143C. The
selection of the specific S153V mutation could be explained at the
nucleotide level: HIV-O at this position contains an alanine and
substitution of alanine to valine (153AGGC 0153VGTC) is easier
than substitution of alanine to tyrosine (153AGGC0153YTAC), with
only a transversion needed instead of one transition plus one
transversion.
Conclusion: This is the first report of susceptibility and resistance in
vitro to INSTIs for HIV-O. Our study confirmed the impact of HIV-O
152
Poster Abstracts
polymorphism, on susceptibility to INSTIs and the emergence of
resistance mutations.
P207
Protease mutations emerging on darunavir in protease
inhibitor-naı̈ve and experienced patients in the UK
Kate El Bouzidi1; Ellen White2; Jean L Mbisa3; Andrew Phillips4;
Nicola Mackie5; Anton Pozniak6 and David Dunn7
1
Department of Virology, University College London, London, UK.
2
MRC Clinical Trials Unit, Medical Research Council, London, UK.
3
Antiviral Unit, Public Health England, London, UK. 4Infection &
Population Health, University College London, London, UK. 5Imperial
College Healthcare NHS Trust, Jefferiss Wing, St Mary’s Hospital,
London, UK. 6HIV and Sexual Health, Chelsea & Westminster Hospital
NHS Trust, London, UK. 7MRC Clinical Trials Unit, University College
London, London, UK.
Introduction: Darunavir (DRV) is a preferred agent in treatment guidelines for ART-naı̈ve and experienced patients [1]. It is considered
to have a high genetic barrier to resistance and 11 resistanceassociated mutations (RAMs) are recognized by IAS-USA [2]. These
have largely been identified by analyses examining the correlation
between baseline genotype and virological response [3]. However,
there is little information on RAMs that are directly selected by DRV,
outside of short-term clinical trials. We aimed to identify emerging
mutations by comparing the genotypes of individuals before and
after DRV exposure.
Materials and Methods: The UK HIV Drug Resistance Database was
used to identify patients aged over 16 who had received at least 30
days of a DRV-containing regimen. Patients were included if they had
a ‘‘baseline’’ resistance test, prior to DRV exposure, and a ‘‘repeat’’
test, either on DRV or within 30 days of stopping this agent. To avoid
attributing the effects of other PIs on emerging RAMs to DRV,
patients were excluded if they had received another PI for greater
than 90 days between the baseline genotype and the start of DRV.
mutations
IAS-USA DRV
mutation
11I
32I
Baseline and emerging IAS-USA DRV
The baseline and repeat tests were compared to determine the
nature of mutations stratified by PI history.
Results: A total of 5623 patients had DRV, of whom 306 met the
inclusion criteria. A total of 228 (74.5%) were male, median age at
the start of DRV was 42 years (IQR 3747), and half had subtype B
infection. The mode of transmission was homosexual contact for
50%, heterosexual for 38%, and 3% were injection drug users. The
median CD4 count at the start of DRV was 257 cells/mm3 (IQR 94
453). A total of 149 patients (49%) had a history of PI use prior to
DRV, and 157 (51%) were PI-naı̈ve. The most common previous PIs
were lopinavir, atazanavir, and saquinavir. Baseline DRV RAMs were
present in 1 (0.6%) PI-naı̈ve and 20 (13.4%) PI-experienced patients.
Mutations emerged under DRV pressure in a further 3 (1.9%) PInaı̈ve patients, and in 7 (4.7%) PI-experienced patients, 5 of whom
had other DRV RAMs present at baseline (Table 1). The median time
from the start of DRV to the repeat test was 196 days for PI-naı̈ve
patients and 296 days for PI-experienced.
Conclusions: PI-experienced patients had a greater prevalence of
DRV RAMs at baseline than PI-naı̈ve individuals, probably due to the
fact that some DRV RAMs can be selected by other PIs. This group
also accumulated more RAMs during DRV exposure, possibly because
previous PIs had caused minority variants which then emerged on
DRV therapy. Overall, only 10 patients accumulated 16 RAMs, which
supports the perception that DRV has a high genetic barrier to
resistance. Repeat genotyping in the case of virological failure on
DRV may still be warranted to detect emerging resistance and guide
management decisions.
References
1. British HIV Association guidelines for the treatment of HIV-1 positive adults with antiretroviral therapy 2012. HIV Med. 2014;15(Suppl.
1):185.
2. Johnson VA, Calvez V, Gunthard HF, Paredes R, Pillay D, Shafer RW,
et al. Update of the drug resistance mutations in HIV-1: March 2013. Top
Antivir Med. 2013;21(1):614.
3. Libre JM, Imaz A, Clotet B. From TMC114 to Darunavir: five years
of data on efficacy. AIDS Rev. 2013;15:11221.
P208
Rilpivirine versus etravirine validity in NNRTI-based
treatment failure in Thailand
PI-naive
PI-experienced
(n 157 patients)
(n 149 patients)
Baseline
Emerged
Baseline
Emerged
(n)
(n)
(n)
(n)
0
0
0
1
1
1
2
3
33F
0
0
11
2
47V
0
0
2
0
50V
0
0
1
0
54L
0
0
2
2
54M
0
0
0
0
74P
1
0
1
0
76V
84V
0
0
1
1
5
12
2
1
89V
0
0
4
1
Total mutations
1
3
40
13
Total patients
1
3
20
7
Phairote Teeranaipong1; Sunee Sirivichayakul2;
Suwanna Mekprasan2; Kiat Ruxrungtham2 and Opass Putcharoen3
1
Department of Parasitology, Faculty of Medicine, King
Chulalongkorn Memorial Hospital, Chulalongkorn University,
Bangkok, Thailand. 2Division of Allergy and Clinical Immunology, King
Bangkok, Thailand. 3Division of Infectious Diseases, King
Bangkok, Thailand.
Introduction: Etravirine (ETR) and rilpivirine (RPV) are the secondgeneration non-nucleoside reverse transcriptase inhibitors (NNRTI)
for treatment of HIV-1 infection. Etravirine is recommended for
patients with virologic failure from first generation NNRTI-based
regimen [1]. RPV has profile with similar properties to ETR but this
agent is approved for treatment-naı̈ve patients [2]. In Thailand, ETR is
approximately 45 times more expensive than RPV. We aimed to study
the patterns of genotypic resistance and possibility of using RPV in
patients with virologic failure from two common NNRTI-based
regimens: efavirenz (EFV)- or nevirapine (NVP)-based regimen.
Materials and Methods: Data of clinical samples with confirmed
virologic failure during 20032010 were reviewed. We selected
the samples from patients who failed EFV- or NVP-based regimen.
153
Resistance-associated mutations (RAMs) were determined by IASUSA Drug Resistance Mutations. DUET, Monogram scoring system
and Stanford Genotypic Resistance Interpretation were applied to
determine the susceptibility of ETR and RPV.
Results: A total of 2086 samples were analyzed. Samples from 1482
patients with virologic failure from NVP-based regimen treatment
failure (NVP group) and 604 patients with virologic failure from EFVbased regimen treatment failure (EFV group) were included. 95%
of samples were HIV-1 CRF01_AE subtype. Approximately 80% of
samples in each group had one to three NNRTI-RAMs and 20% had
four to seven NNRTI-RAMs. 181C mutation was the most common
NVP-associated RAM (54.3% vs 14.7%, pB0.01). 103N mutation was
the most common EFV-associated RAM (56.5% vs 19.1%, p B0.01).
The calculated scores from all three scoring systems were concordant. In NVP group, 165 (11.1%) and 161 (10.9%) patients were
susceptible to ETR and RPV, respectively (p0.81). In EFV group, 195
(32.2%) and 191 (31.6%) patients were susceptible to ETR and RPV,
respectively (p 0.81). The proportions of viruses that remained
susceptible to ETR and RPV in EFV group were significantly higher
than NPV group (ETR susceptibility 32.2% vs 11.1%, pB0.01, RPV
susceptibility 31.6% vs 10.9%, p B0.01), respectively.
Conclusions: RPV might be a cost saving and reasonable second line
NNRTI for patients who failed EFV- or NVP-containing regimens,
especially in resource-limited setting because these two agents have
comparable susceptibility identified by genotyping. From our study,
approximately 30% of patients who failed EFV-based regimens had
viruses that remained susceptible to RPV.
References
1. Adolescents PoAGfAa. Guidelines for the use of antiretroviral
agents in HIV-1-infected adults and adolescents: Department
of Health and Human Services; 2013 [updated May 1, 2014; cited
July 10, 2014]. Available from: http://aidsinfo.nih.gov/ContentFiles/
AdultandAdolescentGL.pdf.
2. US Food and Drug Administration. Approval of Edurant (rilpivirine)
a new NNRTI for the treatment of HIV in treatment naive patients.
2011 [cited 2014 July 10]. Available from: http://www.fda.gov/
ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/
ucm256151.htm.
P209
Appearance of NS3 Q80K mutation in HCV genotype 1a
mono- or HIV/HCV co-infected patients in a Berlin
laboratory
Robert Ehret1; Stefan Neifer2; Hauke Walter1; Axel Baumgarten3 and
Martin Obermeier1
1
Laboratory, MIB, Berlin, Germany. 2Laboratory, Medical Laboratory
Neifer, Berlin, Germany. 3Out Patients Clinic, MIB, Berlin, Germany.
Introduction: Simeprevir, a new oral NS3/4A protease inhibitor, was
recently approved by the FDA and the EMA for the treatment of
patients with chronic HCV genotype 1, 4, 5 and 6 infection l. It has
been recommended in the 2014 UK Consensus Guidelines as a
possible treatment of previously untreated genotype 1a-infected
patients. The antiviral efficacy of simeprevir is adversely affected by
the mutation at the Q80K loci. There is controversial discussion that
the incidence of Q80K in the European HCV 1a-infected community is
very low and therefore testing of Q80K before starting a therapy
including simeprevir is not necessary. We analyzed the appearance of
Q80K in all sequenced HCV NS3A samples in 2014 in our laboratory.
Materials and Methods: All in 2014 received orders for HCV
resistance tests were analyzed with an in-house bulk sequencing
method analyzing NS3A amino acids 1181. Analysis was performed
Poster Abstracts
using geno2pheno HCV. The genotype 1a samples were selected,
Q80K status and data of HIV co-infection were collected.
Results: Forty-two HCV 1a samples were sent to us for resistance
analyses from nine different medical centres in Berlin and Hannover,
Germany. Nineteen (or 45%) of the sequences showed a Q80K
mutation. Six extra clade I viruses had no Q80K mutation. Comparison between mono- and HIV-1 co-infected patients showed no
difference in frequency of Q80K (mono-infected: 8 out of 19 patients;
co-infected: 9 out of 23). For two 80K-positive patients, the HIVstatus was not available.
Conclusions: The incidence for Q80K mutation in HCV genotype 1a
with overall 45% is substantially high in our cohort and does
not differ between mono- and HIV-1 co-infected patients. Response
to simeprevir is affected by the presence of viral Q80K. When
treating HCV-infected patients with a simeprevir containing regimen,
it is therefore important that HCV does not contain the Q80K
mutation.
P210
Patterns of drug resistance among newly diagnosed HIV-1
infected patients in Greece during the last decade: the
crucial role of transmission networks
Dimitrios Paraskevis1; Assimina Zavitsanou1;
Emmanouil Magiorkinis1; Panagiotis Gargalianos2;
Georgios Xylomenos2; Marios Lazanas3; Maria Chini3;
Athanasios Skoutelis4; Vasileios Papastamopoulos4;
Anastasia Antoniadou5; Antonios Papadopoulos5; Mina Psichogiou6;
Georgios Daikos6; Alexis Vassilakis1; Georgios Chrysos7;
Vasilis Paparizos8; Soa Kourkounti8; Helen Sambatakou9;
Theodoros Kordossis10; Georgios Koratzanis11;
Periklis Panagopoulos12; Evangelos Maltezos12; Stylianos Drimis7 and
Angelos Hatzakis1
1
Hygiene Epidemiology and Medical Statistics, Medical School,
University of Athens, Athens, Greece. 2Department of Internal
Medicine, G. Gennimatas General Hospital, Athens, Greece.
3
Department of Internal Medicine, Hellenic Red Cross Hospital,
Athens, Greece. 4Department of Medicine and Infectious Diseases,
Evangelismos General Hospital, Athens, Greece. 5Department of
Internal Medicine, University General Hospital Attikon, Athens,
Greece. 6Department of Propedeutic Medicine, Laiko General
Hospital, Athens, Greece. 7Department of Internal Medicine, Tzaneio
General Hospital, Piraeus, Greece. 8Department of Dermatology, A.
Syngros Hospital, Athens, Greece. 9Infectious Diseases, Ippokrateion
General Hospital, Athens, Greece. 10Department of Pathophysiology,
Laiko General Hospital, Athens, Greece. 11Infectious Diseases,
Sismanogleio General Hospital, Athens, Greece. 12Department of
Internal Medicine, Democritus University of Thrace, Alexandroupolis,
Greece.
Introduction: The prevalence of drug resistance is approximately 10%
in Europe and North America among newly infected patients. We aim
to investigate the temporal patterns of resistance among drug naive
HIV-infected individuals in Greece and also to determine transmission networking among those with resistant strains.
Materials and Methods: Protease (PR) and partial reverse transcriptase (RT) sequences were determined from 2499 newly diagnosed
HIV-1 patients, in Greece, during 20032013. Genotypic drug resistance was estimated using the HIVdb: Genotypic Resistance Interpretation Algorithm. We identified transmission clusters of resistant
strains on the basis of a large collection of HIV-1 sequences from
4024 seropositives in Greece. Phylodynamic analysis was performed
using a Bayesian method.
154
Poster Abstracts
break among drug injectors in Athens metropolitan area: a longitudinal study. PLoS One. 2013;8(11):e78941.
P211
Improved therapy-success prediction with GSS estimated
from clinical HIV-1 sequences
Alejandro Pironti1; Nico Pfeifer1; Rolf Kaiser2; Hauke Walter3 and
Thomas Lengauer1
1
Computational Biology and Applied Algorithmics, Max Planck
Institute for Informatics, Saarbrücken, Germany. 2Department of
Clinical Virology, University of Cologne, Cologne, Germany.
3
Diagnostics, Medizinisches Infektiologiezentrum Berlin, Berlin,
Germany.
Phlodynamics of 103N.
Results: We estimated drug resistance levels among naı̈ve patients
on the basis of all resistance mutations in PR and partial RT.
The overall prevalence of resistance was 19.6% (490/2499). Resistance to NNRTIs was the most common (397/2499, 15.9%) followed
by PIs (116/2499, 4.6%) and NRTIs (79/2499, 3.2%). We found a
significant trend for decreasing resistance to NRTIs over time (6.7%
1.6%). There was no time trend for the overall PI and NNRTI
resistance. The most frequently observed major resistant sites in
PR were V82 (2.0%) and L90 (1.8%). In RT, we found E138 (58.6%),
K103 (13.1%), V179 (8.4%) and T215 (7.1%), M41 (4.7%) associated
with resistance to NNRTIs and NRTIs, respectively. The prevalence
of K103N and E138Q were significantly increased during
20032013. Crucially, we found that both K103N, E138Q are
associated with transmission networking within men having sex
with men (MSM) and intravenous drug user (IDU) local networks.
The K103N network included seropositives across Greece, while
the latter only from the recent IDU outbreak in Athens metropolitan
area (1). Phylodynamic analyses revealed that the exponential
growth for K103N network started in 2009 (Figure 1) and for the
E138Q in 2010.
Conclusions: The overall resistance has been stable in Greece over
time; however, specific NNRTI resistance patterns are increasing.
Notably, they are associated with local transmission networking, thus
suggesting that this is the cause for the increased patterns of NNRTI
resistance and not multiple transmissions of resistant strains from
different sources among treated individuals. Our study highlights the
advance of molecular epidemiology for understanding the dynamics of
resistance.
Reference
1. Paraskevis D, Nikolopoulos G, Fotiou A, Tsiara C, Paraskeva D,
Sypsa V, et al. Economic recession and emergence of an HIV-1 out-
Introduction: Rules-based HIV-1 drug-resistance interpretation (DRI)
systems disregard many amino-acid positions of the drug’s target
protein. The aims of this study are (1) the development of a drugresistance interpretation system that is based on HIV-1 sequences
from clinical practice rather than hard-to-get phenotypes, and (2) the
assessment of the benefit of taking all available amino-acid positions
into account for DRI.
Materials and Methods: A dataset containing 34,934 therapy-naı̈ve
and 30,520 drug-exposed HIV-1 pol sequences with treatment history
was extracted from the EuResist database and the Los Alamos
National Laboratory database. 2,550 therapy-change-episode baseline sequences (TCEB) were assigned to test set A. Test set B contains
1,084 TCEB from the HIVdb TCE repository. Sequences from patients
absent in the test sets were used to train three linear support vector
machines to produce scores that predict drug exposure pertaining to
each of 20 antiretrovirals: the first one uses the full amino-acid
sequences (DEfull), the second one only considers IAS drug-resistance
positions (DEonlyIAS), and the third one disregards IAS drug-resistance
positions (DEnoIAS). For performance comparison, test sets A and B
were evaluated with DEfull, DEnoIAS, DEonlyIAS, geno2pheno[resistance],
HIVdb, ANRS, HIV-GRADE, and REGA. Clinically-validated cut-offs were
used to convert the continuous output of the first four methods
into susceptible-intermediate-resistant (SIR) predictions. With each
method, a genetic susceptibility score (GSS) was calculated for each
therapy episode in each test set by converting the SIR prediction for
its compounds to integer: S2, I1, and R0. The GSS were used
to predict therapy success as defined by the EuResist standard datum
definition. Statistical significance was assessed using a Wilcoxon
signed-rank test.
Results: A comparison of the therapy-success prediction performances among the different interpretation systems for test set A can
be found in Table 1, while those for test set B are found in Figure 1.
Therapy-success prediction of first-line therapies with DEnoIAS
performed better than DEonlyIAS (p B1016).
Abstract P211Table 1. Performance comparison for therapy-success prediction in test set A, quantified via area under the receiver
operating characteristic curve (AUC)
DEfull
DEonlyIAS
DEnoIAS
HIVdb
ANRS
GRADE
REGA
geno2pheno[resistance]
All first-line therapies
0.54
0.52
0.6
0.51
0.51
0.5
0.52
0.53
First-line therapies with TDR
First-line therapies without TDR
0.64
0.51
0.58
0.5
0.69
0.58
0.48
0.5
0.54
0.5
0.46
0.5
0.53
0.51
0.5
0.52
Therapies on pretreated patients
0.68
0.69
0.59
0.68
0.67
0.69
0.69
0.69
All
0.67
0.67
0.65
0.66
0.65
0.66
0.66
0.66
155
Poster Abstracts
KVXATV/r (n 4), the emerging mutations observed were RT
M184V (n 2; 50%) and no Pro mutation. Most of patients retained
virus predicted to be susceptible to all antiretrovirals (22 virus
became resistant to 3TC/FTC and three became resistant to ATV).
None of them became resistant to DRV.
Conclusions: Among 1,518 patients in routine care who started their
first line treatment with DRV/r or ATV/r, very few of them (1.4%)
selected resistance mutations at failure with three patients selecting
an ATV resistant virus. None of them became resistant to DRV. The
less frequent follow-up of patients in routine care compared to
clinical trials does not impact the resistance selection rate in patients
treated by boosted DRV or ATV based regimen.
P213
Viral escape in the CNS with multidrug-resistant HIV-1
Abstract P211Figure 1. Performance comparison for therapysuccess prediction in test set B.
Conclusions: Therapy success prediction benefits from the consideration of all available mutations. The increase in performance was largest in first-line therapies with transmitted drug-resistance mutations.
P212
Less frequent follow-up in routine care than in trials does
not impact resistance selection in patients failing DRV/r or
ATV/r first line treatment
Anne-Genevieve Marcelin1; Charlotte Charpentier2; Marc Wirden1;
Diane Descamps2 and Vincent Calvez1
1
Virology, Pitie-Salpetriere Hospital, Paris, France. 2Virology, BichatClaude Bernard Hospital, Paris, France.
Introduction: Selection of resistance mutations on antiretroviral
therapy (ART) including darunavir (DRV/r) or atazanavir (ATV/r) has
been reported infrequently but mainly in clinical trials where patients
were followed very frequently (at least four to five clinical visits and
viral load measurements per year). The aim of this study was to
evaluate the rate of resistance at failure and mutational patterns
emerging in patients receiving DRV/r or ATV/r based-regimen as first
line treatment and followed in standard clinical practice with less
clinical visits and viral load measurements (median 2 per year).
Methods: We studied 1,518 patients starting their first line antiretroviral therapy and followed during at least two years (n
799 TVDDRV/r, n70 KVXDRV/r, n618 TVDATV/r, n31
KVXATV/r). The median viral load at baseline was 76,000 copies/
mL and the median CD4 cell count 384 cell/mm3. Virological failure was defined as two consecutive viral load50 copies/mL
after previous suppression B50 copies/mL, or failure to achieve
B50 copies/mL. Predicted susceptibility was determined using the
last ANRS algorithm.
Results: Among the 1,518 patients, 193 (12.7%) failed during the two
years of follow-up. Among patients failing TVDDRV/r (n 95), the
emerging mutations observed were RT M184V (n 8; 8%) and Pro
V32I (n1; 1%). Among patients failing KVXDRV/r (n 8), the
emerging mutations observed were RT M184V (n 3; 37%) and Pro
I47V (n 1; 12%). Among patients failing TVDATV/r (n 86),
the emerging mutations observed were RT M184V (n 9; 10%), Pro
N88S (n 2; 2%) and Pro I50L (n 1; 1%). Among patients failing
Charles Béguelin1; Miriam Vázquez1; Manuel Bertschi2; Sabine Yerly3;
Denise de Jong4; Andri Rauch1 and Alexia Cusini1
1
Department of Infectious Diseases, University Hospital and
University of Bern, Bern, Switzerland. 2Department of Neurology,
University Hospital and University of Bern, Bern, Switzerland.
3
Laboratory of Virology, Geneva University Hospital, Geneva,
Switzerland. 4Department of Neuropsychology, University Hospital
and University of Bern, Bern, Switzerland.
Introduction: HIV-1 viral escape in the cerebrospinal fluid (CSF)
despite viral suppression in plasma is rare [1,2]. We describe the
case of a 50-year-old HIV-1 infected patient who was diagnosed with
HIV-1 in 1995. Antiretroviral therapy (ART) was started in 1998 with a
CD4 T cell count of 71 cells/ı̀L and HIV-viremia of 46,000 copies/mL.
ART with zidovudine (AZT), lamivudine (3TC) and efavirenz achieved
full viral suppression. After the patient had interrupted ART for two
years, treatment was re-introduced with tenofovir (TDF), emtricitabin
(FTC) and ritonavir boosted atazanavir (ATVr). This regimen suppressed HIV-1 in plasma for nine years and CD4 cells stabilized
around 600 cells/ı̀L. Since July 2013, the patient complained about
severe gait ataxia and decreased concentration.
Materials and Methods: Additionally to a neurological examination,
two lumbar punctures, a cerebral MRI and a neuropsycological test
were performed. HIV-1 viral load in plasma and in CSF was quantified
using Cobas TaqMan HIV-1 version 2.0 (Cobas Ampliprep, Roche
diagnostic, Basel, Switzerland) with a detection limit of 20 copies/mL.
Drug resistance mutations in HIV-1 reverse transcriptase and
protease were evaluated using bulk sequencing.
Results: The CSF in January 2014 showed a pleocytosis with 75 cells/
ı̀L (100% mononuclear) and 1,184 HIV-1 RNA copies/mL, while HIV-1
in plasma was below 20 copies/mL. The resistance testing of the CSFHIV-1 RNA showed two NRTI resistance-associated mutations
(M184V and K65R) and one NNRTI resistance-associated mutation
(K103N). The cerebral MRI showed increased signal on T2-weighted
images in the subcortical and periventricular white matter, in the
basal ganglia and thalamus. Four months after ART intensification
with AZT, 3TC, boosted darunavir and raltegravir, the pleocytosis in
CSF cell count normalized to 1 cell/ı̀L and HIV viral load was
suppressed. The neurological symptoms improved; however, equilibrium disturbances and impaired memory persisted. The neuropsychological evaluation confirmed neurocognitive impairments in
executive functions, attention, working and nonverbal memory, speed
of information processing, visuospatial abilities and motor skills.
Conclusions: HIV-1 infected patients with neurological complaints
prompt further investigations of the CSF including measurement
of HIV viral load and genotypic resistance testing since isolated
replication of HIV with drug resistant variants can rarely occur
despite viral suppression in plasma. Optimizing ART by using drugs
156
with improved CNS penetration may achieve viral suppression in CSF
with improvement of neurological symptoms.
References
1. Canestri A, Lescure FX, Jaureguiberry S, Moulignier A, Amiel C,
Marcelin AG, et al. Discordance between cerebral spinal fluid and
plasma HIV replication in patients with neurological symptoms who
are receiving suppressive antiretroviral therapy. Clin Infect Dis.
2010;50:7738.
2. Edén A, Fuchs D, Hagberg L, Nilsson S, Spudich S, Svennerholm B, et al.
HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive
antiretroviral treatment. J Infect Dis. 2010;202(12):181925.
P214
Characterization of natural polymorphic sites of the HIV-1
integrase before the introduction of HIV-1 integrase
inhibitors in Germany
Karolin Meixenberger1; Kaveh Pouran Yousef2; Sybille Somogyi1;
Stefan Fiedler3; Barbara Bartmeyer4; Max von Kleist2 and
Claudia Kücherer1
1
HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany.
2
Department of Mathematics and Computer Science, Freie Universität
Berlin, Berlin, Germany. 3Nosocomial Pathogens and Antibiotic
Resistances, Robert Koch Institute, Berlin, Germany. 4HIV/AIDS, STI and
Blood-borne Infections, Robert Koch Institute, Berlin, Germany.
Introduction: The aim of our study was to analyze the occurrence
and evolution of HIV-1 integrase polymorphisms during the HIV-1
epidemic in Germany prior to the introduction of the first integrase
inhibitor raltegravir in 2007.
Material and Methods: Plasma samples from drug-naı̈ve HIV-1
infected individuals newly diagnosed between 1986 and 2006 were
used to determine PCR-based population sequences of the HIV-1
integrase (amino acids 1278). The HIV-1 subtype was determined
using the REGA HIV-1 subtyping tool. We calculated the frequency of
amino acids at each position of the HIV-1 integrase in 337 subtype B
strains for the time periods 19861989, 19911994, 19951998,
19992002, and 20032006. Positions were defined as polymorphic
if amino acid variation was 1% in any period. Logistic regression
was used to identify trends in amino acid variation over time.
Resistance-associated mutations were identified according to the IAS
2013 list and the HIVdb, ANRS and GRADE algorithms.
Results: Overall, 56.8% (158/278) amino acid positions were polymorphic and 15.8% (25/158) of these positions exhibited a significant
trend in amino acid variation over time. Proportionately, most polymorphic positions (63.3%, 31/49) were detected in the N-terminal zinc
finger domain of the HIV-1 integrase. Motifs and residues essential for
HIV-1 integrase activity were little polymorphic, but within the minimal
non-specific DNA binding region I220-D270 up to 18.1% amino acid
variation was noticed, including four positions with significant amino acid
variation over time (S230, D232, D256, A265). No major resistance
mutations were identified, and minor resistance mutations were rarely
observed without trend over time. E157Q considered by HIVdb, ANRS,
and GRADE algorithms was the most frequent resistance-associated
polymorphism with an overall prevalence of 2.4%.
Conclusions: Detailed knowledge of the evolutionary variation of
HIV-1 integrase polymorphisms is important to understand the
development of resistance in the presence of the drug. Our results
will contribute to define the relevance of integrase polymorphisms in
HIV-strains resistant to integrase inhibitors and to improve resistance
interpretation algorithms.
Poster Abstracts
P215
Transmitted antiretroviral drug resistance in treatment
naı̈ve HIV-infected persons in London in 2011 to
2013
Katie McFaul1; Charlotte Lim1; Rachael Jones2; David Asboe3;
Anton Pozniak3; Sonali Sonecha3; Marta Boffito3 and
Nneka Nwokolo1
1
Chelsea and Westminster Hospital, London, UK. 2West London
Centre for Sexual Health, Chelsea and Westminster Hospital,
London, UK. 3Kobler Clinic, Chelsea and Westminster Hospital,
London, UK.
Introduction: Previously published UK data on HIV transmitted drug
resistance (TDR) shows that it ranges between 3 and 9.4% [1,2].
However, there are no recent data from populations where HIV
transmission rates are increasing. The aim of this study was to assess
the prevalence of TDR in untreated HIV-infected individuals attending
three HIV specialist clinics under the HIV Directorate, Chelsea and
Westminster Hospital and based throughout London the Kobler
Clinic, 56 Dean Street and West London Centre for Sexual Health.
Methods: We included all patients with a HIV diagnosis, no history of
antiretroviral therapy (ART) intake, attending one of the three clinics
(Kobler (K), 56 Dean Street (DS) and West London (WL)), between
2011 and 2013 who started antiretrovirals. Reverse transcriptase (RT)
and protease region sequencing was performed using Vircotype
virtual phenotype resistance analysis. Drug resistance mutations
were identified according to Stanford University HIV Drug Resistance
Database (http://hivdb.stanford.edu/).
Results: Among 1705 HIV-1-infected patients enrolled in the study,
1252 were males (919 were MSM), 107 were females and 346 had
no gender recorded. Ethnicity was 51.1% white British/Irish/other,
6.1% African, 2.1% Caribbean, 2.8% Asian, 1.3% Indian/Pakistani/
Bangladeshi, 4.2%, other, 3.2% not stated, and 29.2% unknown. 547
were from K (84.3% males, 48.3% MSM), 826 were from DS (84.3%
males, 71.9% MSM), and 109 from WL (87.2% males, 56.0% MSM),
223 from other sites not specified. 77.5% (1321 of 1705) of patients
had baseline viral resistance testing performed. Prevalence of
primary resistance in those with a baseline viral resistance test was
13.5% overall: 19.3% in K, 14.9% in DS, and 14.7% in WL. The most
common mutations detected were: NRTI: 184V, 215F, 41L; NNRTI
103N, 179D, 90I; PI 90M, 46I, and 82A. Among patients who tested
with TDR, 79.1% had one single mutation, 18.7% and 2.2% exhibited
dual or triple class-resistant viruses, respectively.
Conclusions: This study across a large HIV Medicine Directorate
reported an overall TDR prevalence which is higher than that
previously published and with significant rates of NNRTI resistance
at baseline.
References
1. Geretti AM, Booth C, Labbett WA, Murphy G, Johnson M. Antivir
Ther. 10, Suppl 1:S131 (abstract no. 118).
2. Payne BA, Nsutebu EF, Hunter ER, Olarinde O, Collini P, Dunbar JA,
et al. Low prevalence of transmitted antiretroviral drug resistance in
a large UK HIV-1 cohort. J Antimicrob Chemother. 2008;62(3):4648.
P216
Use of deep sequencing data for routine analysis of HIV
resistance in newly diagnosed patients
Jose-Angel Fernández-Caballero1; Natalia Chueca1; Marta Alvarez1;
Dimitri Gonzalez2 and Federico Garcı́a1
1
Microbiology & Infectious Diseases, HU San Cecilio, Granada, Spain.
2
Bioinformatics, ABL Spain, Barcelona, Spain.
157
Introduction: Use of deep sequencing is becoming a critical tool in
clinical virology, with an important impact in the HIV field for routine
diagnostic purposes. Here, we present the comparison of deep and
Sanger sequencing in newly diagnosed HIV patients, and the use of
DeepChek v1.3 & VisibleChek for their interpretation and integration
with virological and clinical data.
Patients and Methods: Plasma samples from 88 newly diagnosed
HIV-1-infected patients were included in the study. Median age (IQR)
was 37 (2747), median CD4 count (IQR) was 387 (220554), and
85% were males. Median Viral Load (Log, IQR) was 5.03 (4.515.53).
Deep sequencing was obtained using a GS-Junior (Roche). Sequences
were preprocessed with the 454 AVA software; aligned reads were
uploaded into the DeepChek v1.3 system (ABL SA). Sanger sequences
(Trugene), were uploaded in parallel. Stanford algorithm (version 7.0)
resistance interpretation to first line drugs and all the mutations
(score]5) were analyzed. For deep sequencing, 1%, 5% and 10%
thresholds were chosen for resistance interpretation.
Results: Using VisibleChek for analysis, we were able to describe the
detection of any mutation using Sanger in 37/88 patients, with a total
number of 50 Stanford ]5 mutations, K103N and E138A being the most
prevalent (n4). Using UDS-1%, we found 72/88 patients with at least
one mutation (total of 206 Stanford ]5 mutations). Using Sanger data,
9/88 patients (10.22%) showed any resistance to NNRTIs, while none
showed resistance to NRTIs or PIs. Using UDS-10% increased resistance to
NRTIs [3/88 (3.40%)], to NNRTIs 12/88 (13.63%), and to a lesser extent to
PIs [1/88 (1.13%)]. Using UDS-5% increased resistance to NRTIs [4/88
(4.54%)] and to NNRTIs [12/88 (13.63%)], but not to PIs. Using UDS-1%
increased resistance to all classes: NRTIs [14/88 (15.90%)], NNRTIs [26/88
(30.68%)], and PIs [6/88 (6.81].
Conclusions: DeepChek and VisibleChek allow for an easy, reliable
and rapid analysis of UDS data from HIV-1. Compared to Sanger data,
UDS detected a higher number of resistance mutations. UDS with a 5
&10% threshold resulted in an increase in the number of patients
with any degree of resistance mainly to NRTI, NNRTIs. Going down as
low as 1% increased resistance to all classes. A correct definition of
clinically relevant thresholds for the interpretation of minor variant
detection for different classes of ARVs is needed.
P217
New dolutegravir resistance pattern identified in a patient
failing antiretroviral therapy
Andreas Carganico1; Stefan Dupke1; Robert Ehret2; Thomas Berg2;
Axel Baumgarten1; Martin Obermeier2 and Hauke Walter2
1
Praxis, MIB Medical Infectiology Center Berlin, Berlin, Germany.
2
Laboratory Berg, MIB Medical Infectiology Center Berlin, Berlin,
Germany.
Introduction: The most recently approved antiretroviral, the integrase
inhibitor dolutegravir (DTG), is described to be a very potent drug with
a unique resistance profile, but a certain degree of cross-resistance to
RAL or EVG induced drug resistance, which is mediated mainly by
integrase mutations at positions 140 and 148. The impact of a single
N155H mutation to DTG resistance is described to be minor. However,
there is only rare data available about the impact of N155H in the
context of secondary site integrase mutations. Here, we present a case
of virological failure in a DTG treated patient based on N155H mutation
background.
Methods: Therapy monitoring of an HIV-HCV co-infected patient
harbouring already an omni-drug-class resistant HIV-1 in consequence of more than 20 years ART history. Drug susceptibility testing
was performed by RT-PCR from plasma and subsequent Sanger
sequencing. Tropism testing was done from proviral DNA with FPR
cut-offs according to the German recommendations.
Poster Abstracts
Results: In 2013, the patient harbouring a virus with high level
resistance to all RTI and PI received a regimen containing FTC, TDF,
DRV/r, RPV, T20, and RAL to handle a viral load of 5000 RNA copies/
mL, but never achieved fully suppressed viral load. In June 2013,
after S119R, N155H and E157Q mutations in viral integrase were
detected, the patient received DTG, and RAL was stopped. One
month later, when viral load was undetectable for the first time since
2007, ART was de-escalated by removing T20. Since February 2014,
low-level viral load was re-detectable. Two new mutations T97A and
S147G in the integrase and no other new resistance associated
mutations in protease and reverse transcriptase in comparison to the
sample analyzed in June 2013 were detected.
Conclusions: Highly resistant HIV-1 strains have been a common
problem in the past. Their frequencies were pushed back by highly
potent ART, but the virus is still able to become resistant against all
available antiretrovirals at once. The here documented strain became
resistant to DTG without carrying mutations at the described
positions 140 and 148, but in the context of integrase N155H. Since
N155H alone is described not to contribute sufficient resistance to
DTG, there seems to be a need to re-check viruses with N155H plus
minor mutations (like T97A, S119R, S147G and E157Q) potentially
contributing to DTG resistance.
P218
Transmitted antiretroviral drug resistance mutations in
newly diagnosed HIV-1 positive patients in Turkey
Murat Sayan1; Fatma Sargýn2; Dilara Inan3; Dilek Yýldýz Sevgi4;
Aysel Kocagül Celikbas5; Kadriye Yasar6; Figen Kaptan7; Selda Sayýn
Kutlu8; Nuriye Tasdelen Fýsgýn9; Ayse Inci10; Nurgül Ceran11;
Ýlkay Karaoðlan12; Atahan Cagatay13; Mustafa Kemal Celen14;
Suda Tekin Koruk15; Bahadýr Ceylan16; Taner Yýldýrmak17;
Halis Akalýn18; Volkan Korten19 and Ayse Willke20
1
Clinical Laboratory, Kocaeli University, Kocaeli, Turkey. 2Infectious
Diseases, Goztepe Hospital, Medeniyet University, Istanbul, Turkey.
3
Infectious Diseases, Akdeniz University, Antalya, Turkey. 4Infectious
Diseases, Sisli Etfal Hospital, Istanbul, Turkey. 5Infectious Diseases,
Ankara Numune Hospital, Ankara, Turkey. 6Infectious Diseases,
Bakýrköy Egitim Arastýrma Hospital, Istanbul, Turkey. 7Infectious
Diseases, Atatürk Hospital, Katip Celebi University, Izmir, Turkey.
8
Infectious Diseases, Pamukkale University, Denizli, Turkey.
9
Infectious Diseases, Mayis University, Samsun, Turkey. 10Infectious
Diseases, Istanbul Kanuni Hospital, Istanbul, Turkey. 11Infectious
Diseases, Haydarpasa Educational and Research Hospital, Istanbul,
Turkey. 12Infectious Diseases, Gaziantep University, Gaziantep,
Turkey. 13Infectious Diseases, Istanbul University, Istanbul, Turkey.
14
Infectious Diseases, Dicle University, Diyarbakir, Turkey. 15Infectious
Diseases, Harran University, Urfa, Turkey. 16Infectious Diseases,
Bezm-i Alem University, Istanbul, Turkey. 17Infectious Diseases,
Istanbul Okmeydani Hospital, Istanbul, Turkey. 18Infectious Diseases,
Uludag University, Bursa, Turkey. 19Infectious Diseases, Marmara
University, Istanbul, Turkey. 20Infectious Diseases, Kocaeli University,
Kocaeli, Turkey.
Introduction: The objective of this study was to determine the
transmitted drug resistance mutations (TDRMs) in newly diagnosed
HIV-1 positive patients in Turkey.
Material and Methods: The study was carried out between 2009 and
2014 and antiretroviral naı̈ve 774 HIV-1 infected patients from 19
Infectious Diseases and Clinical Microbiology Departments in Turkey
were included; gender: 664 (86%) male, median age: 37 (range;
177), median CD4T-cell: 360 (range; 11320) count/mm3,
median HIV-RNA load: 2.10E6 (range; 4.2E27.41E8) IU/mL.
HIV-1 drug resistance mutations were detected by population based
158
Poster Abstracts
sequencing of the reverse transcriptase (codon 41238) and
protease (codon 199) domains of pol gene of HIV-1, and analyzed
according to the criteria by the World Health Organization 2009 list
of surveillance drug resistance mutations [1].
Results: The patients had TDRMs to NRTIs (K65R, M184V), NNRTIs
(K101E, K103N/S, G190A/E/S, Y181I/C, Y188H/L) and PIs (M46L, I54V,
L76V, V82L/T, N83D, I84V, L90M). The prevalence of overall TDRMs
was 6.7% (52/774). Resistance mutations were found to be 0.7% (6/
774), 4.1% (32/774) and 2.1% (17/774) to NRTIs, NNRTIs and PIs drug
groups, respectively. Three patients had NRTIsNNRTs resistance
mutations (M184VK103N) as multi-class drug resistance. However, thymidine analogue resistance mutations (TAMs) determined
two distinct genotypic profiles in the HIV-1 reverse transcriptase:
TAM1: M41L, L210W and T215Y, and TAM2: D67N, K70R, K219E/Q,
and T215F. The prevalence of TAM1 and TAM2 were 7.7% (60/774)
and 4.3% (34/774), respectively.
Conclusions: The TDRMs prevalence of antiretroviral naı̈ve HIV-1
infected patients may be suggested current situation of Turkey. These
long-term and large-scale results show that the resistance testing
must be an integral part of the management of HIV infection in
Turkey.
Reference
1. Bennett DE, Camacho RJ, Otelea D, Kuritzkes DR, Fleury H,
Kiuchi M, et al. Drug resistance mutations for surveillance of
transmitted HIV-1 drug resistance: 2009 update. PLoS One. 2009;4:
e4724.
P219
Comparison of HIV-1 drug resistance profiles generated
from novel software applications for routine patient care
1
2
3
Dimitri Gonzalez ; Benjamin Digmann ; Matthieu Barralon ;
Ronan Boulme3; Chalom Sayada3 and Joseph Yao2
1
R&D, ABL TherapyEdge Spain SL, Barcelona, Spain. 2Mayo Clinic,
Virology, Rochester, USA. 3ABL SA, R&D, Luxembourg, Luxembourg.
Introduction: Clinical laboratories performing routine HIV-1 genotyping antiviral drug resistance (DR) testing need reliable and up-to-date
information systems to provide accurate and timely test results to
optimize antiretroviral treatment in HIV-1-infected patients.
Materials and Methods: Three software applications were used to
compare DR profiles generated from the analysis of HIV-1 protease
(PR) and reverse transcriptase (RT) gene sequences obtained by
Sanger sequencing assay in 100 selected clinical plasma samples
from March 2013 through May 2014. Interpretative results obtained
from the Trugene HIV-1 Genotyping assay (TG; Guidelines v17.0)
were compared with a newly FDA-registered data processing module
(DPM v1.0) and the research-use-only ViroScore-HIV (VS) software,
both of which use the latest versions of Stanford HIVdb (SD v7.0) and
geno2pheno (G2P v3.3) interpretive algorithms (IA). Differences
among the DR interpretive algorithms were compared according
to drug class (NRTI, NNRTI, PI) and each drug. HIV-1 tropism
and integrase inhibitor resistance were not evaluated (not available
in TG).
Results: Overall, only 17 of the 100 TG sequences obtained yielded
equivalent DR profiles among all 3 software applications for every IA
and for all drug classes. DPM and VS generated equivalent results
with 99.9% agreement. Excluding AZT, DDI, D4T and rilpivirine (not
available in G2P), ranges of agreement in DR profiles among the
three IA (using the DPM) are shown in Table 1.
Conclusions: Substantial discrepancies (B75% agreement) exist
among the three interpretive algorithms for ETR, while G2P differed
from TG and SD for resistance to TDF and TPV/r. Use of more than
Abstract P219Table 1. Minimal and maximal agreement observed between each interpretive algorithm combination per
drug class
Drug class
NRTI
NNRTI
PI
TG vs. SD
TG vs. G2P
SD vs G2P
79% (ABC)99%
62% (TDF)99%
61% (TDF)99%
(3TC)
(3TC)
(3TC)
64% (ETR)96%
57% (ETR)87%
57% (ETR)89%
(NVP)
(EFV)
(EFV)
78% (LPV/r)
47% (TPV/r)94%
41% (TPV/r)
96% (NFV)
(DRV/r, LPV/r)
87% (SQV/r)
one DR interpretive algorithm using well-validated software applications, such as DPM v1.0 and VS, would enable clinical laboratories to
provide clinically useful and accurate DR results for patient care
needs.
P220
Analysis of transmitted HIV-1 drug resistance using 454
ultra-deep-sequencing and the DeepChek†-HIV system
Ana Garcia-Diaz1; Adele McCormick1; Clare Booth1;
Dimitri Gonzalez2; Chalom Sayada3; Tanzina Haque1;
Margaret Johnson1 and Daniel Webster1
1
Virology, Royal Free London NHS Foundation Trust, London, UK.
2
R&D, ABL TherapyEdge Spain SL, Barcelona, Spain. 3R&D, ABL SA,
Luxembourg, Luxembourg.
Introduction: Next-generation sequencing (NGS) is capable of
detecting resistance-associated mutations (RAMs) present at frequencies of 1% or below. Several studies have found that baseline
low-frequency RAMs are associated with failure to first-line HAART.
One major limitation to the expansion of this technology in routine
diagnostics is the complexity and laboriousness integral to bioinformatics analysis. DeepChek (ABL, TherapyEdge) is a CE-marked
software that allows automated analysis and resistance interpretation of NGS data.
Objective: To evaluate the use of 454 ultra-deep-sequencing
(Roche† 454, Life Sciences; 454-UDS) and DeepChek for routine
baseline resistance testing in a clinical diagnostic laboratory.
Methods: 107 newly diagnosed HIV-1-infected patients (subtypes: A,
n9; B, n 52; C, n21; D, n 2; F, n3; G, n1; CRF01, n7;
CRF02, n7; CRF06, n1; CRF07, n1; CRF10, n1 and unassigned complex, n2) with a median plasma viral load of 88,727
copies/mL (range: 13802,143,543) were tested by 454-UDS and
Sanger sequencing for the detection of protease and reverse
transcriptase RAMs. In addition, integrase RAMs were investigated
in 57 of them. Sequence analysis and resistance interpretation were
performed using DeepChek applying 1% and 20% thresholds for
variant detections; filters applied were comparison between Sanger
and 454-UDS, and Stanford and IAS list for resistance interpretation.
Results: The time elapsed from generation of raw 454 data (between
2,0005,000 sequences/sample) to elaboration of a resistance
report was approximately 10 minutes per sample, equivalent to
the time required for the same process using Sanger sequencing.
Four patients (3.7%) showed baseline resistance by Sanger and 454UDS at frequencies above 20%, which affected both NRTIs (n2) and
NNRTIs (n2). In addition, 12 patients (11.2%) showed transmitted
drug resistance (TDR) by 454-UDS at frequencies below 20% affecting
NRTIs (n 9), NNRTIs (n 7) and PIs (n2). Integrase resistance
was not detected at baseline by 454-UDS or Sanger sequencing.
159
Conclusions: DeepChek allowed easy and rapid analysis and interpretation of NGS data, thus facilitating the incorporation of this
technology in routine diagnostics. The use of NGS considerably
increased the detection rates of TDR to NRTI, NNRTIs and PIs. No
transmitted resistance to integrase inhibitors was found in our
population by Sanger sequencing or UDS.
P221
Time trends in HIV-1 transmitted drug resistance mutation
frequency in Poland
Milosz Parczewski1; Magdalena Witak-Jedra1;
Katarzyna Maciejewska1; Monika Bociaga-Jasik2; Pawel Skwara2;
Aleksander Garlicki2; Anna Grzeszczuk3; Magdalena Rogalska3;
Maria Jankowska4; Malgorzata Lemanska4; Maria Hlebowicz4;
Grazyna Baralkiewicz5; Iwona Mozer-Lisewska6; Renata Mazurek7;
Wladyslaw Lojewski7; Edyta Grabczewska8; Anita Olczak8;
Elzbieta Jablonowska9; Weronika Rymer10; Aleksandra Szymczak10;
Bartosz Szetela10; Jacek Gasiorowski10; Brygida Knysz10;
Anna Urbanska1 and Magdalena Leszczyszyn-Pynka1
1
Department of Infectious, Tropical Diseases, Pomeranian Medical
University in Szczecin, Szczecin, Poland. 2Department of Infectious
Diseases, Jagiellonian University Medical College, Kraków, Poland.
3
Department of Infectious Diseases and Hepatology, Medical
University of Bialystok, Bialystok, Poland. 4Department of Infectious
Diseases, Medical University of Gdañsk, Gdañsk, Poland.
5
Department of Infectious Diseases, J. Strus Hospital, Poznañ, Poland.
6
Department of Infectious Diseases, Poznan University of Medical
Sciences, Poznan, Poland. 7Department of Infectious Diseases,
Regional Hospital in Zielona Gora, Zielona Gora, Poland. 8Department
of Infectious Diseases and Hepatology, Nicolaus Copernicus
University Collegium Medicum, Bydgoszcz, Poland. 9Department of
Infectious Diseases and Hepatology, Medical University of Lódz, Lódz,
Poland. 10Department of Infectious Diseases, Hepatology, Wroclaw
Medical University, Wroclaw, Poland.
Introduction: In Poland, the HIV epidemic has shifted recently from
being predominantly related to injection drug use (IDU) to being
driven by transmissions among men-who-have-sex-with-men (MSM).
The number of new HIV cases has increased in the recent years,
while no current data on the transmitted drug resistance associated
mutations (tDRM) frequency trend over time are available from
2010. In this study, we analyze the temporal trends in the spread of
tDRM from 2008 to 2013.
Materials and Methods: Partial pol sequences from 833 antiretroviral treatment-naive individuals of European descent (Polish origin)
linked to care in 9 of 17 Polish HIV treatment centres were analyzed.
Drug resistance interpretation was performed according to WHO
Poster Abstracts
surveillance recommendations, subtyping with REGA genotyping
2.0 tool. Time trends were examined for the frequency of t-DRM
across subtypes and transmission groups using logistic regression
(R statistical platform, v. 3.1.0).
Results: Frequency of tDRM proved stable over time, with mutation
frequency change from 11.3% in 2008 to 8.3% in 2013 [OR: 0.91
(95% CI 0.801,05), p0.202] (Figure 1a). Also, no significant
differences over time were noted for the subtype B (decrease from
8.4% 2008 to 6.2% in 2013 [OR: 0.94 (95% CI 0.791.11), p0.45]
and across non-B variants [change from 22.6% 2008 to 23.1% in
2013, OR: 0.94 (95% CI 0.751.19), p0.62]. When patient groups
were stratified according to transmission route, in MSM there was a
trend for a NNRTI t-DRM decrease (from 6.8% 2008 to 1% in 2013,
OR: 0.61 (95% CI 0.341.02), p0.0655, slope 0.74%/year)
(Figure 1b), related to the subtype B infected MSM (decrease from
7% 2008 to 1% in 2013, OR: 0.61 (95% CI 0.341.03), p0.0662,
slope 0.75%/year). Overall tDRM frequency decrease was also
noted for the heterosexually infected patients [from 17.6% 2008 to
10.3% in 2013, OR: 0.83 (95% CI 0.671.02, p0.077, slope
2.041%/year)] but did not associate with drug class (Figure 1c).
In IDUs, the trends in t-DRM frequency were not significant over
time (change from 1.9% in 2008 to 0 in 2013 [OR:1.24 (95% CI 0.73
2.26), p0.4)].
Conclusions: The frequency of t-DRM in Poland is generally stable
over time. Decrease in the overall tDRM frequency in heterosexual
infected cases and NNRTI resistance in subtype B infected MSM may
be related to the higher treatment efficacy of current cART.
P222
High frequency of antiviral drug resistance and non-b
subtypes in HIV-1 patients failing antiviral therapy
in Cuba
Vivian Kouri1; Yoan Alemán1; Lissette Pérez1; Jorge Pérez2;
Carlos Fonseca3; Consuelo Correa1; Carlos Aragonés4; Jorge Campos4;
Delmis Álvarez4; Yoeri Schrooten5; Lore Vinken5; Celia Limia1;
Yudira Soto1; Anne-Mieke Vandamme6 and Kristel Van Laethem5
1
Virology Department, Laboratory of Sexually Transmitted Diseases,
Institute of Tropical Medicine ‘‘Pedro Kourı́’’, Havana, Cuba. 2Institute
of Tropical Medicine ‘‘Pedro Kourı́’’, Havana, Cuba. 3Institute of
Tropical Medicine ‘‘Pedro Kourı́’’, Hospital Division, Havana, Cuba.
4
Computer Department, Institute of Tropical Medicine ‘‘Pedro Kourı́’’,
Havana, Cuba. 5Department of Microbiology and Immunology,
Laboratory for Clinical and Epidemiological Virology, Rega Institute
for Medical Research, KU Leuven, Leuven, Belgium. 6Department of
Microbiology and Immunology, Laboratory for Clinical and
Epidemiological Virology, Rega Institute for Medical Research and
Centro de Malária e Outras Doenças, Leuven, Belgium.
Abstract P221–Figure 1. Trends in tDRM prevalence over time. (a) trends for the entire study group, (b) trends for MSM infected patients,
(c) trends in for heterosexual transmissions.
160
Poster Abstracts
regimen with extensive resistance. Genotypic analysis was performed
using population sequencing and 454 ultradeep sequencing of
integrase at time of raltegravir exposure.
Results: Both patients were diagnosed in early 1990s and received
mono- and dual therapy, followed by several cART-regimens. Due to
presence of extensive resistance, the genotypic susceptibility score of
these regimens never reached a score 2 and never resulted in
sustained virological suppression despite good adherence. Early
2012, the clinical condition of patient 1 worsened during persistent
failure of a mega-cART regimen despite excellent drug levels. Six
major PI, six minor PI, seven NRTI, six NNRTI and two INI mutations
plus DM-virus were detected (Table 1). Ultra-deep sequencing of
integrase showed the selection of Q148R, E138KQ148K, and
N155H variants and phenotypic raltegravir resistance was demonstrated. After addition of dolutegravir and enfuvirtide to the failing
regimen (zidovudine, lamivudine, tenofovir, etravirine, darunavir/
ritonavir, maraviroc), viral load (VL) decreased from 244,000 to B20
cps/mL within five months, CD4-count increased (33 to 272 mm3)
and the clinical condition improved substantially. In patient 2, similar
worsening of the clinical condition was observed late 2012 during
persistent failure on mega-cART. Five major PI, six minor PI, nine NRTI,
seven NNRTI and one INI mutation plus DM-virus were detected.
Ultra-deep sequencing showed selection of N155H, followed by Q95K
and V151I variants and phenotypic raltegravir resistance was demonstrated. Dolutegravir was added to his failing regimen (zidovudine,
lamivudine, etravirine, atazanavir/ritonavir, maraviroc) at a VL of
39,000 cps/mL. Sustained virological suppression was reached within
five months with considerable increase of CD4-count (41 to 175 mm3)
and slight improvement of clinical condition.
Conclusions: We present the first patients with extensive integrase
resistance who were treated with dolutegravir in clinical practice and
who achieved excellent virological and immunological success. These
cases demonstrate the high genetic barrier of dolutegravir.
Introduction: Emergence of HIV-1 drug resistance may limit the
sustained benefits of antiretroviral therapy (ART) in settings with
limited laboratory monitoring and drug options. The objective is to
implement the surveillance of drug resistance and subtypes in HIV-1
patients failing ART in Cuba.
Methods: This study compiled clinical and genotypic drug resistance
data 588 ART-experienced HIV-1 patients attending a clinical center
in Havana in 20092013. Drug resistance testing was performed as
part of routine clinical care. Drug resistance mutations and levels
were determined using Rega version 8.0.2.
Results: Eighty-three percent received solely ART containing at least
three drugs. Patients from 2009 to 2010 were longer treated
(median: 4.9 vs 2.7 years) and exposed to more ART regimens
(median: 4 vs 2 regimens) compared to patients from 20112013.
Nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside RTI
(NNRTI) and PI mutations were present in 83.5, 77.4 and 52.0%. Fullclass resistance (FCR) to NRTI, NNRTI, PI and multidrug resistance
(MDR) were detected in 25.0, 33.7, 11.4 and 6.3%. FCR to NRTI,
NNRTI, PI and MDR were present in 12.8, 28.7, 0 and 0% after firstline failure (164 patients) and in 23.1, 34.6, 3.8 and 3.1% after
second-line failure (130 patients). Subtype B (32.5%), BG recombinants (19.6%) and CRF19_cpx (16.2%) were the most prevalent
genetic forms. Subtype distribution did not change significantly
between 20092010 and 20112013, except for BG recombinants
that increased from 12.2 to 21.3% (p 0.002).
Conclusions: Our study found a high prevalence of drug resistance
and supports the need for appropriate laboratory monitoring in
clinical practice and access to drug options in case of virological
failure.
P223
Use of dolutegravir in two INI-experienced patients with
multiclass resistance resulted in excellent virological and
immunological responses
P224
Laura Marije Hofstra1; Monique Nijhuis1; Tania Mudrikova2;
Axel Fun1; Pauline Schipper1; Margriet Schneider2 and
Annemarie Wensing1
1
Medical Microbiology, University Medical Center Utrecht, Utrecht,
Netherlands. 2Infectious Diseases and Internal Medicine, University
Medical Center Utrecht, Utrecht, Netherlands.
Introduction: Dolutegravir is a second generation integrase inhibitor
with a proposed high genetic barrier to resistance. However, in
clinical trials, decreased virological response was seen in a subset of
patients with prior exposure to raltegravir and multiple integrase
resistance mutations.
Methods: We describe two cases of HIV subtype B-infected patients
starting dolutegravir after previous failure on a raltegravir-containing
Resistance remains a problem in treatment failure
Martin Obermeier1; Robert Ehret1; Andreas Wienbreyer2;
Hauke Walter1; Thomas Berg1 and Axel Baumgarten3
1
Laboratory, Medical Center for Infectious Diseases, Berlin, Germany.
2
Clinical Research, Medical Center for Infectious Diseases, Berlin,
Germany. 3Outpatients Clinic, Medical Center for Infectious Diseases,
Berlin, Germany.
Introduction: Proven resistance against HIV drugs, either by phenotyping or genotyping is a rare event in clinical trials. The overall
assumption of drug resistance disappearing is additionally driven
by the recommendations to screen for transmitted drug resistance, leading to large numbers of examinations with relatively low
Abstract P223Table 1. Cumulative result of the performed genotypic analyses of patients 1 and 2 before start of dolutegravir and
their interpretation by Stanford HIVDB v7.0
RT
Pt. 1
M41L, D67N, T69i, L74V, M184V, L210W, T215Y, A98G,
PR
IN
M46L, I50V, I54V, V82A, I84V, L90M
Q148R, E138K
M46I, I54V, V82C, I84V, L90M
N155H
K103N, V108I, E138G, Y181C, G190A
Pt. 2
M41L, D67d, T69G, K70R, L74I, M184V, L210W, T215Y,
K219E, A98G, L100I, K103N, V106I, V108I, E138K, G190A
3TC ABC AZT D4T DDI FTC TDF EFV ETR NVP RPV ATV DRV FPV IDV LPV NFV SQV TPV DTG EVG RAL
Pt. 1
Pt. 1
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
I
R
R
R
R
R
R
I
I
R
R
R
R
R
R
R
R
R
R
R
R
I
S
R
R
R
R
161
rates of resistance. Goal of our analysis was to assess if drug
resistance in treatment failure is also decreasing outside of clinical
trials.
Materials and Methods: The MIB database at timepoint of analysis
consists of data from 2876 HIV infected patients. Besides various
laboratory parameters, clinical data and treatment history is
included. HIV-1 protease and reverse transcriptase sequences were
analyzed using the HIV-GRADE drug resistance algorithm. As in only a
small number of patients genotypic resistance testing for integrase
inhibitors was performed, mainly due to reimbursement reasons, it
was assumed that failing treatment on a previous integrase inhibitor
containing regimen is equate to resistance.
Results: Of the 2876 patients in the database, 220 had a treatment
change due to treatment failure between 2009 and 2012, a
genotypic resistance testing at an appropriate timepoint of maximum
four weeks before treatment change and a treatment duration of at
least six months before treatment failure. In 2009, 61% of patients
showed no drug resistance while 39% showed resistance against one
or more drug classes (two or more drug classes: 19.5%; three or
more drug classes: 2.4%, four drug classes 2.4%). In 2012, no
resistance was found in 52% of patients while resistance against
three or more drug classes was found in nearly 14% of patients (one
or more: 48%; two or more 23%; four classes: 4.5%).
Conclusions: Treatment failure with viral load sufficiently high for
drug resistance testing was not frequently observed in our database.
Nevertheless, treatment failure was often associated with drug
resistance against at least one drug class. With more use of the
newer drug classes, resistance against those new classes will become
more common and rates of multiclass resistance will be increasing.
P225
Time to virologic failure for patients taking their first
antiretroviral regimen and the subsequent resistance
profiles
Frederic Crouzat1; Anita Benoit2; Colin Kovacs1; Graham Smith1;
Nathan Taback3; Ina Sandler4; Jason Brunetta1; Benny Chang1;
Barry Merkley1; David Tilley1; David Fletcher1; Dipen Kalaria5 and
Mona Loutfy1
1
Infectious Diseases, Maple Leaf Medical Clinic, Toronto, Canada.
2
Women’s College Research Institute, Women’s College Hospital,
Toronto, Canada. 3Department of Statistical Sciences, University of
Toronto, Toronto, Canada. 4Data Management, Maple Leaf Medical
Clinic, Toronto, Canada. 5Virology and Vaccines, Janssen Inc., Toronto,
Canada.
Introduction: The resistance profiles of first-line antiretroviral
therapy (ART) regimens after virologic failure have yet to be studied
in a clinic setting in the modern treatment era. Time to virologic
failure among three standard first-line regimens and the resistance
profiles of these failures were compared.
Materials and Methods: All HIV-positive persons aged 16 and over
starting a three-drug first-line ART regimen were retrospectively
identified at a Toronto community clinic (1 January 20061 January
2013). The regimens included a backbone of two NRTIs and a third
agent; a PI, an NNRTI, or an II. Patients must have been on treatment
for at least 14 days and have at least one VL test within 6 months
after starting treatment. The primary outcome was virologic failure
defined as either: no suppression by 6 months, or after suppression,
two consecutive, detectable VL200 copies/mL at least 14 days apart
or one VL 200 copies/mL. Time to failure was compared using
a proportional hazards model adjusting for demographic and clinical
factors. Resistance profiles of NRTIs and third agents are described in
patients with virologic failure who had both baseline and virologic
failure genotypes.
Poster Abstracts
Results: Six hundred sixty patients (93% male) were included with a
mean age of 38.9 and a median follow-up period of 35.3 (32.239.3)
months. Distribution of third agent use was: PI 37.3% (n246),
NNRTI 55.9% (n 369) and II 6.8% (n 45). Virologic failures
occurred in 81/246 (33%) with PI, 87/369 (24%) with NNRTI and
11/45 (24%) with II. Compare to PIs, time to failure was longer with
NNRTIs (p 0.0013) and similar for IIs (p 0.1562). No evidence that
failure with NNRTIs was different from IIs (p 0.9139). Of the 660
patients, 567 (86%) had a baseline genotype. Of the 567 patients,
179 had virological failure. Of the 179, 145(81%) had a baseline
genotype and only 37 (21%) had both a baseline and follow-up
genotype. Upon failure, emerging ART resistance was rare. No new PI
or II mutations were identified and one new NNRTI (Y181C) mutation
was identified. Three patients taking PI-based regimens developed
NRTI mutations (M184V, M184I, T215Y).
Conclusions: Time to virologic failure was significantly greater in the
NNRTI group compared to the PI group. If failure did occur, ART
resistance rarely developed with no PI mutations but a few NRTI
mutations in those taking PI-based regimens, and NNRTI mutations
in those taking NNRTI-based regimen.
P226
Seroincidence of HIV and prevalence of transmitted drug
resistance of HIV-1 strains among persons seeking voluntary
counselling and testing in Taiwan
Wen-Chun Liu1; Lan-Hsin Chang1; Pei-Ying Wu2; Yu-Zhen Luo2;
Cheng-Hsin Wu1; Yi-Ching Su1; Chung-Chi Lai3; Sui-Yuan Chang4 and
Chien-Ching Hung1
1
Internal Medicine, National Taiwan University Hospital, Taipei City,
Taiwan. 2Center for Infection Control, National Taiwan University
Hospital, Taipei City, Taiwan. 3Internal Medicine, Kaohsiung Medical
University Hospital, Kaohsiung City, Taiwan. 4Clinical Laboratory
Sciences and Medical Biotechno, National Taiwan University College
of Medicine, Taipei City, Taiwan.
Introduction: The total case number of persons who are newly
diagnosed with HIV continues to increase in Taiwan and men who
have sex with men (MSM) have re-emerged as the leading risk group
for HIV transmission. In this study, we aimed to estimate the
incidence rate of HIV infection among those individuals who sought
voluntary counselling and testing (VCT) service at a university
hospital.
Methods: Between 1 April, 2006 and 31 December, 2013, 18,246
tests for HIV antibody were performed among 12143 individuals at
the VCT service. A total of 2157 individuals who tested negative for
anti-HIV antibody had subsequent follow-up tests at the same VCT
service, which composed the study population for estimation of
incidence rate of recent HIV infection. The BED assays were used to
identify recent HIV infections that occurred within the previous six
months before seeking VCT service.
Results: During the 6.5-year study period, 647 individuals were
diagnosed as being HIV-positive, with an overall HIV seroprevalence
of 3.55% (95% CI 3.273.82). The overall incidence rate of HIV
infection was estimated 4.13 per 100 person-years of follow-up (95%
CI 3.674.69 per 100 person-years of follow-up). MSM had an
estimated 10-fold higher seroprevalence and seroincidence of HIV
than heterosexuals. Of 647 clients testing positive for HIV, 603 clients
were MSM (93.2%) and 477 patients (70.8%) subsequently sought
HIV care at the hospital; 226 (47.4%) were diagnosed as having
recent HIV infections by the BED assay, while 244 (51.2%) long-term
infection and 7 without data by the BED assay. Of those patients,
173 (75.6%) and 178 patients (73.0%) with recent HIV infection and
162
long-term infection had data of transmitted drug resistance mutations, respectively. The prevalence of transmitted drug resistance
mutations to any class of antiretroviral therapy was 9.0% and 10.6%
(p 0.68), respectively, of the HIV-1 strains from the patients with
recent HIV infection and long-term infection, respectively.
Conclusions: The seroincidence rate of HIV among persons seeking
VCT was estimated 4.13 per 100 person-years of follow-up. The
prevalence of transmitted drug resistance to any class of antiretroviral agents was similar between those who were recently
infected with HIV and those who had long-term infection in Taiwan.
P227
Early clinical response and presence of viral resistant
minority variants: a proof of concept study
Annapaola Callegaro1; Elisa Di Filippo2; Noemi Astuti2; Paula Andrea
Serna Ortega1; Marco Rizzi2; Claudio Farina1; Daniela Valenti2 and
Franco Maggiolo2
1
Microbiology and Virology, AO Papa Giovanni XXIII, Bergamo, Italy.
2
USC Infectious Diseases, AO Papa Giovanni XXIII, Bergamo, Italy.
Introduction: Traditional genotyping assays detect viral variants
present in at least 1525% of the entire virus population. We tested
the Next generation GS Junior System (NGS) setted with a detection
limit of 0.05% and evaluated the clinical relevance of low prevalent
mutations.
Methods: NGS was performed on the plasma of 26 infected individuals who started a TDF/FTC/RPV (15 subjects) or TDF/FTC/EFV (11
subjects) cART after a routine HIV-1 drug-resistance negative test by
Viroseq HIV-1 Genotyping System. Amplicon Sequencing of HIV-1 RT
and PR Plate (Roche) was performed following the manufacturer’s
instructions. HIV-1 variants were analyzed by a specific HIV-1 tool
by AVA software v. 2.7. The updated IAS resistance mutations list
(March 2013) was considered for the analysis of resistance positions. Patients were followed testing viral load and immunologic
parameters.
Results: Twenty four males and two females with a mean age of 43
years were included. Twenty-one were nave for cART. At baseline,
median HIV-RNA was 4.57 log copies/mL (range 2.156.57) and CD4
count 315 cells/mcL (range 16648). In 18 patients, NGS did not
detect any additional variant relevant for the selected cART compared
to population genotyping. In the remaining eight patients resistance
conferring mutations to part of the ongoing regimen were detected.
Single mutations E138K (two cases) and M184V in three distinct
patients and V90IG190E; M184VA98S; Y215FV118IT215I;
L210ST215IF227L; and A62VD67GK70N188H in the remaining five subjects. In all cases, the mutation prevalence was
inferior to 5%. The mean daily reduction of VL was 3759 copies/mL
in patients without NGS detected mutations and 1045 copies/mL in
those with mutations. The median KM estimates for reaching an HIVRNA blood level B50 copies/mL were 127 days and 161 days, respectively. One patient without baseline resistance selected for M184I
E138KT215I (NGS) after four months of TDF/FTC/RPV therapy.
Conclusions: NGS detected low-frequency HIV-1 variants harbouring
RT drug resistance mutations that could have affected the therapy
outcome. However, viral decay in an early cART phase was not
affected by the presence of resistant minority variants. The low
prevalence of the detected mutation, the limited effect on the
combination regimen and the potency of cART components could be
possible explanations of our findings. Longer follow-up and larger
casuistries are needed to determine the clinical relevance of NGS in
routine clinical practice and eventually define a clinically relevant
mutations’ prevalence.
Poster Abstracts
P228
Resistance mutations in protease gene at baseline are not
related to virological failure in patients treated with
darunavir/ritonavir monotherapy
Angela Gutierrez-Liarte; Ana Gomez-Berrocal; Carmen Saez;
Jorge Valencia; Ignacio Santos and Jesus Sanz
Infectious Diseases, Hospital de La Princesa, Madrid, Spain.
Introduction: Monotherapy with darunavir plus ritonavir (DRV/r) is a
good maintenance strategy for suppressed HIV-infected patients. The
clinical trials designed to prove the efficacy of PI/r do not include
patients with resistance mutation in protease gene [1,2]. Sometimes
in routine practice, basically to avoid NRTIs toxicity, monotherapy
with DRV/r is used despite PI resistance mutations. The aim of this
study is to know the effect of previous protease resistance mutation
on DRV/r monotherapy efficacy.
Material and Methods: We designed an observational cohort study of
adults in treatment with DRV/r monotherapy in a tertiary Spanish hospital
since 2011 to 2014. Demographic data and clinical outcomes were
described. The analysis of efficacy was done according to the snapshot
algorithm (defining virological failure as viral load 50 copies/mL, ITTe, at
48 and 96 weeks). We analyzed the difference of efficacy between
patients with and without baseline resistance mutations at 48 and 96
weeks by using the x2 test; and during the follow-up by using the Kaplan
Meier test. The statistical analysis was done with SPSS 17.0.
Results: Eighty-nine patients were included in the cohort but 14 were
excluded because they had not reached more than six months with
monotherapy. The cohort was composed mainly by men (78%), the
medium age was 51 years (SD910), 35% were MSM and 19% were
former IDU. Twenty-four patients (35%) had a previous diagnosis of AIDS.
The mean time taking NRTIs was 10.5 years (SD95.4). Sixty-four patients
(85%) had been treated with PI in the past. Previous failure with PI had
been reported in 15 (20%). A resistance mutation test had been done at
baseline in 45 patients (51%). Twenty-two patients (29%) had some
mutations in protease gene, 10 patients (13%) had major mutations and
1 patient had some mutations of resistance for darunavir (I64V). At 48
weeks, 93% (CI 95% 8698%) had VLB50 copies/mL, and 79% (CI 95%
6789%) at 96 weeks. There were not differences between patients with
or without resistance mutations (p0.53). After a median follow-up of
70 weeks, 88% of patients remain free of virological failure and there were
not differences between both groups.
Conclusions: According to these data, previous resistance mutations
in the protease gene, which do not affect darunavir, are not related
with the efficacy in patients treated with DRV/r monotherapy.
References
1. Arribas JR, Horban A, Gerstoft J, Fätkenheuer G, Nelson M,
Clumeck N, et al. The MONET trial: darunavir/ritonavir with or
without nucleoside analogues, for patients with HIV RNA below 50
copies/ml. AIDS. 2010;24(2):22330.
2. Valantin MA, Lambert-Niclot S, Flandre P, Morand-Joubert L, Cabié
A, Meynard JL, et al. Long-term efficacy of darunavir/ritonavir monotherapy in patients with HIV-1 viral suppression: week 96 results from the
MONOI ANRS 136 study. J Antimicrob Chemother. 2012;67(3):6915.
P229
Primary drug resistance at diagnosis of HIV-1 infection: a
Portuguese cohort
Nuno Rocha Pereira; Raquel Duro; Carmela Piñero;
Cristóvão Figueiredo; Ana Soa Santos; Jorge Soares; Rosário Serrão
and António Sarmento
Infectious Diseases, Centro Hospitalar São João, Porto,
Portugal.
163
Poster Abstracts
Abstract P229–Table 1. General characteristics of the patients.
Abbreviations used in the table: SD - Standard deviation; MSM Men that have sex with men; CD4 - CD4 T cell lymphocytes
Characteristics
n624
Sex:
Male
447 (71.6%)
Female
177 (28.4%)
Age (mean9SD)
40.92913.38
in the distribution of the parameters age, sex, CD4-cell count,
and viral load, between groups with and without resistance was
identified. Resistance-associated mutations were significantly more
common in patients with non-B HIV-1 subtypes (15.4% vs 9.8%;
p0.048) and in those presenting with AIDS (18.2% vs 11.1%;
p0.03).
Conclusions: Prevalence of resistance-associated mutations identified in this study was similar to those reported in similar studies from
Western Europe. Knowledge about the epidemiology of primary
resistance in our country is important in order to improve HIV
care.
Risk for HIV acquisition
Heterosexual
436 (70.1%)
MSM
138 (22.2%)
Injecting drug user
Others
CD4-cell count /mL (mean9SD)
HIV-1 viral load copies/mL (mean9SD)
46 (7.4%)
2 (0.3%)
TREATMENT OF ADOLESCENTS AND
CHILDREN
3219254
70572591928167
Introduction: Presence of viral mutations conferring resistance to
antiretroviral drugs has potential impact on success of antiretroviral
therapy (ART). The aim of this study was to describe the prevalence
of resistance-associated mutations in HIV-infected patients without
prior ART in a Portuguese cohort.
Materials and Methods: Retrospective single-centre study of
patients newly diagnosed with HIV-1 infection between 2006 and
2012. Resistance genotyping was obtained with HIV TRUGENE†
and Viroseq† tests and the analysis of drug resistance was based
on the Stanford University HIV Drug Resistance Database. Epidemiological data was also gathered. Continuous variables were summarized by mean and standard deviation, whereas categorical variables
were presented as proportions. Comparison of proportions was
performed with Chi square and Fisher exact test while means
were compared with Student test. Statistical significance was
assumed when p B0.05. Statistical analysis was performed with
SPSS 21.0† .
Results: Resistance testing was performed in 624 patients. General
characteristics of the patients are summarized in Table 1. Mutations
were found in 291 (46.6%) patients but resistance-associated mutations were present in 79 (12.7%) patients. Resistances to different
drug classes were the following: NNRTIs-resistance in 42 (6.7%)
patients; NRTIs-resistance in 19 (3.0%) patients; PIs-resistance in
30 (4.8%) patients. Only 10 (1.6%) patients presented simultaneous resistance-associated mutations to more than one class of
drugs. There were no statistical significant differences between the
years at which HIV-1 was diagnosed. Also no significant difference
P231
Lamivudine monotherapy as a safe option for HIV-infected
paediatric clients with adherence challenges: new evidence
from a large South African cohort
Verena Linder1; Cheree Goldswain1; Gerald Boon1; Craig Carty2;
Valerie Jackson3; Kim Harper1 and John Lambert4
1
Health, Paediatrics, Eastern Cape, East London, South Africa. 2Social
and Clinical Research, The Relevance Network, Johannesburg, South
Africa. 3Clinical Audits and Surveillance, The Rotunda Hospital,
Dublin, Ireland. 4Infectious Diseases, Mater Misericordiae University
Hospital, Dublin, Ireland.
Introduction: HIV-infected children in resource-poor settings comprise a unique population who require antiretroviral therapy (ART)
in careful consideration of social and structural barriers to compliance. Given these aggregate challenges and emerging research
into ‘‘holding’’ treatment options, we investigated the efficacy of
lamivudine monotherapy (LM) as an alternative to more complex
second and third line therapies.
Methods: A retrospective review of all eligible LM events (6
months) from a cohort of two linked health facilities in the Eastern
Cape Province, South Africa was undertaken. Events were disaggregated according to absolute CD4 count at initiation (Group 1: 200
cells/L, n64; Group 2: 200cells/L, n10). Study endpoints were
defined as a decline of absolute CD4 200 cells/L (Group 1), WHO
stage 3 or 4 event (Groups 1& 2), or initiation of second or third line
(Groups 1 & 2).
Abstract P231Table 1. Characteristics for LM-initiated patients
All LM Events
(n 74)
Male (n, %)
Group 1: Baseline
Group 2: Baseline
CD4 200 cell/mL (n 64) CD4 200 cells/mL (n10)
p
43 (58)
38 (59)
5 (50)
0.576
Age at LM initiation, years (median, IQR)
9.7 (6.511.8)
9.0 (6.411.2)
11.9 (1014.4)
0.010
Duration of LM, months (median, IQR)
11.5 (7.117.4)
12.9 (7.417.9)
7.1 (5.19.1)
0.126
Final CD4, cells/mL (IQR, final prior to switch or last on LM) 429 (212593)
471 (325632)
29 (1659)
0.0001
0.185
Patients with overall decrease in CD4 (n, %)
64 (86.5)
58 (90.6)
6 (60)
Patients with 25% decrease in CD4 (n, %)
50 (67.6)
44 (68.8)
6 (60)
0.325
17 (23)
6 (8.1)
11 (17.2)
5 (7.8)
6 (60)
1 (10)
0.003
0.814
Patients switched to second or third line therapy (n, %)
Stage 3 or 4 event (n, %)
164
Results: Seventy-four eligible LM events were identified among 71
HIV-positive children (58% male; median age at LM 9.7 years and
median LM duration 11.5 months). CD4 decreases and measured
WHO stage 3 or 4 events did not yield overall significance between
groups (Table 1). No deaths were recorded.
Conclusions: LM offers a promising alternative approach to ART
management in young patients with an absolute CD4 200 cells/L
pending availability and/or willingness to adhere to second or third
line therapies. In more immunocompromised children, LM may be
considered as a last option if either the child or caretaker has
concerns about second or third line management, or has defaulted
repeatedly.
Poster Abstracts
References
1. Sohn AH, Hazra R. The changing epidemiology of the global
paediatric HIV epidemic: keeping track of perinatally HIV-infected
adolescents. J Int AIDS Soc. 2013;16:18555.
2. Van der Linden D, Lapointe N, Kakkar F, Ransy DG, Motorina A,
Maurice F, et al. The young and the resistant: HIV-infected adolescents at the time of transfer to adult care. J Ped Infect Dis. 2012. doi:
10.1093/jpids/pis106 First published online: December 19, 2012.
3. Miller D, El-Kholi R, Faragon JJ, Lodise TP. Prevalence and risk
factors for clinically significant drug interactions with antiretroviral
therapy. Pharmacotherapy. 2007;27:137986.
4. Liverpool HIV Drug Interactions website [Internet]. [cited 2004
Jul 3]. Available from: http://www.hiv-druginteractions.org.
P232
Potential drugdrug interactions in HIV-perinatally infected
adolescents on antiretroviral therapy in Buenos Aires,
Argentina
Ezequiel Cordova; Diego Cecchini and Claudia Rodriguez
Infectious Diseases Unit, Hospital Cosme Argerich, Buenos Aires,
Argentina.
TREATMENT STRATEGIES NAÏVE
PATIENTS
P233
Introduction: An increasing number of treatment-experienced
perinatally HIV-infected adolescents (PHA) are being transitioned
from paediatric centres to adult HIV-care [1]. Most of them had been
heavily exposed to antiretroviral drugs (ARVs), harbour drug-resistant
viruses and require non-antiretroviral medication due to comorbidities [2]. This may predispose for clinically significant drugdrug
interactions (CSDDIs) [3]. There are no studies concerning CSDDIs in
PHA. We aimed to evaluate the prevalence of concomitant medications and CSDDIs in PHA who were transitioned for adult HIV-care to
the Infectious Diseases Unit, Cosme Argerich Hospital, Buenos Aires
City, Argentina.
Material and Methods: Descriptive pilot cross-sectional study
(March to June 2014). PHA under ARVs at the time of the study
were assessed for concomitant medication. CSDDIs were screened
and categorized using the University of Liverpool Drug Interactions
Program (www.hiv-druginteractions.org) [4].
Results: Forty-five patients were included. Female sex: 53%. Median
(IQR) age: 20 years (1822). CDC-stage C was observed in 27 (79%);
50% had ]1 comorbidities including 3 with HCV co-infection. Drug
abuse was observed in 6 (13%). The median of prior ARV regimens
was 3 (35). Current ARV regimen included: PI: 87%, NNRTI:
27%, INSTI: 20%, enfuvirtide: 7% and CCR5 inhibitor: 4%. Median
CD4 T-cell count: 568 cells/mL (279771). Viral load B50 copies/
mL: 80%. Sixty percent (27/45) had ]1 co-medications (median 1).
The most frequent co-medications were NSAIDs (40%), hormonal
therapy (19%) and antimicrobials (19%). Use of herbal supplements was observed in 10 (22%). Overall, 23 (51%) had ] 1 CSDDIs:
19/27 (70%) with co-medication (orange flag 18 and red
flag 1); and 2/10 (20%) with herbal supplements. ARVARV
interactions were observed in 4/45 (9%): unboosted atazanavir
tenofovir (n 2), unboosted atazanavirefavirenz (n 1) and
lopinavir/ritonavirefavirenz (n 1) (all orange flag). Considering
patients with CSDDIs, 6 (26%) had a CSDDI that could reduce ARV
levels.
Conclusions: In this pilot study, a high prevalence of comorbidities,
co-medications and CSDDIs was observed in PHA. A considerable
proportion of patients had CSDDIs with a potential to cause subtherapeutic ARV levels, what could be a concern in patients
harbouring drug-resistance viruses. Therefore, clinicians should be
aware of comorbid conditions pharmacologic management in order
to avoid CSDDIs with ARVs agents.
Tolerability is more important than simplicity for treatment
durability
Benoit Trottier1; Nima Machouf2; Emmanuelle Huchet3;
Stephane Lavoie4; Sylvie Vezina5; Michel Boissonnault4;
Louise Charest4; Marie Munoz4; Danielle Legault4; Daniele Longpré4
and Réjean Thomas6
1
Clinical Research, Clinique Médicale l’Actuel, Montreal, Canada.
2
Epidemiology, Clinique Médicale l’Actuel, Montreal, Canada.
3
Interim Clinical, Clinique Médicale l’Actuel, Montreal, Canada.
4
Medicine, Clinique Médicale l’Actuel, Montreal, Canada. 5Clinical,
Clinique Médicale l’Actuel, Montreal, Canada. 6Clinique Médicale
l’Actuel, Montreal, Canada.
Introduction: Many studies have shown the superiority of single
tablet regimens (STRs) of antiretrovirals for the treatment of HIV in
terms of efficacy, adherence and rate of hospitalisation as they offer
a low pill burden and once daily dosing. Our objective was to
compare the duration of first-line STRs to multi-tablet regimens.
Methods: From our clinical database, we selected patients initiating
any of the major first-line regimens between 2007 and 2013. Two
STRs, Atripla (ATP) and Complera (CPLR), were compared to three
non-STRs: two NRTIs and raltegravir (RAL), atazanavir/ritonavir (ATV/
r) or darunavir/ritonavir (DRV/r). The primary outcome was time to
discontinuation of the first-line regimen. The association between
regimen type and duration was estimated using Cox proportional
hazards models adjusted for age, gender, baseline CD4, baseline viral
load, risk factor, site and year of treatment initiation.
Results: A total of 743 patients (281 on STRs and 462 on non-STRs)
were included. 693 (93%) were male and median age was 43 years.
Median length of follow-up was 3.2 years. 56% of patients were
MSM, 6% IDU and 6% from endemic countries. Patients on an STR
were less likely to be IDU (pB0.024) and have a baseline HIV-RNA
]100,000 copies/mL (p B0.011). Overall, 321 (43%) patients
discontinued their regimen during the study period. The rate of
discontinuation one year after starting ARV depends on the regimen:
29% for patients on 2NRTIsDRV/r, 26% on ATP, 25% on 2NRTIs
ATV/r, 17% on 2NRTIsRAL and 10% on CPLR (p B0.001). In the
adjusted model, durability for STR and non-STR was equivalent
(aHR 0.83, p 0.108). Compared to patients on ATP, patients on
CPLR were less likely to discontinue (HR 0.58, p0.070). No
difference between ATP and the other regimens was observed: HR
165
Poster Abstracts
for 2NRTIsRAL 0.92 (p0.66), 2NRTIs DRV/r 1.16 (p
0.36), 2NRTIsATV/r 1.11 (p 0.46).
Conclusions: Our findings suggest that STRs do not necessarily result
in a more durable treatment. Even with a higher pill burden and/or
twice daily dosing, patients initiating therapy with RAL or boosted-PI
based regimens were not more likely to discontinue the first-line
regimen compared to patients on an STR. Among the STR subgroups,
the regimen with better known tolerability conferred more durable
treatment. Limitations included our inability to adjust for the
patient’s adherence to a given regimen.
P234
Can we trust the guidelines? Comparison between the data
presented and the recommendations of the International
Antiviral Society-USA Panel
Rein Jan Piso
Medizinische Klinik, Kantonsspital Olten, Olten, Switzerland.
Introduction: Clinicians often do not have the time and possibilities
to read all scientific evidence necessary to maintain high quality
patient care. They rely on guidelines made by experts to help them in
their daily work.
Methods: We compared the 2012 recommendations and the
arguments of the IAS-USA Panel with the data referenced and
presented with the original data of the studies. Special topic was the
timing of antiretroviral therapy. Only studies included in the guideline text were analyzed.
Results: There is a large discrepancy between the data and the
recommendations concerning early antiviral therapy. The studies are
either not designed to answer this question or the data is not
sufficient to support the arguments. The authors highlight benefits
without mention of side effects or other problems. Neither in trans-
mission rates, nor mortality, AIDS events, co-morbidities (hepatitis B
and C excluded) or decreasing the risk of malignancy, the data
presented support early therapy.
Conclusions: A large discrepancy between the underlining data and
the recommendation made by the IAS-USA Panel exists concerning
early antiviral therapy.
References
1. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC,
Kumarasamy N, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365(6):493505.
2. HIV-CAUSAL Collaboration. When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in
HIV-infected persons in developed countries: an observational study.
Ann Intern Med. 2011;154(8):50915.
3. Writing Committee for the CASCADE Collaboration. Timing of
HAART initiation and clinical outcomes in human immunodeficiency
virus type 1 seroconverters. Arch Intern Med. 2011;171(17):15609.
4. Opportunistic Infections Project Team of the Collaboration of
Observational HIV Epidemiological Research in Europe (COHERE) in
EuroCoord. CD4 cell count and the risk of AIDS or death in HIVInfected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE. PLoS
Med. 2012;9(3):e1001194.
5. van Lelyveld SF, Gras L, Kesselring A, Zhang S, De Wolf F, Wensing
AM, et al. Long-term complications in patients with poor immunological recovery despite virological successful HAART in Dutch
ATHENA cohort. AIDS. 2012;26(4):46574.
6. Silverberg MJ, Chao C, Leyden WA, Xu L, Horberg MA, Klein D,
et al. HIV infection, immunodeficiency, viral replication, and the risk
of cancer. Cancer Epidemiol Biomarkers Prev. 2011;20(12):25519.
7. Ho JE, Scherzer R, Hecht FM, Maka K, Selby V, Martin JN, et al. The
association of CD4 T-cell counts and cardiovascular risk in treated
HIV disease. AIDS. 2012;26(9):111520.
Arguments of committee
ART reduces 96% of transmissions
Comment
Absolute reduction 0.9 to 0.1 in 100 person years
Reference
[1]
82% of transmissions in Africa, and 73% of the linked
Increase of 38% of AIDS events, if started B350 B500
transmissions in o
Absolute increase of AIDS events from 1.78 to 3.63% for a time
[2]
CD4 cells
ART implementation B500 CD4 cell/uL associated with
period of five years, no reduction in mortality
Absolute decrease of AIDS Events from 1.17 to 0.98/100 person
[3]
slower disease progression
Higher CD4 cell count associated with decreased risk of AIDS
and death in viral suppressed patients up to 500 CD4 cells
Lower CD4 nadir leads to poor recovery and increased
years,
Absolute increase of AIDS event or death increase from 0.79 to 1.2
[4]
per 100 py
Only patients with CD4-Nadir B200/uL were included
[5]
morbidity and mortality
41% reduction of serious WHO stage 4 events, pulm. tuberculosis Absolute increase from 2.4 to 3.96/100 py early vs non-early
bacterial infection and death treated vs non-treated early
treated
[1]
Patients with CD4 cells 500 has an identical risk of cancer
Only comparison 200-499 and 500 CD4 cells, no data on
[6]
compared to non-HIV
Cross-section studies suggest a benefit of early ART on
patients 350-499 CD4 cells
Only arterial flow mediated dilatation measured. Only comparison
cardiovascular risk
Renal disease increased at lower CD4 counts
Communities with high ART use have lower rates of new
[7,8]
between B350 and 350 CD4 cells.
Risk of renal disease increases only if CD4 cells fall below 200 cell/uL
Significant overall, but not if only data from 2004 to 2009 are
infections
analyzed, with an increase of ART of 50%. Overall significance
Decreasing ‘‘community viral load’’ accompanied by decreasing No comment
[9]
[10]
[11]
incidence of new HIV infection
166
Poster Abstracts
8. Seaberg EC, Benning L, Sharrett AR, Lazar JM, Hodis HN, Mack WJ,
et al. Association between human immunodeficiency virus infection
and stiffness of the common carotid artery. Stroke. 2010;41(10):
216370.
9. Islam FM, Wu J, Jansson J, Wilson DP. Relative risk of renal disease
among people living with HIV: a systematic review and meta-analysis.
BMC Public Health. 2012;12:234.
10. Montaner JS, Lima VD, Barrios R, Yip B, Wood E, Kerr T, et al.
Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia,
Canada: a population-based study. Lancet. 2010;376(9740):5329.
11. Das M, Chu PL, Santos GM, Scheer S, Vittinghoff E, McFarland W,
et al. Decreases in community viral load are accompanied by
reductions in new HIV infections in San Francisco. PLoS One. 2010;
5(6):11068.
three clinical trials (Studies 102 and 103) elvitegravir/cobicistat/
emtricitabine/tenofovir DF (E/C/F/TDF; STB) had non-inferior efficacy
and favourable safety vs efavirenz/emtricitabine/tenofovir DF (EFV/
FTC/TDF; ATR) or ritonavir-boosted atazanavir (ATVRTV)FTC/
TDF (TVD) in HIV-infected, treatment-naı̈ve subjects at Week 144.
The efficacy and safety of STB in subjects B or ]50 yrs is
described.
Materials and Methods: Post hoc analysis of efficacy, tolerability and
safety in subjects B or ]50 yrs at Week 144.
Results: Subjects ]50 yrs in Study 102: STB: 14% (49/348), ATR: 16%
(56/352); in Study 103: STB: 14% (48/353), ATVRTVTVD: 14%
(48/355). Efficacy, safety and tolerability by age and study endpoint
are shown in Table 1. Regardless of age, STB had robust efficacy at
Week 144 with similar virologic outcomes vs ATR or ATV
RTVTVD. Discontinuations (DC) due to AE on STB were similar
to the comparators, most occurred by Week 48. Median changes
in eGFR on STB were similar by age; DC with renal PRT was rare
[STB: 4 (0.6%); ATV: 3 (0.8%); ATR: 0], 2 and 1 in ]50 yrs old strata,
respectively.
Conclusions: STB compared to ATR or ATVRTVTVD, is an
efficacious, well-tolerated and safe regimen for HIV-1-infected, treatment-naı̈ve subjects Bor ]50 yrs of age.
P235
Long-term efficacy and safety of E/C/F/TDF vs EFV/FTC/TDF
and ATVRTVFTC/TDF in HIV-1-infected treatment-naı̈ve
subjects ]50 years
Brian Gazzard1; Pierre Marie Girard2; Giovanni Di Perri3;
Joel Gallant4; William Towner5; Felipe Rogatto6; Jennifer Demorin7;
Damian McColl7; Hui Liu8; Martin Rhee9; Javier Szwarcberg9 and
David Piontkowsky7
1
Infectious Disease, Chelsea and Westminster Hospital, London, UK.
2
Infectious Diseases, Center Hospital at University St Antoine, Paris,
France. 3Internal Medicine, School of Medicine, University of Turin,
Torino, Italy. 4Infectious Diseases, Southwest CARE Center, Santa Fe,
NM, USA. 5Internal Medicine, Kaiser Permanente, Los Angeles, CA,
USA. 6Medical Affairs, Gilead Sciences Europe, Stockley Park, UK.
7
HIV Medical Affairs, Gilead Sciences, Foster City, CA, USA. 8Biostats,
Gilead Sciences, Foster City, CA, USA. 9Clinical Research, Gilead
Sciences, Foster City, CA, USA.
P236
Treatment modification in HIV-Infected individuals starting
antiretroviral therapy between 2011 and 2014
Michaela Rappold1; Armin Rieger2; Andrea Steuer3; Maria Geit4;
Mario Sarcletti1; Bernhard Haas5; Ninon Taylor6;
Manfred Kanatschnig7; Gisela Leierer1; Bruno Ledergerber8 and
Robert Zangerle1
1
Department of Dermatology and Venereology, Innsbruck Medical
University, Innsbruck, Austria. 2Department of Dermatology and
Venereology, Medical University of Vienna, Vienna, Austria.
3
Department of Pulmonary Medicine, Otto Wagner Hospital, Vienna,
Vienna, Austria. 4Department of Dermatology and Venereology,
Allgemeines Krankenhaus Linz, Linz, Austria. 5Department of
Introduction: In high-income countries, ]30% of HIV-infected
patients are ]50 years (yrs) old (UNAIDS 2013). In two phases,
Efficacy, safety and tolerability by age
Week
Week
Week
Week
Week
Week
48 B50
48]50
96B50
96 ]50
144 B50
144 ]50
Virologic success (VS)
263 (88); 250 (84)
42 (86); 46 (82)
253 (85); 241 (81)
40 (82); 46 (82)
241 (81); 221 (75)
38 (78); 44 (79)
Virologic failure (VF)
23 (8); 23 (8)
2 (4); 2 (4)
20 (7); 24 (8)
2 (4); 3 (5)
23 (8); 30 (10)
3 (6); 4 (7)
Mean change in CD4,
cells/mm3
246; 208
199; 194
305; 278
233; 250
325; 304
295; 280
n (%)
STB versus ATR
AEs Leading to DC
10 (3); 12 (4)
3 (6); 6 (11)
12 (4); 18 (6)
5 (10); 6 (11)
16 (5); 20 (7)
5 (10); 6 (11)
Median change in
14.8; 1.6
12.0; 7.5
13.9; 0.4
12.9; 8.2
15.2; 0.3
18.2; 8.7
271 (89); 266 (87)
45 (94); 42 (88)
251 (82); 249 (81)
43 (90); 43 (90)
236 (77); 228 (74)
38 (79); 37 (77)
17 (6); 17 (6)
212; 213
2 (4); 2 (4)
176; 200
22 (7); 25 (8)
261; 266
2 (4); 1 (2)
226; 231
25 (8); 25 (8)
285; 300
3 (6); 1 (2)
245; 256
eGFRCG, mL/min
STB versus ATV
RTVTVD
VS
VF
Mean change in CD4,
cells/mm3
AEs Leading to DC
12 (4); 15 (5)
1 (2); 3 (6)
13 (4); 17 (6)
2 (4); 4 (8)
17 (6); 21 (7)
4 (8); 9 (19)
Median change in
13.4; 10.0
10.2; 7.3
12.5; 8.8
11.1; 12.6
12.9; 9.4
13.5; 12.9
eGFRCG, mL/min
167
Poster Abstracts
Abstract P236Table 1. Uni- and multivariable Cox regression: association between different baseline characteristics and
modifications of the initial ART regimen
Univariable Cox Regression
Multivariable Cox Regression
Hazard ratio
95% CI
Hazard ratio
95% CI
B30 years
0.98
0.681.42
0.98
0.661.47
3050 years
0.89
0.631.26
0.89
0.621.27
1
Reference
1
Reference
Male injecting drug user
1.62
1.142.29
1.45
1.022.06
Female injecting drug user
0.91
0.461.78
0.82
0.411.62
Male heterosexual
1.01
0.751.36
0.89
0.651.21
Female heterosexual
1.28
0.941.73
0.98
0.721.34
Other
0.78
0.411.48
0.54
0.281.04
Men who have sex with men
1
Reference
1
Reference
Age
]50 years
Drugs/Regimen
RPV
0.15
0.060.42
0.16
0.060.45
EFV
1.04
0.701.54
1.03
0.691.54
ATV
1.75
1.272.42
1.68
1.212.32
RAL
1.20
0.771.88
1.09
0.691.72
Other
2.98
2.224.01
3.10
2.304.18
DRV
1
Reference
1
Reference
1.73
1
1.242.40
Reference
1.68
1
1.192.37
Reference
AIDS at baseline
Yes
No
Infectious Diseases, Landeskrankenhaus Graz West, Graz, Austria.
6
Department of Internal Medicine III, Paracelsus Medical University
Salzburg, Salzburg, Austria. 7Department of Internal Medicine,
Landeskrankenhaus Klagenfurt, Klagenfurt, Austria. 8Division of
Infectious Diseases, University Hospital Zurich, Zurich, Switzerland.
Introduction: While antiretroviral therapy (ART) has increased the
survival of HIV patients and turned HIV infection into a chronic
condition, treatment modifications and poor adherence might limit
this therapeutic success.
Methods: Patients from the Austrian HIV Cohort Study, who started
their first ART after Rilpivirine became available in February 2011,
were analyzed for factors associated with treatment modification
which could be either a change of drugs or a stop of the regimen. A
drug was considered as stopped when the regimen was interrupted
for more than eight days. Drugs of particular interest were Darunavir
(DRV), Atazanavir (ATV), Raltegravir (RAL), Rilpivirine (RPV) and
Efavirenz (EFV). RPV and EFV were analyzed only when taken as
single tablet regimen. Other drugs were summarized as ‘‘other.’’
Proportional hazards regression methods were used to identify
predictors of discontinuation and KaplanMeier estimates were used
to calculate probabilities of discontinuation. Patients who died were
censored at the date of death.
Results: 965 patients started ART, 282 with DRV, 161 with ATV, 96
with RAL, 108 with RPV and 118 with EFV. Median time for taking
initial ART is 11.6 months. 322 (33.4%) patients modified their initial
ART. The overall probability of modification at one year was 28.7%,
at two years 40.0% and at three years 49.8%. In a multivariable
proportional hazards regression analysis, AIDS diagnosis at baseline
and injecting drug use (IDU) of men compared with men who have
sex with men (MSM) have a higher risk of switch/stop. Compared
with DRV, RPV showed a much lower and ATV and particularly
‘‘other’’ a higher risk for discontinuation (Table 1).
Availability of more effective/convenient treatment (28.9%) was the
main reason for discontinuation, especially in the group ‘‘other’’
(43.5%), RAL (34.6%) and DRV (31.6%). Non-specified patient or
physician wish to modify therapy was revealed in 17.4% and 9.3%
respectively. EFV was modified in 52.8% due to central nervous
system toxicity and ATV in 27.8% for gastrointestinal toxicity
including hyperbilirubinemia.
Conclusion: Rates of modification and interruption were still high in
recent years, particularly in the first year of ART. The decreased rate
of modification found in patients treated with Rilpivirine may be
attributed to selection of patients according to guidelines.
P237
Increased risk of virological failure to the first antiretroviral
regimen in HIV-infected migrants compared to natives: data
from the ICONA cohort
Annalisa Saracino1; Patrizia Lorenzini2; Sergio Lo Caputo3;
Enrico Girardi4; Francesco Castelli5; Paolo Bonfanti6; Massimo Galli7;
Pietro Caramello8; Nicola Abrescia9; Cristina Mussini10;
Laura Monno1 and Antonella d’Arminio Monforte11
1
Clinic of Infectious Diseases, University of Bari, Bari, Italy
2
‘‘L. Spallanzani’’ IRCCS, Rome, Italy. 3Clinic of Infectious Diseases,
Santissima Annunziata Hospital, Florence, Italy. 4Department of
Epidemiology, National Institute for Infectious Diseases
‘‘L. Spallanzani’’ IRCCS, Rome, Italy. 5Division of Infectious and
Tropical Diseases, Civili General Hospital, University of Brescia
and Spedali Brescia, Italy. 6Department of Infectious Diseases,
Azienda Ospedaliera Lecco, Lecco, Italy. 7Department of
168
Poster Abstracts
Abstract P237Table 1. Characteristics of migrant and native-born HIV-positive antiretroviral naı̈ve patients enrolled in the ICONA
cohort during the period 20042014 at time of inclusion
Migrants
Total n 5777
n 1179
Male gender, n (%)
Age, yrs, median (IQR)
Education, n (%)
Employment, n (%)
B0.001
34 (2840)
355 (30.1%)
39 (3247)
1075 (17.3%)
B0.001
B0.001
High
309 (26.2%)
1980 (43.1%)
Missing
515 (43.7%)
1543 (33.6%)
Full employed
444 (37.7)
2786 (60.5%)
Less than high
353 (30.0%)
554 (14.5%)
229 (19.4%)
1180 (25.7%)
Heterosexual
Homosexual
703 (59.6%)
312 (26.5%)
1634 (35.5%)
2194 (47.7%)
48 (4.1%)
436 (9.5%)
334 (7.3%)
No
904 (76.7%)
3352 (72.9%)
Yes
21 (1.8%)
149 (3.2%)
Unknown
254 (21.5%)
1097 (23.9%)
No
677 (57.4%)
1757 (38.2%)
Yes
Unknown
252 (21.4%)
250 (21.2%)
1780 (38.7%)
1061 (23.1%)
51 (4.3%)
17 (0.4%)
B0.001
B
203 (17.2%)
1344 (29.2%)
B0.001
Non-B
218 (18.5%)
316 (6.9%)
Unknown
First CD4 count (per 100 cell/mmc more)
758 (64.3%)
0.005
B0.001
2938 (63.9%)
4.5 (IQR 3.75.2)
1.6 (IQR 3.95.2)
317 (IQR 137509)
396 (223577)
B0.001
0.003
B200
200350
324 (27.5%)
226 (19.2%)
876 (19.1%)
732 (15.9%)
350
440 (37.3%)
2197 (47.8%)
Missing
189 (16.0%)
793 (17.3%)
AIDS event pre-treatment, n (%)
HCV co-infection, n (%)
B0.001
116 (9.8%)
First HIV RNA (per 1 log cp/mL more)
First CD4, cell/mmc
B0.001
78 (1.7%)
Other/missing
Pregnancy status, n (%)
HIV subtype, n (%)
99 (8.4%)
Unemployed
Other/unknown
Smoke, n (%)
n4598
3914 (85.1%)
IVDU
Recent drug use, n (%)
p
674 (57.2%)
Occasionally employed
Mode of HIV transmission, n (%)
Natives
0.066
140 (11.9%)
362 (7.9%)
B0.001
71 (6.0%)
446 (9.7%)
B0.001
Negative
794 (67.3%)
2882 (62.7%)
Positive
Unknown
314 (26.6%)
1270 (27.6%)
HBV co-infection, n (%)
Positive
Negative
58 (4.9%)
785 (66.6%)
144 (3.1%)
3060 (66.6%)
Unknown
336 (28.5%)
1394 (30.3%)
CMV co-infection, n (%)
Positive
45 (3.8%)
246 (5.3%)
Negative
492 (41.7%)
1579 (34.3%)
Unknown
642 (54.4%)
2773 (60.3%)
Infectious Diseases, L. Sacco University Hospital, University of Milan,
Milan, Italy. 8Department of Infectious Diseases, Amedeo di Savoia
Hospital, Turin, Italy. 9Department of Infectious Diseases, Cotugno
Hospital, Naples, Italy. 10Clinic of Infectious Diseases, University of
Modena and Reggio Emilia, Modena, Italy. 11Clinic of Infectious
Diseases, San Paolo Hospital, University of Milan, Milan, Italy.
Introduction: Aim of the study was to evaluate possible disparities in
access and/or risk of virological failure (VF) to the first antiretroviral
(ART) regimen for migrants compared to Italian-born patients and to
assess determinants of failure for the migrants living with HIV.
0.008
B0.001
Methods: All native and migrant naı̈ve patients enrolled in ICONA in
20042014 were included. Firstly, variables associated to ART
initiation were analyzed. In a second analysis, the primary endpoint
was time to failure after at least six months of ART, defined as: (a) VF
(first of two consecutive viral load (VL) 50 and 200 copies/mL);
(b) treatment discontinuation (TD) for any reason; and (c) treatment
failure (TF: confirmed VL 200 cp/mL or TD). A Poisson multivariable analysis was performed to control for confounders.
Results: A total of 5777 HIV-pos ART-naı̈ve patients (1179 migrants
and 4598 natives) were evaluated. Most migrants were from subSaharan Africa (35.3%) and South-Central America/Caribbean (29%).
169
Median duration of residency in Italy was five years (IQR 110).
Baseline characteristics significantly differed between the two groups
(Table 1); in particular, lower CD4 counts and higher frequency of
AIDS events were observed in migrants vs natives. When adjusting for
baseline confounders, migrants presented a lower chance to initiate
ART compared to natives (OR 0.78, 95% CI 0.650.93, p0.006).
After ART initiation, the incidence rate of VF 50 cp/mL was 15.5 per
100 person-years (95% CI 12.818.8) in migrants and 8.9 in natives
(95% CI 7.99.9), respectively. By multivariable analysis, migrants had
a significantly higher risk of VF, both 50 cp/mL (OR 1.50, 95% CI
1.171.193, p0.001) and 200 cp/mL (OR 1.59, 95% CI 1.232.05,
pB0.001), and of TF (OR 1.15, 95% CI 1.001.32, p 0.045), while no
differences were observed in TD risk. Among migrants, variables
associated with a higher VF risk were age (for 10-year increase, OR
0.96, 95% CI 0.930.98, p0.002), unemployment (OR 1.96, 95% CI
1.203.20, p0.007) and use of a boosted PI based-regimen (OR
2.04, 95% CI 1.253.34, p0.005 vs NNRTI-based), while pregnancy
was associated with TD (OR 3.73, 95% CI 2.365.90, p B0.001) and TF
(OR 3.13, 95% CI 02.004.89, pB0.001).
Conclusions: Despite the use of more potent and safer antiretroviral
drugs in the last 10 years, and even in a setting of universal access to
ART, migrants living with HIV still present barriers to ART initiation
and increased risk of VF compared to natives.
P238
144-week outcomes of lopinavir/ritonavir (LPV/r)-based
first-line ART in 1,409 HIV-infected patients: data
from the German STAR/STELLA cohort
Eva Wolf1; Andreas Trein2; Axel Baumgarten3; Christoph Stephan4;
Hans Jaeger1; Heribert Hillenbrand5; Siegfried Koeppe6;
Thomas Lutz7; Bettina Koenig8 and Hans-Juergen Stellbrink9
1
HIV Research and Clinical Care Centre, MVZ Karlsplatz, Munich,
Germany. 2HIV Center (Drs A. Schaffert/E. Schnaitmann/A. Trein),
Stuttgart, Germany. 3HIV Practice (Drs S. Dupke/A. Baumgarten/A.
Carganico), Berlin, Germany. 4HIV Center, University Hospital
Frankfurt, Goethe University, Frankfurt, Germany. 5MVZ
PraxisCityOst (Drs. H. Hillenbrand, H. Karcher), Berlin, Germany.
6
Gemeinschaftspraxis (Drs S. Koeppe/P. Kreckel), Berlin, Germany.
7
Infektiologikum Frankfurt-City, Frankfurt am Main, Germany.
8
Medical Department, AbbVie Deutschland GmbH & Co. KG,
Wiesbaden, Germany. 9Study Center, Infektionsmedizinisches
Centrum Hamburg, Hamburg, Germany.
Introduction: STAR/STELLA is a prospective[TS1] cohort of HIV
patients initiated on LPV/r-based ART in routine clinical practice.
Here, virologic/immunologic outcomes and safety data of LPV/rbased first-line ART over a period of 144 weeks are presented.
Methods: Analysis included ART-naı̈ve patients who started on
LPV/r before July 2011 (i.e. patients with ]144 weeks since ART
initiation). Safety evaluation included adverse events (AEs), discontinuations (disc.) due to AEs, and symptoms assessed with the selfreport ACTG Symptom Distress Module (ASDM; high scorehigh
distress).
Results: 1409 patients were included (84% men; 76% on TDFFTC),
with a large proportion in advanced stages of HIV disease at ART
initiation: 48% had a CD4 count B200/mL, 55% had HIV RNA levels
100,000 c/mL. 53% of patients (n746) remained on LPV/r for at
least 144 weeks. Time on drug was longer for patients initiated
before 2008 than in subsequent years (HRadj, 1.2; 95% CI, 1.01.4;
p0.04; hazard ratio adjusted for CD4 B200/mL and HIV RNA
100,000 c/mL). Main reasons for d/c were: AEs (19.3%), patient
wish (9.2%), virologic/immunologic failure (4.1%), and noncompli-
Poster Abstracts
Abstract P238Figure 1. Time to CD4 count >750 c/mL, stratified
by BL CD4 count.
ance (2.8%); 1.6% of patients died. By week 144, 33% of patients had
750 CD4/mL (KaplanMeier estimate): time to CD4 count 750 c/
mL, stratified by BL CD4 count, is shown in Figure 1.
ITT snapshot analysis of HIV RNA B50 c/mL at week 144 showed
51% responders (failure d/c due to virologic/immunologic failure,
AEs, noncompliance, death). In patients on LPV/r for 144 weeks,
median CD4 change was 314/mL (IQR, 205440/mL), 87% had HIV
RNA levels B50 c/mL. In patients who discontinued therapy prior to
week 144, 56% had an HIV RNA level B50 c/mL. In 51% of patients,
]1 AE was reported (most commonly diarrhoea, 35%); 11% of
patients had ]1 AE of grade 3 or 4 (diarrhoea, 4.5%). In patients
who remained on LPV/r based ART through 144 weeks, median
ASDM score decreased significantly from 9 at BL (IQR, 321) to 2.5 at
Week 144 (IQR, 08.5, pB0.001).
Conclusion: In the STAR/STELLA observational cohort, LPV/r-based
ART demonstrated good virologic outcomes and immune recovery in
ART-naı̈ve patients over 144 weeks, with significant improvements in
symptom distress. Over three years, B5% of patients discontinued
LPV/r due to virologic/immunologic failure, and 19% of patients
discontinued for tolerability reasons.
P239
An observational comparison of first-line combination
antiretroviral treatment (cART) with 2NRTI and ATV/r or
DRV/r in HIV-infected patients in Italy
Alessandro Cozzi-Lepri1; Andrea Antinori2; Stefano Bonora3;
Antonella Cingolani4; Giovanni Cassola5; Gioacchino Angarano6;
Vincenzo Vullo7; Cristina Mussini8; Andrea Gori9; Franco Maggiolo10;
Antonella Castagna11 and Antonella d’Arminio Monforte on behalf of
the ICONA Foundation Study12,13
1
UK. 2Infectious Diseases, INMI Spallanzani Hospital, Rome, Italy.
3
Infectious Diseases, University of Turin, Turin, Italy. 4Faculty of
Medicine, Cattolica Sacro Cuore University, Rome, Italy. 5Infectious
Diseases, Galliera Hospital, Genova, Italy. 6Biomedical Science,
University of Bari, Bari, Italy. 7Public Health and Infectious Diseases,
Sapienza University of Rome, Rome, Italy. 8Infectious Diseases,
University of Modena, Modena, Italy. 9Infectious Diseases, San
Gerardo University of Monza, Monza, Italy. 10Infectious Diseases,
Ospedali Riuniti Bergamo, Bergamo, Italy. 11Infectious Diseases,
San Raffaele Hospital, Milan, Italy. 12Health Sciences, San Paolo
Hospital, Milan, Italy. 13Health Sciences, University of Milan,
Milan, Italy.
170
Poster Abstracts
Introduction: In a recent clinical trial (ACTG 5257), no difference in
viral failure (VF) of a first-line cART containing atazanavir/r (ATV/r) or
darunavir/r (DRV/r) was found [1]. For the endpoint of discontinuation due to intolerance, the regimen with DRV/r was superior to that
of ATV/r (49% of the stops of ATV/r were attributed to jaundice or
hyperbilirubinemia). These and other intolerances to ATV/r remain a
concern for clinicians.
Methods: Participants in the ICONA Foundation Study who started
cART with 2NRTI ATV/r or DRV/r while ART-naı̈ve were included.
Several endpoints were evaluated: confirmed VF200 copies/mL
after six months of therapy, discontinuation of DRV/r or ATV/r for any
reasons or because of intolerance/toxicity (as reported by the
treating physician) and the combined endpoint of VF or stop.
Survival analysis with KaplanMeier curves and Cox regression
model stratified by clinical site was used. Patients’ follow-up accrued
from cART initiation to the date of the event or to the date of last
available visit/viral load.
Results: 894 patients starting 2NRTIATV/r and 686 2NRTIDRV/r
when ART-naı̈ve on average in 2011 (IQR: 20102012) were studied.
Most common NRTIs used were FTC/TDF (84%) and ABC/3TC (12%).
Median age was 40 years, 22% females, 44% heterosexuals. Patients
starting ATV/r were more likely to be hepatitis B/C infected (2% and
14% vs 1% and 9%, p0.001), they started one year earlier (2011 vs
2012, p0.001), were more likely to be enrolled in sites located in
the north of Italy (63% vs 54%, p 0.04), started cART less promptly
after HIV diagnosis (5 vs 2 months, p 0.02) and less likely to have
started TDF/FTC (83% vs 85%, p0.02). By two years of cART, 9.8%
(95% CI 7.612.0) of those starting ATV/r experienced discontinuation due to intolerance/toxicity vs 6.5% in DRV/r group (95% CI 4.2
8.8, p0.04). After controlling for several potential confounders
(age, gender, nation of birth, mode of HIV transmission, hepatitis coinfection status, AIDS diagnosis, nucleoside pair started, baseline CD4
count and viral load and year of starting cART) the relative hazard
(RH) for ATV/r vs DRV/r was 2.01 (95% CI 1.23, 3.28, p 0.005). There
were no statistical differences detected for any of the other
outcomes.
Conclusions: Although unmeasured confounding cannot be ruled
out, our results seem to be consistent with those of the ACTG 5257.
When all cause discontinuations were considered, or the composite
endpoint of treatment failure, there was no difference between ATV/
r- and DRV/r-based regimens.
Reference
1. Landovitz RL, Ribaudo HJ, Ofotokun I, Wang H, Baugh BP, Leavitt
RY, et al. Efficacy and tolerability of atazanavir, raltegravir, or
darunavir with FTC/tenofovir: ACTG 5257. CROI 2014. Conference
on Retroviruses and Opportunistic Infections; 2014 March 36;
Boston. Abstract 85.
P240
Phase IIIb, open-label single-arm trial of darunavir/
cobicistat (DRV/COBI): Week 48 subgroup analysis of
HIV-1-infected treatment-nave adults
Karen Tashima1; Gordon Crofoot2; Frank L Tomaka3; Thomas N
Kakuda3; Anne Brochot4; Simon Vanveggel5; Magda Opsomer5;
William Garner6; Nicolas Margot6; Joseph M Custodio6; Marshall W
Fordyce6 and Javier Szwarcberg6
1
The Miriam Hospital, Providence, RI, USA. 2Gordon Crofoot
Research, Houston, TX, USA. 3Janssen Research & Development, LLC,
Titusville, FL, USA. 4Janssen Research & Development, LLC, Beerse,
Belgium. 5Janssen Infectious Diseases BVBA, Beerse, Belgium. 6Gilead
Sciences, Foster City, CA, USA.
Introduction: COBI, a PK enhancer with no ARV activity is a more
selective cytochrome P450 (CYP)3A inhibitor than ritonavir (RTV),
does not induce CYP isozymes, and thus has less potential for drugdrug interactions. COBI boosts DRV PK as effectively as RTV in
healthy volunteers.
Materials and Methods: This 48-week, phase IIIb, open-label, singlearm, US multicentre study (NCT01440569) included HIV-infected
treatment-nave and experienced adults with no DRV RAMs, viral load
(VL) ]1000 c/mL, eGFR ]80 mL/min and genotypic sensitivity to
investigator-selected N[t]RTIs. Patients received DRV/COBI 800/150
mg qd (as single agents) plus two fully active N[t]RTIs. The primary
endpoint was any treatment-emergent grade 3 or 4 AEs through
Week 24. We report 48-week safety, efficacy and PK/PD results in
treatment-nave patients.
Results: Of 313 ITT patients, 295 were treatment-nave (94%). In the
treatment-nave cohort, 90% were male, 60% white and 294 (99.7%)
received a TDF-containing regimen. Median baseline (BL) VL was 4.8
log10 c/mL and CD4 370 cells/mm3.Treatment-emergent grade 3 or 4
AEs regardless of causality were reported in 21 (7%) patients. AEs
regardless of causality (any grade; ]10% of patients) were: diarrhoea
(27%), nausea (23%), URTI (15%) and headache (12%). Sixteen (5%)
patients had AEs leading to study drug discontinuation, most frequently rash (three patients), hypersensitivity and nausea (two patients each). Consistent with the known inhibition of tubular creatinine
secretion by COBI, there was a mean increase from BL in serum
creatinine by week 2 (0.09 mg/dL), remaining stable through week 48
(mean 0.10 mg/dL increase from BL). At week 48, 83% of patients
achieved VL B50 c/mL; FDA Snapshot); median increase in CD4 was
169 cells/mm3. Eight patients met the criteria for resistance testing.
M184V was detected in one pt receiving FTC. New primary RAMs were
not detected in the other seven patients. The mean population PKderived DRV AUC24h was 100,620 ng.h/mL and C0h 2,105 ng/mL
(n 281). There were no clinically relevant relationships between DRV
exposure and virologic response, AEs or laboratory parameters.
Conclusions: The DRV PK of DRV/COBI was consistent with historical
data for DRV/RTV. DRV/COBI 800/150 mg qd plus two N(t)RTIs had
Relative hazards of reaching the various defined outcomes from fitting a Cox regression model
Outcomes
Unadjusted RH (95% CI)
p
Adjusted RH (95% CI)
p
ATV/r vs. DRV/r
1.18 (0.97, 1.43)
0.09
1.16 (0.92, 1.47)
0.20
Discontinuation due to toxicity
ATV/r vs. DRV/r
1.48 (0.98, 2.22)
0.06
2.01 (1.23, 3.28)
0.005
3.49 (1.89, 6.43)
B.001
1.63 (0.75, 3.54)
0.22
1.25 (1.02, 1.52)
0.03
1.14 (0.90, 1.45)
0.27
All cause discontinuation
VF 200 copies/mL
ATV/r vs. DRV/r
VF 200 copies/mL or discontinuation
ATV/r vs. DRV/r
171
Poster Abstracts
an 83% response and was well tolerated through Week 48. These
results are similar to published data for DRV/RTV 800/100 mg qd,
and support the use of DRV/COBI 800/150 mg qd in treatment-nave
patients.
P242
Gaetana Sterrantino1; Mauro Zaccarelli2; Francesca Prati3;
Andrea Boschi4; Laura Sighinol5 and Vanni Borghi6
1
Tropical and Infectious Diseases Unit, Azienda OspedalieraUniversitaria Careggi, Florence, Italy. 2Viral Immunodeficiency Unit,
INMI ‘‘L Spallanzani’’ IRCCS, Rome, Italy. 3Infectious Diseases Unit,
IRCCS Santa Maria Bianca, Reggio Emilia, Italy. 4Infectious Diseases
Unit, Azienda Sanitaria di Rimini, Rimini, Italy. 5Infectious Diseases
Unit, Azienda Ospedaliera-Universitaria di Ferrara, Ferrara, Italy.
6
Infectious Diseases Unit, Azienda Ospedaliera-Universitaria di
Modena, Modena, Italy.
P241
Effectiveness and tolerability of abacavir-lamivudinenevirapine (ABC/3TC/NVP) in a multicentre cohort of
HIV-infected, ARV-naı̈ve patients
Daniel Podzamczer1; Jhon Fredy Rojas2; Isabel Neves3; Elena Ferrer1;
Josep M Llibrea4; Manuel Leal5; Miguel Gorgolas6; Ma Jose Crusells7;
Josep Ma Gatell2; Ricardo Correia Abreu3; Jordi Curto1;
Pere Domingo8; Ma Pilar Barrufet9 and Nerea Rozas1
1
Infectious Diseases, Hospital Universitari de Bellvitge, Barcelona,
Spain. 2Infectious Diseases, Hospital Clinic, Barcelona, Spain.
3
Infectious Diseases, Hospital Pedro Hispano ULS Matosinhos, EPE,
Porto, Portugal. 4Infectious Diseases, Hospital Germans Trias i Pujol,
Barcelona, Spain. 5Infectious Diseases, Hospital Universitario Virgen
del Rocio, Sevilla, Spain. 6Infectious Diseases, Fundacio Jimenez Diaz,
Madrid, Spain. 7Infectious Diseases, Hospital Clinico Universitario
Lozano Blesa, Zaragoza, Spain. 8Infectious Diseases, Hospital de la
Santa Creu i Sant Pau, Barcelona, Spain. 9Infectious Diseases,
Hospital de Mataro, Mataro, Spain.
Purpose: Very scarce information has been published to date with
the combination of ABC/3TC/NVP but it is currently being used in
clinical practice in Spain and Portugal. Our aim was to present the
clinical experience with this regimen in a cohort of adult HIV-infected
antiretroviral (ARV)-naı̈ve patients.
Methods: Retrospective, multicentre, cohort study. Consecutive adult
HIV-infected ARV-naı̈ve HLA-B*5701-negative patients, who started
ABC/3TC/NVP between 2005-2013, with at least one follow-up visit,
were included. Demographic, clinical and laboratory variables were
assessed at baseline, month 1, and every threefour months thereafter. The primary end point was HIV-1 viral load (VL)B40 c/mL at 48
weeks. Data were analyzed by intent-to-treat (ITT) (switchfailure,
and missing failure) and on treatment (OT) analyses.
Results: 78 patients were included. Median follow up was 26 (0.1-84)
months. 86% were male, median age 41 (23-69) years, 9% had AIDS,
8% were HCV, baseline CD4 was 275 (10-724) cells/mL and median
VL 4.58 (3.02-6.92) log. After 48 weeks, VL wasB40 c/mL in 89.8%
(OT), 79.7% (MF) and 65.4% (S F) and at 96 weeks in 88.5%,
78.9% and 61.6%, respectively. CD4 increased 246 (pB0.001) and
292 (pB0.001) cells/uL after 48 and 96 weeks, respectively. One
or more drugs of the regimen were discontinued in 33 (42.3%)
patients. In 15 (19.2%) patients (13 NVP, 2 ABC/3TC) therapy was
stopped due to toxicity after a median of one month (in only two
cases after six months of follow up): 80% of them had rash/liver
toxicity. Six (7.7%) patients discontinued ART due to virologic failure,
five (6.4%) because of other reasons and seven (9%) were lost to
follow-up. ALT but not AST significantly increased (0.07 ukat/L at
96 weeks, p 0.033). A significant increase of 25%, 26% and 42% in
total cholesterol, LDLc and HDLc, respectively, and a significant decrease in TC/HDL ratio (6%, p0.008) was observed after 96 weeks.
Conclusions: Despite a considerable proportion of patients had to
stop therapy due to toxicity (most associated with NVP), those
initially tolerating this regimen presented a high virologic and
immunologic response after 96 weeks, as well as a favourable lipid
profile. ABC/3TC/NVP may be a suitable alternative first regimen,
mainly in countries with economic constraints.
Four-drugs regimen containing raltegravir is highly effective
in HIV patients starting therapy with 500,000 copies/mL
viral load
Introduction: Assessing virological response of four-drugs antiretroviral regimen that include raltegravir (RAL) in naı̈ve patients with high
viral load ( 500,000 copies/mL) selected from a multicentre Italian
database.
Methods: Naı̈ve patients with HIV RNA 500,000 copies/mL, who
began standard antiretroviral regimens either based on non-nucleoside reverse transcriptase inhibitors (NNRTI) or boosted-PI (PI/r), or a
standard regimen plus RAL between 2008 and 2013 were analyzed.
Observation was censored at 12 months and the percentage of
patients who achieved a viral load below the limit of detection (BLD)
was calculated. Virological failure was defined as two consecutive
viral loads 40 copies/mL.
Results: Overall, 179 patients were included (13% with primary HIV
infection (PHI), and 42.5% with AIDS diagnosis). Of them, 156 started
standard three-drugs antiretroviral regimen (75.6% PI/r-based, 24.4%
NNRTI-based. Among patients with PHI, 23 patients (12.8%), 6 (25%)
started a four-drugs antiretroviral regimen containing both RAL and
PI/r. Patients’ characteristics were as follows: males 74%, median age
42 years (IQR 3551), sexually transmission 75.1%, median CD4 count
156 cells/mL (IQR 47368) and median HIV-RNA 6.1 log10 copies/mL
Abstract P242Figure 1. Probability of HIV viral load below the
limit of detection in naı̈ve HIV-1 patients with viral loads 500,000
copies/mL treated with a 4-drugs regimen containing raltegravir
versus standard therapy with PI/ or NNRTI.
172
(IQR 5.86.4). 91 of 179 patients (50.8%) reached BLD viral load
during the twelve months of observation. Three patients (1.7%) who
began regimens PI/r-based with three-drugs had virological rebound
after reaching BLD viral load. By use of survival analysis, we show
that those patients who added RAL to the standard regimen have
reached the primary end point faster (mean 8.4 months (95% CI 7.2
9.6) vs 11.4 (95% CI 11.011.8) in PI group and 10.3 (95% CI 9.411.1)
in NNRTI group; pB0.001, Figure 1). In the adjusted analysis, the
choice of a standard regimen versus a four-drugs regimen was driven
only by higher baseline viral load (OR. 9.05; 95% CI 2.4137.41;
p0.001).
Conclusions: Only half of the naı̈ve patients who began antiretroviral
therapy having 500,000 copies/mL HIV-RNA had virological success at 12 months. The success was reached faster using the RALcontaining four-drugs regimen, suggesting that strengthening the
initial regimen could be an option in patients with very high viral
load to improve virological response.
P243
Determinants of use of the fixed dose combination
emtricitabine/rilpivirine/tenofovir (Eviplera) in HIV-infected
persons receiving care in Italy
Alessandro Cozzi-Lepri1; Sergio Lo Caputo2; Franco Maggiolo3;
Andrea Antinori4; Adriana Ammassari4; Giulia Marchetti5;
Claudio Mastroianni6; Andrea Gori7; Giovanni Di Perri8;
Gioacchino Angarano9; Alessia Carbone10 and Antonella d’Arminio
Monforte5 on behalf of the ICONA Foundation Study11
1
Italy. 2Infectious Diseases Clinic, S. M. Annunziata Hospital, Firenze,
Italy. 3Infectious Diseases, Ospedali Riuniti Bergamo, Bergamo, Italy.
4
Infectious Diseases, INMI Spallanzani Hospital, Rome, Italy. 5Health
Sciences, San Paolo Hospital, Milan, Italy. 6Infectious Disease,
La Sapienza University Rome, Rome, Italy. 7Infectious Diseases,
San Gerardo University Monza, Monza, Italy. 8Infectious Diseases,
University of Turin, Turin, Italy. 9Biomedical Sciences,
University of Bari, Bari, Italy. 10Infectious Diseases, San Raffaele
Hospital, Milan, Italy. 11Health Sciences, University of Milan,
Milan, Italy.
Introduction: Emtricitabine/rilpivirine/tenofovir (EVP) is a fixed-dose
combination of antiretrovirals (ARV) approved by the European
Poster Abstracts
Medicines Agency in November 2011 and introduced in Italy in
February 2013. It is a once-a-day single tablet and is licensed in
Europe for use only in ARV-naı̈ve patients with a viral load (VL)
5100,000 copies/mL.
Objective: To identify factors that may be associated with the use of
EVP as first-line regimen in HIV-infected individuals starting cART
from ARV-naı̈ve in Italy.
Methods: Clinical sites in ICONA Foundation Study in which ]1
person had started EVP were selected for this analysis. From
these we included all patients who started an EVP-based cART
regimen as well as those starting other cART regimens after the date
of introduction of EVP at the site (after February 2013 in
any case) and with a VL 5100,000 copies/mL from ARV-naı̈ve.
Characteristics at the time of starting cART were compared using chisquare test and unadjusted and adjusted logistic regression analysis.
Factors investigated included: gender, mode of HIV transmission,
time from HIV diagnosis, CD4 count, nation of birth, AIDS, HCVstatus, age, CD8 count, VL, diabetes, smoking, total and HDL cholesterol, eGFR, blood glucose, level of education and employment
and site location. Factors showing unadjusted associations with
a p-value of 10% or smaller, were retained in the multivariable
model.
Results: We identified 183 patients starting EVP and 173 starting the
control regimen from 23 sites. The number of patients starting EVP
included at each site ranged from 1 to 12 and the number of those
starting the control regimen was similar. The most frequently used
drugs in the concurrent group were: TDF (75%), FTC (74%), DRV
(39%), ATV/r (26%), LPV/r (9%), EFV (13%) and RAL (14%). In
univariable analysis, there were differences in median CD4 count
(390 cells/mm3 in EVP versus 348 in controls, p0.002), time from
HIV diagnosis to starting cART (11 versus 3 months, p 0.001) and
prevalence of students (6% versus 3%, p 0.07). No differences
were observed for all other factors examined. The table shows
estimates of the odds ratios (OR) for factors included in the
multivariable model.
Conclusions: CD4 count was higher in EVP-treated patients compared to controls. Guidelines suggest avoiding initiation of EVP in
presence of high VL, possibly explaining this residual difference in
CD4. There was also a tendency to prescribe EVP to people with
perceived lower adherence or hesitant to start or perhaps with a
slow progressing disease.
Abstract P243Table 1. Odds ratios of starting Eviplera from fitting a logistic regression model
Odds ratios of starting eviplera
Characteristic
Unadjusted OR (95% CI)
p-value
Adjusted OR (95% CI)
p-value
CD4 count, cells/mmc (per 100 cells higher)
1.15 (1.03, 1.28)
0.014
1.17 (1.04, 1.32)
0.008
Time from HIV diagnosis to date of starting cART(per year longer)
1.11 (1.03, 1.18)
0.004
1.10 (1.03, 1.18)
0.008
Employment, n (%)
Unemployed
1.00
Employed
1.69 (0.80, 3.55)
0.166
1.00
1.78 (0.79, 4.01)
0.162
Self-Employed
Occasional
1.20 (0.50, 2.84)
1.71 (0.48, 6.11)
0.686
0.408
1.25 (0.50, 3.14)
2.18 (0.58, 8.27)
0.640
0.251
Student
3.23 (0.93, 11.19)
0.065
3.49 (0.93, 13.08)
0.64
Retired/Invalid/Housewife
1.05 (0.28, 3.93)
0.945
0.65 (0.15, 2.71)
0.551
Other/unknown
1.72 (0.80, 3.68)
0.165
1.85 (0.79, 4.31)
0.155
173
P244
Long-term effect of a four-drugs induction regimen for
patients with high baseline viral load
Franco Maggiolo1; Giulia Masini1; Noemi Astuti1; Elisa Di Filippo1;
Simone Benatti1; Daniela Valenti1; Anna Paola Callegaro2 and
Marco Rizzi2
1
Division of Infectious Diseases, AO Papa Giovanni XXIII
BergamoBergamo, Italy. 2Laboratory of Virology and Microbiology,
AO Papa Giovanni XXIII Bergamo, Bergamo, Italy.
Introduction: The long-term effects of an intensified induction
regimen are unknown. In this pilot, randomized, prospective study
we evaluate the effect of a short-term four-drugs induction regimen
in patients with high baseline viral load.
Methods: Naive patients with HIV-RNA 100.000 copies/ml receiving
TDFFTCEFVRAL (group ER) for 4 months and were then
simplified to TDFFTCEFV. Two randomized control groups treated
ab-initio with TDFFTCEFV (E) or TDFFTCRAL (R) were
used.
Results: 19 patients with a mean age of 38 years and mean baseline
CD4 count of 334 (SD 216) cells/mcL and HIV-RNA of 5.47 log (SD 0.32)
copies/mL were enrolled. No baseline significant difference was
observed among groups. Early HIV-RNA reduction was significantly
higher in ER compared to the other groups from week 1 to week 4
(P from 0.026 to 0.003) (figure 1), thereafter HIV-RNA values were
comparable among the groups. At week 96, all patients had an HIVRNA B 50 copies/mL, however only patients in the ER group had in all
cases an HIV-RNA level B 3 copies/mL with a statistically significant
difference compared to E (60%; P 0.038) and R (50%; P0.020). At
96 weeks, CD4 cell median counts were 765 cells/mcL for ER, 600
cells/mcL for E and 771 for R (P0.16), however patients in the ER
group presented a lower proportion of activated CD4CD38
HLADR cells (1.9% versus 3.9 and 3.8%) and CD8CD38HLADR
HLADR cells (10.3% versus 16.8 and 16.5%) and a significantly better
CD4/CD8 ratio (0.98 versus 0.53 and 0.61; P 0.03).
Conclusions: A four-drug regimen in naive patients with high pretherapy viral load improves early virologic response. A quick drop of
HIV-RNA seems to correlate with a sustained virologic response.
Although limited in time (four months), the four-drug regimens correlates with an improved immunological response as measured by the
CD4/CD8 ratio or the percentage of activated CD4 and CD8 cells.
The reasons why this happens deserve further studies. This study
highlights the importance of a personalised therapy especially in high
risk patients.
Poster Abstracts
Reference
1. Maggiolo F, Masini G, Astuti N, Di Filippo E, Benatti S, Valenti D,
et al. Division of Infectious Diseases; Laboratory of Virology and
Microbiology; AO Papa Giovanni XXIII Bergamo, Italy.
P245
Who gets single tablet regimens (STR), and why?
Laura Tarrier and Stephen Kegg
GUM and HIV Medicine, Trafalgar Clinic, Queen Elizabeth Hospital,
London, UK.
Introduction: The BHIVA guidelines now feature three single tablet
regimens (STRs) as recommended treatments for HIV-positive people
new to therapy [1]. They are popular with patients and are attractive
in a number of clinical scenarios. We sought to determine how our
use of STRs had developed over a three-year period, and how the
decision to opt for an STR was made.
Methods: Retrospective case-note review and database interrogation of all patients starting anti-retroviral therapy (ART) from 1st
March 2011 to 31st March 2014.
Results: 215 patients started ART. 58% (125/215) were black-African
and 47% (100/215) were female. Median CD4 at baseline was 272 cells/
mL (range 1-1044 cells/mL). 69 (32%) had a viral load (VL) 100,000
copies/mL. 7 individuals had evidence of transmitted drug resistance.
88 patients started an STR. Two tested positive for HLAB5701. None had
a 10 year CVS risk score of 20% and 36% had a baseline VL
100,000 copies/mL. 127 patients started a non-STR regimen, 29%
had a VL 100 000 copies/mL and none had an elevated CVS risk.
Information regarding baseline renal function and HLAB5701 will be
provided at the conference. The use of STRs increased over the three
years (25% 201112; 57.1% 201213; 44% 201314). There was no
difference in STR prescribing between men and women. In men,
heterosexual male patients were more likely to be prescribed an STR
than MSM males (54% versus 43%, p 0.005). In 43% (38/88) patients
had indicated a preference for an STR and 32/88 expressed a preference
for a particular drug. 2% (2/88) requested to be on the same treatment
as a partner. In those patients who expressed an interest in a particular
drug, four had received information from a friend or partner. In 33%
(29/88) cases an STR was felt by the clinician to be the best option,
largely based on concerns around pill-burden and adherence (31%),
viral load (16%) and renal or cardiac risk (7%).
Abstract P244Figure 1. HIV-RNA reduction among the three groups.
174
Poster Abstracts
Conclusions: Use of STRs is increasing. This is not driven on in our
cohort by cardiovascular risk of HLAB5701 carriage but by patient and
clinician preference, and to a lesser extent by higher baseline viral loads.
Reference
1. British HIV Association (BHIVA). Treatment of HIV-1 positive adults
with antiretroviral therapy. BHIVA. Report, 2013.
P246
Treatment outcome in HIV patients receiving 3- or 4-drug
regimens during PHI
Giulia Maria Bottani1; Maria Letizia Oreni1; Giancarlo Orono2;
Pamela Tau1; Silvia Di Nardo Stuppino1; Elisa Colella1;
Sinibaldo Carosella2; Marta Guastavigna2; Valeria Ghisetti3;
Valeria Micheli4; Massimo Galli1 and Stefano Rusconi1
1
Infectious Diseases Unit, DIBIC Luigi Sacco, Milan, Italy. 2Infectious
Diseases Unit A, Amedeo di Savoia Hospital, Turin, Italy.
3
Microbiology and Virology Laboratory, Amedeo di Savoia Hospital,
Turin, Italy. 4Clinical Microbiology, Virology and Bioemergency, Luigi
Sacco Hospital, Milan, Italy.
Introduction: The optimal timing and modality of therapeutic
intervention during early phases of HIV infection is still debated; in
our prospective observational study we evaluated immunological
and virological outcome in HIV patients treated during acute or
recent HIV infection.
Materials and Methods: A total of 25 naı̈ve patients with acute
(detectable HIV-RNA, immature Western Blot) or recent (documented infection within six months) HIV infection were recruited at the
Infectious Diseases Units of the University of Milan and Turin from
2009 to 2014. Patients received treatment with two NRTIsone
NNRTI/bPI, with or without an induction phase with an additional
fourth drug (raltegravir or maraviroc) until HIV-RNA undetectability
maintained for six months. Blood samples for HIV-RNA, lymphocyte
subsets and tropism assessment were obtained at the beginning
of the treatment (BL). Patients underwent subsequent six-monthly
follow up for clinical outcome, CD4 cell count and HIV-RNA up to 18
months.
Results: Median increase in CD4 cells from 0 to 12 months was
greater in patients treated during acute (n 18) versus recent (n 7)
infection [284/mL, IQR (227456) versus 176/mL, IQR (70235); MannWhitney test, p0.046]. This higher value was maintained through
18 months, although failing to reach statistical significance. Patients
with acute or recent infection did not significantly differ in virological
success (83.3% versus 85.7% at 12 months). We considered CD4 cells
gains at six months (multivariate analysis, ANCOVA; Figure 1) and
detected an inverse correlation with CD4 levels at BL (r 0.517;
p0.008) and a direct correlation with the status of acute infection
(r 0.234, p NS). This last correlation reached statistical significance
at 12 months (r0.418, p0.035), whereas the inverse correlation
with CD4 levels at BL was still present without a statistical
significance (r 0.350; p0.072). Patients treated with three or
four drugs did not show any significant difference in immunological
nor virological response (Mann-Whitney and x2 test). Modification or
interruption of therapy for tolerability took place in 4 out of 25
patients, all while receiving four drugs; two patients underwent STI
between 12 and 18 months following virological success.
Conclusions: Treatment of primary infection appeared to be effective
in preserving the pool of CD4 cells in acute more than recent
infection. There was no evidence of a different outcome through the
addition of a fourth drug to the standard treatment.
¸
Abstract P246Figure 1. CD4/cL recovery among BL and months 6
and 12.
P247
An indirect comparison of efficacy and safety of
elvitegravir/cobicistat/emtricitabine/tenofovir and
dolutegravir abacavir/lamivudine
Felipe Rogatto1; Stephane Bouee2; Vivianne Jeanbat2;
David Piontkowsky3; Filipa Aragao1 and Matthew Bosse3
1
Medical Affairs, Gilead Sciences Europe, Uxbridge, UK.
2
Pharmacoepidemiology, CEMKA, Bourg La Reine, France.
3
Medical Affairs, Gilead Sciences, Foster City, CA, USA.
Background: Integrase strand transfer inhibitors (INSTI) are the
standard of care for naı̈ve HIV-infected individuals due to their
favourable efficacy and safety profile. The newest INSTIs, elvitegravir
and dolutegravir, have not been evaluated in a head to head study;
however, both have been compared to efavirenz/emtricitabine/
tenofovir (EFV/FTC/TDF) in phase III trials. Elvitegravir/cobicistat/
emtricitabine/tenofovir DF (E/C/F/TDF) was compared to EFV/FTC/
TDF for 144 weeks in Gilead Study 102 (GS-102), while dolutegravir
(DTG) with the abacavir/lamivudine fixed-dose combination (ABC/
3TC) was compared to EFV/FTC/TDF for 96 weeks in the SINGLE
study. The objective of this analysis is to perform an indirect
comparison at 48 and 96 weeks of E/C/F/TDF to DTGABC/3TC by
using the two trials evaluating each of these regimens compared to
EFV/FTC/TDF.
Methods: An indirect comparison was performed by using Bucher’s
methodology to calculate risk differences based on the two phase III
clinical trials described above.
Results: At week 48 (snapshot analysis), 88% of the patients on E/C/F/
TDF and DTGABC/3TC had HIV RNA B50 c/mL, while 84% and 81%
of patients on EFV/FTC/TDF were suppressed in GS-102 and SINGLE,
respectively. At week 96, 84% of patients receiving E/C/F/TDF
compared with 80% of patients receiving DTGABC/3TC remained
175
Poster Abstracts
suppressed, while 82% and 72% on EFV/FTC/TDF maintained HIV RNA
B50 c/mL in GS-102 and SINGLE. At week 144 80% of patients on E/C/
F/TDF remained suppressed (vs. 75% of the patients on EFV/FTC/TDF).
Results of indirect comparison showed a risk difference of HIV RNA
B50 copies per mL between E/C/F/TDF compared with DTGABC/
3TC of 4% (CI 95%11 to 3) for the ITT 48 weeks (p 0.3) and
5% (95% CI 13 to 3) for the ITT 96 weeks (p 0.2). In regards to
safety, there was no significant difference between E/C/F/TDF and
DTGABC/3TC for any adverse event (AE) (p 0.3), serious AEs
(0.13), drug related AEs (0.7), or drug-related serious AEs (0.6).
Conclusions: In GS-102 and SINGLE, 88% of the patients on E/C/F/
TDF and DTGABC/3TC were virologically suppressed at week 48. At
week 96, these proportions were 84% for E/C/F/TDF and 80% for
DTGABC/3TC. The indirect efficacy comparisons between EVG/
COBI/FTC/TDF and DTGABC/3TC at week 48 and 96 revealed no
statistically significant differences.
6.6% in MT), RAL in 6.2% (2% in VF, 10.5% in MT). Median duration on
ETR was 3.7 and 2.2 years in the VF and MT group, respectively. In the
VF group, HIV RNA was B50 c/ml in 71.7% (71.1% without bPI, 72%
with bPI) of the patients at M12, 72.8% (71% without bPI, 73.3% with
bPI) of the patients at M24. In the MT group, HIV RNA wasB50 c/ml in
90.5% of the patients at M12 and 93.1% at M24. ETR was discontinued
in 8.8% of the patients (12.8% in VF, 5.4% in MT) for adverse events in
23.9% of cases (21.5% in VF, 29.5% in MT), treatment failure in 15.2%
(16.2% in VF, 7.4% in MT) or simplification in 5.4% (4.6% in VF, 7.4% in
MT). In the VF group, factors associated with virologic failure in
multivariate analysis were a longer duration of HIV infection (OR 2.6;
95% CI 1.74.0) and baseline HIV RNA 5 log10 c/ml (OR: 2.0; 95% CI
1.33.2) but not the association with a bPI.
Conclusion: This large study shows that in ARV-pre-treated patients
ETR is well tolerated with a high efficacy when combined with other
active drugs, even when the regimen does not include a bPI.
TREATMENT STRATEGIES EXPERIENCED
PATIENTS
P248
Efficacy and tolerability of Etravirine in HIV-1 adult patients:
Results of a large French prospective cohort
Clotilde Allavena1; Christine Katlama2; Laurent Cotte3; PierreMarie Roger4; Pierre Delobel5; Antoine Cheret6; Claudine Duvivier7;
Isabelle Poizot-Martin8; Bruno Hoen9; Andre Cabié10;
Arnaud Cheret11; Rima Lahoulou11; Francois Raf1 and
Pascal Pugliese4
1
Infectious Diseases, CHU Hôtel Dieu, Nantes, France. 2Infectious
Diseases, AP-HP Hôpital Pitié Salpétrière, Paris, France. 3Infectious
Diseases, Hospices Civils de Lyon, Lyon, France. 4Infectious Diseases,
CHU Archet Universite Nice Sophia Antipolis, Nice, France.
5
Infectious Diseases, CHU de Purpan, Toulouse, France. 6Infectious
Diseases, CHU Druon, Tourcoing, France. 7Infectious Diseases, IHU
Imagine, Necker Hospital Descartes University, Paris, France.
8
Infectious Diseases, AP-HM Hôpital Sainte Marguerite, Marseille,
France. 9Infectious Diseases, CHU Besançon, Besançon, France.
10
Infectious Diseases, CHU Fort de France, Fort de France, France.
11
Janssen, Issy Les Moulineaux, France.
Background: Etravirine (ETR) was approved in France in Sept 2008, to
be used in combination with a ritonavir-boosted protease inhibitor
(bPI) and others antiretrovirals (ARV) in HIV-infected pre-treated
patients.
Objectives: To describe in a real life setting efficacy and tolerability of
ETR-including regimen and factors associated with virologic response.
Method: In the French DatAIDS cohort including 18,647 patients, we
selected patients who initiated an ETR-including regimen between September 2008 and July 2013. Demographic data and clinico-biological
data were collected from the standardized electronic medical record
Nadis† . Analyses were done in patients starting ETR and sub-analyses
were performed in pre-treated patients starting ETR for virologic
failure (VF) or maintenance (MT) therapy, with or without bPI.
Results: 2083 patients (ARV-naı̈ve n77, VF n 1014, MT n992)
were included: median age 47 years, 73.3% male, median duration of
HIV infection 15.7 years, CDC stage C 38.7%, HBV/HCV co-infection
25.7%. In pre-treated patients, 75.5% previously received NNRTIs
(median duration on EFV and NVP of 480 and 396 days, respectively),
94.3% bPIs, 30.8% raltegravir (RAL) and 19.4% enfuvirtide. The most
frequent ARVs associated with ETR were two NRTIs in 37.2% of the
cases (21.9% in VF, 52.9% in MT), 1 bPIRAL in 10.1% (13.5% in VF,
P249
Impact of etravirine use on hospitalization rates among
highly pre-treated failing HIV-1 infected individuals between
2005 and 2011
Jean-Marc Lacombe1; Cecile Goujard2; Marc-Antoine Valantin3;
Arnaud Cheret4; Rima Lahoulou4; Pierre-Marie Girard5 and
Dominique Costagliola1
1
INSERM and Sorbonne Universités, UPMC Univ Paris 06, Pierre Louis
Institute, Paris, France. 2AP-HP, Hôpital Bicêtre, Service de médecine
Interne, Le Kremlin Bicêtre, France. 3AP-HP, Hôpital Pitié Salpétrière,
Service de Maladies infectieuses et tropicales, Paris, France.
4
JANSSEN, Issy-les-Moulineaux, France. 5AP-HP, Hôpital
Saint-Antoine, Service des maladies infectieuses et tropicales,
Paris, France.
Introduction: Etravirine (ETR), a non-nucleoside reverse transcriptase
inhibitor available in France since 2006, is indicated for the
treatment of HIV-1 infection in combination with a ritonavir boosted
protease inhibitor (PI) in antiretroviral treatment-experienced adult
patients. To assess its impact in routine clinical care, our objective
was to compare hospitalization rates in highly pre-treated failing
HIV-1 infected individuals between 2005 and 2011 depending on
whether or not they received ETRPI.
Methods: From the French Hospital Database on HIV (ANRS CO4), we
selected highly pre-treated individuals (prior exposure to at least
2NRTI, 2PI and 1 NNRTI) with a viral load (VL)50 copies/mL
initiating a new regimen between 2005 and 2011. Hospitalization
rates were calculated for each calendar month and depending on
whether patients never received ETRPI at any time or during
months before initiating ETRPI (no ETRPI) or during months
after initiating ETRPI (ETRPI), using an intention to continue
treatment approach. Poisson regression models were used to
compare incidence between the two groups, after adjustment for
potential confounders (age, transmission group, origin, AIDS, PCP
prophylaxis, viral load, CD4, nb of previous ARV).
Results: Overall 3884 patients fulfilled inclusion criteria. Among
them 838 (21.6%) received ETRPI at least once. Among all enrolled
patients, 35.8% had CD4 B200/mm3, 17.5% had VL 100,000
copies/ml, 42.8% had had an AIDS event and 47.8% had received
more than 10 different antiretroviral drugs. There were 2484
hospitalizations in 808 individuals over 13,986 patient-years. The
hospitalization rates for 1000 P-Y were 169.0 for the ETRPI group
and 179.3 for the no ETRPI group. After adjustment, the
corresponding figures were 144.8 for 1000 P-Y and 192.7 for 1000
P-Y respectively, with a relative risk estimated as 0.75 (95% CI 0.67
0.84).
176
Poster Abstracts
Conclusions: Access to ETRPI between 2005 and 2011 was
associated with a 25% reduction in the hospitalization rate among
highly pre-treated failing HIV-1 infected individuals.
Abstract P250Table 1. Probability of virological failure in
experienced patients treated with DRV/r-based Dual Therapy
HR
P250
IC 95%
IC 95%
Lower
Upper
p value
Male Gender
0.905
0.497
1.648
0.745
Gaetana Sterrantino ; Mauro Zaccarelli ; Antonio Di Biagio ;
Andrea Rosi4; Bianca Bruzzone3; Paola Cicconi5; Tiziana Carli6;
Maria Luisa Biondi7; Andrea Antinori8; Dario Bartolozzi1 and
Giovanni Penco9
1
Malattie Infettive e Tropicali, Azienda Ospedaliera Universitaria
Careggi, Florence, Italy. 2Unità Operativa Immunodeficienze Virali,
INMI L. Spallanzani IRCCS, Rome, Italy. 3Malattie Infettive e Tropicali,
Azienda Ospedaliera Universitaria San Martino, Genoa, Italy.
4
Dipartimento di biotecnologie mediche, Università di Siena, Siena,
Italy. 5Malattie Infettive e Tropicali, Azienda Ospedaliera San Paolo,
Milan, Italy. 6Malattie Infettive e Tropicali, Ospedale Misericordia,
Grosseto, Italy. 7Diagnostica Molecolare Infettivologica, Azienda
Ospedaliera San Paolo, Milan, Italy. 8Dipartimento Clinico, INMI L.
Spallanzani IRCCS, Rome, Italy. 9Malattie Infettive, Ente Ospedaliero
Ospedali Galliera, Genoa, Italy.
Age (per year)
IDU
1.021
0.759
0.994
0.429
1.049
1.343
0.127
0.343
Non Italian
1.390
0.485
3.983
0.540
HIV non-subtype vs B
1.979
0.858
4.561
0.109
HCV positivity
1.070
0.981
1.168
0.128
Background: We assessed the virological response of DRV/r-based
dual therapy in drug-experienced patients included in the Italian
antiretroviral resistance database (ARCA).
Material and Methods: Patients included in the study were treated
with DRV/r in association with raltegravir (RAL), etravirine (ETV) or
maraviroc (MAR) following treatment failure(s) and with a resistance
test and at least one follow-up visit available. Observation was
censored at last visit under dual therapy and survival analysis and
proportional hazard models were used, taking virological failure
(confirmed 50 c/mL HIV-RNA) as the end-point.
Results: Of the total 221 patients included, 149 (67.4%) started DRV/
r with RAL, 45 (20.4%) with ETV, 27 (12.2%) with MAR. Patients
characteristics at the start of dual regimen were as follows: mean
number of previous regimens, nine (IQR: 513); non-B subtype, 17
(7.7%); median CD4 count, 347 (IQR: 246544); undetectable viral
load, 74 (33.5%). Full DRV/r resistance was detected in one (0.5%,
HIV-DB interpretation system), 13 (5.9%, ANRS) and 17 patients
(7.7%, Rega). 69 virological failures (31.2%) were observed during
follow-up. At survival analysis, the overall proportion of failure was
29.2% at one year and 33.8% at two years. The proportion of failure
was lower in patients starting with undetectable versus detectable
viral load (13.3% and 25.2% versus 37.4% and 38.8% at one and two
years, respectively, p0.001 for both analyses) and in patients
treated with DRV 600 BID versus 800 QD (HR: 0, 56; 95% CI 0.31
0.99; pB0.05). By regimen, patients treated with DRV/r-RAL showed
a non-significant lower proportion of failure (27.7% at one year,
32.0% at two years) if compared with DRV/r-MAR (35.9%, 47.1%) and
DRV/r-ETV (34.1%, 34.1% at one and two years). In the adjusted
proportional model, no significant difference among the three
regimens was detected. A significant lower risk of failure was
associated with higher overall GSS (HIV-DB HR: 0.53, 95% CI 0.32
0.88, p 0.014; Rega 0.60, 0.40-0.88, pB0.01; ANRS 0.55, 0.34
0.90, p0.017), while a higher risk of failure was associated with
detectable HIV-RNA (3.02, 1.705.72, pB0.001).
Conclusions: Among experienced patients, the best candidates to
dual-therapy regimens including DRV/r are those with undetectable
viral load and higher GSS. The association with RAL is the most
commonly used but no clear advantage with respect to ETV or
MAR was observed in our dataset, possibly due to the limited
sample size.
Darunavir-based dual therapy in HIV experienced patients
1
2
3
N Previous Regimens
0.993
0.897
1.100
0.890
N PI used
1.062
0.928
1.214
0.382
Und VL at Dual switch
3.022
1.696
5.720
B0.001
Baseline CD4
CD4 nadir
0.973
1.032
0.920
0.900
1.030
1.183
0.348
0.653
Raltegravir
1
MAR (vs RAL)
1.372
0.673
2.797
0.385
ETV (vs RAL)
1.157
0.473
2.831
0.750
DRV 600 bid (vs 800 QD)
0.556
0.314
0.986
B0.05
GSS (REGA, each point)
0.595
0.400
0.884
B0.01
P251
Week 48 results of a Phase IV trial of etravirine with
antiretrovirals other than darunavir/ritonavir in
HIV-1-infected treatment-experienced adults
Eduardo Arathoon1; Asad Bhorat2; Rodica Silaghi3; Herta Crauwels4;
Ludo Lavreys4; Lotke Tambuyzer4; Simon Vanveggel4 and
Magda Opsomer4
1
Clinica Familiar Luis Angel Garcia, Guatemala City, Guatemala.
2
Soweto Clinical Trials Centre, Johannesburg, South Africa.
3
Infectious Diseases Hospital, Brasov, Romania. 4Janssen Infectious
Diseases BVBA, Beerse, Belgium.
Introduction: In DUET, etravirine (ETR) 200 mg bid had durable
efficacy and a favourable safety profile versus placebo, both arms
with an optimised background regimen (BR) including darunavir/
ritonavir (DRV/r). TMC125IFD3002 (VIOLIN; NCT01422330) investigated ETR plus ARVs other than DRV/r.
Materials and Methods: This was a 48 week, Phase IV, open-label,
single-arm, multicentre study. HIV-1-infected treatment-experienced
adult patients on 8 weeks ARV therapy prior to screening, switching
either for virologic failure (VF) (viral load [VL] 500 c/mL) or regimen
simplification/AEs (RS/AE) (VLB50 c/mL), received active ETR 200 mg
bid with an investigator-selected BR of 1 active ARVs, but excluding
DRV/r or NRTIs only. The primary objective was to evaluate safety,
tolerability and pharmacokinetics (PK).
Results: Of 211 treated patients, 55% were female, 61% black/
African American. 155 patients (73%) had baseline (BL) VL 50 c/mL
versus 56 (27%) with BL VL B50 c/mL. Between these two latter
subgroups, median BL VL was 4.42 versus 1.28 log10 c/mL and CD4
count 238 versus 410.5 cells/mm3. Overall, 96% previously used B2
NNRTIs and 99% used5 PIs; median number of BL NNRTI RAMs
was 2, PI RAMs 5 and NRTI RAMs 1. Overall, most common BR ARVs
were PIs (83%), mostly lopinavir/r (62%) and mostly used alone
(20%) or with 1 or 2 NRTIs (61%). Raltegravir was used in 9% of
patients. Most frequent AEs (any cause/grade) were diarrhoea (17%)
and URTI (8%). Incidence of grade 34 AEs was 13%, serious AEs 5%
(no rashes; none ETR related), AEs leading to discontinuation 4%, AEs
177
possibly related to ETR 23% and AEs of interest: rash (any type) 4%,
hepatic 6% and neuropsychiatric 3%. At week 48, VF and RS/AE
virologic responses (% patients with VL B50 c/mL; FDA Snapshot)
were: 48% (74/155) and 75% (42/56), respectively. VF rates were
42% and 13%; 10% and 13% had no VL data in the week 48 window.
The percentage of patients adherent to treatment (assessed based
on PK sampling plus ETR pill count) was 47% (69/148) and 57% (30/
53), in VF and RS/AE, respectively. Median CD4 count (NCF)
increases were 0.0 and 24.0 cells/mm3. In 29/49 of VFs with
genotypic data at failure, ETR RAMs emerging in 5 patients were
Y181C, E138A and M230L. The geometric mean ETR AUC12h was 4877
ng.h/mL and C0h 293 ng/mL (N 199).
Conclusions: Results of this study were consistent with those for ETR
in other similar populations and support the use of ETR 200 mg bid
with a non-DRV/r based BR.
P252
Gag drug resistance mutations in HIV-1 subtype C patients,
failing a protease inhibitor inclusive treatment regimen,
with detectable lopinavir levels
Sameshnee Kelly Pillay; Urisha Singh; Avashna Singh;
Michelle Gordon and Thumbi Ndungu
HIV Pathogenesis Programme, University of Kwa-Zulu Natal, Durban,
South Africa.
The development of antiretroviral (ARV) drugs and their use in
human immunodeficiency virus type 1 (HIV-1) has led to the effective
control of HIV replication in infected patients. However the emergence of resistant HIV-1 strains still remains a problem. Literature has
shown that mutations may accumulate in the protease (PR) and gag
regions of HIV-1 patients who fail therapy with protease inhibitor
(PI) drugs [1,2]. Gag mutations have also been found to play an
important role in the evolution of PI resistance [2]. Despite this, the
standard genotypic drug-resistance test examines mutations in the
reverse transcriptase (RT) and PR region of HIV-1 and not gag [3].
This study investigated the frequency of gag drug resistance mutations in the absence of major PI mutations in HIV-1 subtype C
patients, failing a PI inclusive treatment regimen. Sixty-eight samples
were retrieved from patients that were classified as second line treatment failures as they had a viral load greater than 1000 copies\mL, as
well as detectable lopinavir (LPV) levels. The gag and protease region
of these patients were genotyped. Mutations in the gag and protease
region were assessed using the REga Db sequencing tool and the CPR
programme on the Stanford University HIV drug resistance database.
The mean LPV level of these samples was 11.66 mg/mL. 69.11%
(n 46) of the patients have no major PI mutations in protease. The
following mutations that are associated with PI exposure were
present in the data set: G62R (n6), H219Q (n 11), S737T (n 8),
I389T (n 8) and Q474L (n 7). Predictably, mutations that are
associated with PI resistance were found, which are generally located
in the p7/p1 and p1/p6 cleavage site. These mutations are K436R
(n 4), I437V (n1), L449P (n5), R452K (n 4) and P453L\T
(n 9). These results contribute to the knowledge of resistance
mutations in gag and their impact on PI resistance.
References
1. Fun A, Wensing AM, Verheyen J, Nijhuis M. Human immunodeficiency virus gag and protease: partners in resistance. Retrovirology.
2012;9:63.
2. Dam E, Quercia R, Glass B, Descamps D, Launay O, Duval X, et al.
Gag mutations strongly contribute to HIV-1 resistance to protease
inhibitors in highly drug-experienced patients besides compensating
for fitness loss. PLoS Pathogens. 2009;5(3):e1000345.
Poster Abstracts
3. Panel on Antiretroviral Guidelines for Adults and Adolescents.
Guidelines for the use of antiretroviral agents in HIV-1-infected
adults and adolescents. Department of Health and Human Services [cited 2014 July 11]. Available from: http://aidsinfo.nih.gov/
ContentFiles/AdultandAdolescentGL.pdf
P253
Antiretroviral therapy (ART) management of Low-Level
Viremia in Taiwan (ALLEVIATE)
Chien-Yu Cheng1; Yu-Zhen Luo2,3; Pei-Ying Wu2,3; Wen-Chun Liu2,3;
Shan-Ping Yang2,3; Jun-Yu Zhang2,3; Shu-Hsing Cheng1 and
Chien-Ching Hung2,3
1
Department of Infectious Diseases, Taoyuan General Hospital,
Tao-Yuan, Taiwan. 2Department of Infectious Diseases, National
Taiwan University Hospital, Taipei, Taiwan. 3Department of Infectious
Diseases, National Taiwan University College of Medicine, Taipei,
Taiwan.
Introduction: This retrospective study aimed to investigate that if
switch of combination antiretroviral therapy (cART) would result in
viral suppression (B40 copies/mL) at 48 weeks for patients with
persistent low-level viremia after having received cART for six
months or more at two hospitals designated for HIV care in Taiwan.
Materials and Methods: Between January 2001 and January 2013,
patients were enrolled if plasma HIV RNA load (PVL) were 20 to
B1000 copies/mL detected for six months or more [1,2]. Using a
standardized data collection form, we recorded data of PVL and CD4
count before cART and at the detection of low-level viremia,
serologies for hepatitis B and C virus, risk factors, duration of cART
exposure, years of HIV diagnosed and ever experiencing treatment
failure. The strategy of switch is based on the clinical guidelines of
BHIVA, which suggest change of cART from non-nucleoside reversetranscriptase inhibitors (nNRTIs) or unboosted protease inhibitor (PI)
to boosted PI, newer boosted PI or ARV of different mechanism [3].
Results: In this study, 165 patients were enrolled, 119 patients
(72.1%) did not switch (Group 1), and 46 patients (27.9%) switched
previous regimens to ARV of different mechanism (Group 2). The two
groups differed significantly in the proportion of injecting drug users
(IDU) (Group 1 vs Group 2, 10.9 vs 26.1%) and median PVL (67 vs 159
copies/mL), and the proportion of PVL B200 copies/mL (84.0% vs
58.7%) when low-level viremia was first detected. In Group 1, 39
(32.8%) continued two nucleoside reverse-transcriptase inhibitors
(NRTIs) plus nNRTI; 29 (24.4%) 2 NRTIs plus PI, 47 (39.5%) 2 NRTIs
plus boosted PI, and 4 (3.3%) 2 NRTIs plus integrase inhibitor (II). In
Group 2, two (4.3%) switched to 2 NRTIs plus PI, 38 (82.6%) 2 NRTIs
plus boosted PI, three (6.5%) 2 NRTIs plus II and three (6.5%) boosted
PI plus II. In multivariate analysis, IDUs (adjusted odds ratio [AOR],
6.757; 95% CI 2.42718.868) and PVL of 200999 copies/mL at
enrollment (AOR, 4.902; 95% CI 1.99212.048) were more likely to
be switched. At 48 weeks, patients in Group 2 were more likely to
achieve PVL B40 copies/mL than Group 1 (82.6% vs 63.0%, p
0.016), while no difference was observed in achieving PVL B200
copies/mL between the two groups (95.7% vs 92.4%, p0.729).
Conclusions: According to the clinical guidelines of BHIVA, patients
with low-level viremia who switched to cART consisting of 2 NRTIs
plus boosted PI or newer mechanisms were more likely to reestablish viral suppression to B40 copies/mL at week 48.
References
1. Laprise C, de Pokomandy A, Baril JG, Dufresne S, Trottier H.
Virologic failure following persistent low-level viremia in a cohort of
HIV-positive patients: results from 12 years of observation. Clin Infect
Dis. 2013;57(10):148996.
2. Easterbrook PJ, Ives N, Waters A, Mullen J, O’Shea S, Peters B,
et al. The natural history and clinical significance of intermittent
178
Poster Abstracts
Abstract P253Table 1. Characteristics of patients with persistent low level viremia
Age9SD (y/o)
Total
No switch
Switch of
(n165)
of cART (n119)
cART (n46)
p
0.096
39911
38911
41910
Male (%)
158 (95.8%)
114 (95.8%)
44 (95.7%)
0.967
MSM (%)
122 (73.9%)
91 (76.5%)
31 (67.4%)
0.242
IDU (%)
25 (15.2%)
13 (10.9%)
12 (26.1%)
0.027
HBV (%)
19 (11.5%)
14 (11.8%)
3 (6.5%)
0.810
28 (17.0%)
184 (1928)
17 (14.3%)
187 (1707)
9 (19.6%)
171 (10928)
0.330
0.937
HCV (%)
Before cART CD4, median (range), cells/uL
5.29
5.29
5.29
0.312
98 (59.4%)
73 (61.3%)
25 (54.3%)
0.480
422 (631092)
419 (631092)
431 (1341010)
0.156
PVL at enrollment, copies/mL
83 (21999)
67 (21939)
159 (21999)
0.002
PVL of 20199 (%)
127 (77.0%)
100 (84.0%)
27 (58.7%)
0.001
PVL of 200999 (%)
38 (23.0%)
19 (16.0%)
19 (41.3%)
0.001
47 (12391)
4 (114)
44 (15321)
4 (114)
58 (12391)
4 (213)
0.062
0.356
42/165
26/119
16/46
0.111
2NRTIsnNRTI
39 (23.6%)
39 (32.8%)
0 (0%)
B0.001
2NRTIsPI
31 (18.8%)
29 (24.4%)
2 (4.3%)
0.003
2NRTIsPI/r
85 (51.5%)
47 (39.5%)
38 (82.6%)
B0.001
2NRTIsII
7 (4.2%)
4 (3.3%)
3 (6.5%)
0.967
IIPI/r
3 (1.8%)
0 (0%)
3 (6.5%)
0.021
Before cART PVL, median, copies/mL, log10
PVL5 log10 (%)
CD4 at LLV, median (range), cells/uL
Duration of cART exposure, median (range), weeks
Years of HIV diagnosed, median, (range), years
Ever treatment failure (%)
Current cART
viraemia in patients with initial viral suppression to B400 copies/ml.
AIDS. 2002;16:15217.
3. Lohse N, Kronborg G, Gerstoft J, Larsen CS, Pedersen G, Pedersen
C, et al. Virological control during the first 618 months after
initiating highly active antiretroviral therapy as a predictor for
outcome in HIV-infected patients: a Danish, population-based, 6year follow-up study. Clin Infect Dis. 2006;42:13644.
P254
Effectiveness and durability of darunavir/ritonavir (DRV/r)
in DRV/r-experienced HIV-1-infected patients in routine
clinical practice
Andrea Antinori1; Massimo Galli2; Nicola Gianotti3; Cristina Mussini4;
Tiziana Quirino5; Katia Sterrantino6; Daniela Mancusi7 and
Roberta Termini7
1
Clinical Department, National Institute for Infectious Diseases L.
Spallanzani, Rome, Italy. 2Department of Infectious Disease, L. Sacco
University Hospital, Milan, Italy. 3Clinic of Infectious Diseases, San
Raffaele Hospital, Milan, Italy. 4Institute of Infectious Diseases,
University of Modena and Reggio Emilia, Modena, Italy. 5Unit of
Infectious Diseases, Busto Arsizio Hospital, Busto Arsizio, Italy.
6
Division of Tropical and Infectious Diseases, Careggi Hospital,
Florence, Italy. 7Medical Affairs, Janssen SpA, Cologno Monzese, Italy.
Introduction: This was a descriptive non-interventional study in HIV1-infected patients treated with DRV/r conducted in the clinical
setting, with a single-arm prospective design. The primary objective
was to collect data on utilization of darunavir/ritonavir (DRV/r) under
the conditions described in the marketing authorization. Efficacy
(measured as viral load [VL] B50 copies/mL and CD4 cell count)
was evaluated for DRV/r in combination with other antiretroviral
(ARV) agents in routine clinical practice in Italy.
Materials and Methods: Here we describe an analysis of effectiveness and durability data from two cohorts of DRV/r-experienced
patients with HIV-1 infection, already receiving DRV/r according to
usual clinical practice, collected prospectively from June 2009 to
December 2012: Cohort 1, data from patients from the DRV/r Early
Access Program (TMC114-C226 study; N235 patients) and Cohort
2, a separate cohort of ARV-DRV/r-experienced patients (N 407
patients), treated with DRV/r in the market. Patient characteristics
are shown in Table 1.
Results: The median length of DRV/r exposure during the study was
925 days (interquartile range [IQR] 6921006) in Cohort 1, and 581
(IQR 508734) days in Cohort 2. Of those patients that completed
the study, 94% and 87% of patients were virologically suppressed in
Cohort 1 and 2, respectively, at last study visit (LSV). As expected, the
virological suppression rate was higher in patients with baseline VL
B50 copies/mL (Table 2). Mean CD4 cell counts improved from
baseline to LSV in both cohorts (Cohort 1: 54 cells/mL [95% CI 31,
77] and Cohort 2: 59 cells/mL [95% CI 44, 73]). High persistence
rates were seen in both cohorts, with 75.3% of patients in Cohort
1 and 82.6% in Cohort 2 remaining on treatment at LSV; very
few patients discontinued due to virologic failure (Table 1). Other
reasons for study discontinuation are shown in Table1. Very few
patients changed DRV/r dosing during the study, 15 from 1200 to 800
mg o.d.
Conclusions: In patients already treated with DRV/r, DRV/r-based
ARV treatment provided effective viral suppression with long-lasting
durability, low virological response failure, low discontinuation rates
and good tolerability. These data confirm DRV/r to be an effective
treatment choice in previously treated patients.
179
Poster Abstracts
Cohort 1 (N 235) N, (%)
Parameters
Cohort 2 (N 407) N, (%)
Age, yrs, mean9SD
49.397.1
46.699.4
Female, n (%)
45 (19.1)
107 (26.3)
VL (HIV-RNA) B50 copies/mL, n (%)a at study enrolment
192 (85)
298 (74.9)
7 (3.1)
25 (6.2)
01 year
110 years
0
6 (2.6)
53 (13.0)
82 (20.1)
1015 years
62 (26.4)
66 (16.2)
1520 years
89 (37.9)
85 (20.9)
20 years
76 (32.3)
110 (27.0)
2 (0.9)
11 (2.7)
A
30 (12.8)
139 (34.2)
B
C
80 (34.0)
125 (53.2)
121 (29.7)
147 (36.1)
Time since first DRV dose (days), at study enrolment mean9SD
12429208
5019402
Study Duration, days mean9SD
8129286
5839188
CD4 B100 cells/mL, n (%)b at study enrolment
Duration of HIV infection, n (%)
NA
CDC clinical stage, n (%)
DRV dose at study entry, mg/day, n (%)
1200
232
262
800
3
145
a
VL data only available in 226 Cohort 1 and 398 Cohort 2 patients. bCD4 data only available in 226 Cohort 1 and 403 Cohort 2 patients.
Virological Efficacy
Cohort 1 (N 235) N, (%)
Cohort 2 (N 407) N, (%)
All
203 (88.6)
331 (83.6)
BL VL B50 copies/mL
177 (94.1)
263 (89.2)
BL VL ]50 copies/mL
19 (59.4)
60 (65.2)
No values for BL VL
7 (77.8)
8 (88.9)
Total discontinuations at LSV, n (%)
Reasons for discontinuation, n (%)
56 (24.7)
71 (17.4)
Insufficient virological response
8 (3.4)
4 (1.0)
Death
10 (4.3)
9 (2.2)
Study emergent adverse event
3 (1.3)
9 (2.2)
Parameters
LSV VL [HIV-RNA B50 copies/mL], n (%)a
Other study emergent medical reason
0
1 (0.2)
Lack of compliance
4 (1.7)
8 (2.0)
Lost to follow-up
23 (9.8)
18 (4.4)
Other
9 (3.8)
20 (4.9)
a
VL data only available in 226 Cohort 1 and 398 Cohort 2 patients.
P255
Efficacy of a dual therapy based on darunavir/ritonavir and
etravirine in ART-experienced patients
Jose Ignacio Bernardino1; Francisco Xavier Zamora1; Eulalia Valencia2;
Victoria Moreno2; Jorge Vergas3; Maria Jesus Tellez3;
Vicente Estrada3 and Juan Gonzalez-Garcia1
1
HIV Unit, Internal Medicine, Hospital La Paz, IdiPAZ, Madrid, Spain.
Servicio Enfermedades Infecciosas, Hospital Carlos III, Madrid, Spain.
3
nfectious Diseases Unit, Internal Medicine, Hospital Clinico
Universitario, Madrid, Spain.
2
Introduction: Nucleoside reverse transcriptase inhibitors (NRTI)sparing regimens have been studied in antiretroviral therapy
180
(ART)-naı̈ve patients but data with ART-experienced are scarce. NRTIsparing regimens may be an option in patients with toxicities and for
simplification reasons.
Methods: Retrospective multicentre analysis including ART-experienced
patients starting treatment with darunavir/ritonavir and etravirine
(DRV/r 800 mg/100 mg QD or 600 mg/100 mg BID and ETV 400 mg QD
or 200 mg BID) with at least six months of follow-up. Primary endpoint
was proportion of patients with VL B50 copies/mL at 48 weeks with
an ITT analysis (missing or switch equals failure). Secondary endpoints
were safety, CD4 count and lipid changes over 48 weeks.
Results: Seventy-five patients were included of whom 44 (58.6%)
had HIV RNA B50 copies/mL. Baseline characteristics: median age 50
years (IQR 3465), 72% males, 93% Caucasians, 38.6% hepatitis C,
and 45.4% with CDC C stage. Median HIV duration and time on ART
were 20 (IQR 728) and 14 years (IQR 521) respectively. Reasons
for switching were virologic failure in 27 (36%), simplification in 25
(33.3%), toxicity in 20 (26.6%) and other 3 (4.1%). Most of them
received DRV/r and ETV QD. Thirty-nine patients had NNRTI
resistance mutations [28 K103N (37.3%), 6 Y181I/C (8%), 3 G190A
(4%)] and 29 patients had ]1 primary PI mutations. Main analysis
(ITT) showed that 67 (89.3%) had a VL undetectable at 24 weeks
(95% CI 83.195.5) and 57 (76%) at 48 weeks (95% CI 68.483.6). On
treatment analysis showed that 94.3% and 89% had a viral load B50
copies at 24 and 48 weeks, respectively. 11 (14.6%) patients
discontinued the regimen (three virologic failures, three switching
to darunavir/ritonavir monotherapy, two to salvage regimen and
three due to toxicity). No significant changes in CD4 count and
lipid changes were observed at 48 weeks.
Conclusions: Dual therapy with Darunavir/ritonavir and etravirine is
an efficacious and safety option in ART-experienced HIV patients
even in patients on virologic failure.
TREATMENT STRATEGIES SWITCH
STUDIES
P256
Efficacy of PI monotherapy versus triple therapy for 1964
patients in 10 randomised trials
Jose Arribas1; Pierre-Marie Girard2; Nicholas Paton3; Alan Winston4;
Anne-Genevieve Marcelin5; Daniel Elbirt6; Andrew Hill7 and
Maria Blanca Hadacek8
1
IdiPAZ, Hospital la Paz, Madrid, Spain. 2Maladies Infectieuses et
Tropicales, Hopital Saint-Antoine, Paris, France. 3Clinical Trials Unit,
Medical Research Council, London, UK. 4Jefferies Research Wing, St
Mary’s Hospital, London, UK. 5Virology, Hopital Pitie Salpetriere,
Paris, France. 6AIDS Centre, Kaplan Medical Centre, Rehovot, Israel.
7
Pharmacology and Therapeutics, University of Liverpool, Liverpool,
UK. 8EMEA, Janssen, Issy-les-Moulineux, France.
Introduction: The efficacy of protease inhibitor monotherapy has
been analyzed with different endpoints: initial HIV-1 RNA rebound,
long-term HIV-1 RNA suppression after re-intensification, treatmentemergent drug resistance, neurocognitive testing and HIV-1 RNA in
the cerebrospinal fluid (CSF).
Methods: A PUBMED search identified nine randomised trials of PI
monotherapy versus triple therapy in patients with HIV RNA B50
copies/mL at baseline. Results from the recently completed PROTEA
trial were also included. The percentage of patients with HIV RNA
suppression B50 copies/mL was analyzed using switch equals failure
and intensification included endpoints (ITT). The number of patients
with new drug resistance mutations, HIV RNA in the CSF or change in
neurocognitive function was analyzed by treatment arm.
Poster Abstracts
Abstract P256Table 1. Number of patients with treatment
emergent NRTI, NNRTI or PI resistance mutations
NRTI or PI Resistance mutations
Trial (n, duration)
PI/r
Triple therapy
OK-04 (n 200, 96 wks)
2/100
2/98
Kalmo (n 60, 96 wks)
0/30
0/30
Kalesolo (n 186, 48 wks)
KRETA (n 88, 48 wks)
0/87
1/44
0/99
0/44
MOST (n 60, 24 wks)
0/29
0/31
DREAM (n 197, 96 wks)
3/11
LPV/r trials
DRV/r trials
MONET (n 256, 144 wks)
1/127
1/129
MONOI (n 246, 96 wks)
0/112
0/113
Monarch (n 30, 48 wks)
0/15
0/15
PROTEA (n 273, 48 wks)
Mixed PI trials
0/137
0/136
PIVOT (n 587, 5 years)
7/291
4/296
Results: Four trials evaluated darunavir/r monotherapy (n 785:
MONET, MONOI, MONARCH, PROTEA), five evaluated lopinavir/r
monotherapy (n 592: OK-04, KalMo, KALESOLO, KRETA, MOST) and
one evaluated both (MRC PIVOT, n587). HIV-1 RNA suppression
rates tended to be lower on PI monotherapy than triple therapy in
‘‘switch equals failure’’ analysis (76% vs 82%), but not when the
outcome of intensification was included (87% vs 85%). There were
small numbers of patients taking PI monotherapy with detectable
HIV-1 RNA in the CSF, in three trials: PROTEA (n 2), MONOI (n 2)
and MOST (n 5), but only two cases of CSF viral escape (MONOI).
In two trials, there was no difference in neurocognitive test results
between PI monotherapy and triple therapy, based on z-scores from
five domains (in PROTEA, mean change in NPZ-5 score0.0 for DRV/r
monotherapy vs 0.10 for triple therapy); similar results were
observed in the MRC PIVOT trial. The risk of treatment emergent
NRTI or PI resistance (Table 1) was 11/973 (1.1%) for patients on PI
monotherapy, versus 7/991 (0.7%) for patients on triple therapy.
Conclusions: In 10 randomised trials of 1964 patients with HIV-1 RNA
suppression at baseline, PI monotherapy showed a higher risk of HIV
RNA elevations, and small numbers with HIV RNA detectable in CSF
and concomitantly in the plasma. However there was no increased
risk of treatment-emergent drug resistance, neurocognitive endpoints were not different between the arms and HIV-1 RNA suppression rates after intensification were similar between PI monotherapy
and triple therapy.
P257
The efficacy, pharmacokinetics, safety and cardiovascular
risks of switching nevirapine to rilpivirine in HIV-1 patients:
the RPV switch study
Casper Rokx1; Maren Blonk2; Annelies Verbon1; David Burger2 and
Bart JA Rijnders1
1
Department of Internal Medicine, Erasmus University Medical
Center, Rotterdam, Netherlands. 2Department of Pharmacology,
Radboud University Medical Center, Nijmegen, Netherlands.
Introduction: Nevirapine (NVP) induces cytochrome P450 3A4 by
which rilpivirine (RPV) is metabolized. Switching NVP to RPV could
181
result in decreased RPV exposure with subsequent virological failure
and dyslipidemia because NVP is regarded as the least dyslipidemic,
non-nucleoside, reverse transcriptase inhibitor. This trial evaluated
the efficacy, pharmacokinetics, safety and cardiovascular risks of
switching NVP to RPV.
Materials and Methods: Prospective open label controlled trial.
HIV-1 patients with HIV-1 RNA B50 copies/mL on once daily NVP,
emtricitabine/tenofovir (FTC/TDF) switched to single tablet RPV/
FTC/TDF. Eligible patients on NVP, FTC/TDF were controls. Primary
endpoint was week 12 HIV-1 RNA B50 copies/mL by intention to
treat analysis. Secondary endpoints were week 24 HIV-1 RNA B50
copies/mL, NVP and RPV pharmacokinetics, safety and fasting lipids,
Framingham risk scores (FRS) and Adult Treatment Panel III (ATP-III)
lipid goals.
Results: Of 189 eligible patients, we included 50 RPV switchers and
139 NVP controls. Week 12 HIV-RNA was B50 copies/mL in 46/50
switchers (92.0%) which was not different from the hypothesized
90% week 12 suppression rate (p .431). Forty-four of 50 switchers
had week 24 HIV-1 RNA B50 copies/mL compared to 126/139
controls (difference: 2.6%, 95% CI 7.6% to 12.8%, p.593). NVP
plasma concentrations were below detection level in all at week 3.
Mean week 1 RPV trough concentration was 0.083 mg/L and
comparable to phase III trial data (p 0.747). Adverse events
occurred in 36 switchers, the majority (82.0%) were grade one.
Two switchers discontinued RPV for side effects. Significant changes
over 24 weeks (p B0.001) were observed in switchers on total
cholesterol (TC, 0.67 mmol/L, 95% CI 0.50 to 0.83), low density
lipoprotein (LDL)-C ( 0.36, 95% CI 0.21 to 0.51) and high
density lipoprotein (HDL)-C (0.28, 95% CI 0.20 to 0.35). The
TC/HDL-C ratio increased 0.20 (95% CI 0.02 to 0.37; p .029) and
systolic blood pressure decreased 6.0 mmHg (95% CI 1.7 to
10.3; p.007). The median FRS did not change over 24 weeks
(8.4% vs. 7.7%; p .119). More patients achieved LDL-C (15%;
p.016) and TC (25%; pB0.001) ATP-III treatment goals at week
24 on RPV.
Conclusions: A NVP to RPV switch does not influence RPV exposure
and results in adequate ongoing HIV-1 suppression. RPV could be an
option for patients at risk for cardiovascular diseases.
P258
Time on drug analysis based on real life data
Eugen Schülter1; Rolf Kaiser1; Maurizio Zazzi2; Anders Sönnerborg3;
Ricardo Camacho4 and Jens Verheyen5
1
Institute of Virology, University of Cologne, Cologne, Germany.
2
Department of Microbiology, University of Siena, Siena, Italy.
3
Clinical Microbiology and Infectious Disease, Karolinska Institute,
Stockholm, Sweden. 4Laboratory of Molecular Biology, Hospital Egas
Moniz, Lisbon, Portugal. 5Institute of Virology, University of DuisburgEssen, Essen, Germany.
Introduction: The health condition of HIV-1 infected patients has
improved during the last years, but lifelong antiretroviral treatment
is still needed. However resistance, multiple side effects and drug to
drug interactions of antiretrovirals challenge the establishment of a
long lasting regimen. The average running time of each antiretroviral
drug composing the therapy episodes combination antiretroviral
therapy (cART) may be seen as an indicator of effectiveness and
tolerability.
Materials and Methods: To evaluate the running time of each drug
used in HIV-1 treatment, we extracted therapy episodes from the
latest release of the EuResist database (www.euresist.org). The
evaluation period was from Oct 2006 to Oct 2012. Inclusion criteria
for this analysis were continuous patient monitoring for at least two
Poster Abstracts
years (i.e. latest therapy start in Oct 2010), and the extraction of at
least 100 cases per drug analyzed. Drug intake interruptions of less
than a month were ignored.
Results: At the time of data extraction (Feb 2013), the EuResist
database contained data from 61,953 patients of which 11,499
fulfilled the inclusion criteria. We obtained 37,035 drug treatment
lines from 38,153 cARTs and the overall average length of drug intake
was 18.7 months. For each single drug these average durations
measured in months were: 18.3 (3TC); 20.8 (ABC); 12.3 (d4T); 14.3
(ddI); 23.2 (FTC); 23.0 (TDF); 13.4 (ZDV); 19.8 (EFV); 21.9 (ETR); 17.7
(NVP); 19.2 (ATV); 22.7 (DRV); 18.7 (FPV); 17.9 (LPV); 15.2 (SQV); 14.6
(TPV); 22.6 (RAL); 21.9 (MVC) and 8.9 (T20). Overall drug discontinuation rates at one, two and three years were 35.0, 48.8 and 95.8%,
respectively. Average discontinuation rates for the different drug
classes at two years these were: 46.2% for NRTIs; 49.7% for NNRTIs;
55.4% for PIs and 37.6% for Raltegravir/Maraviroc.
Conclusions: In this cohort the overall frequency of therapy changes
is high. After two years of treatment, on average 49% of the patients
change at least one drug in their cART. Thus, we have to expect
numerous changes in the long term perspective of treatments. The
observed differences in durations suggest that newer drugs might
have advantages over older ones. However possible reasons and
confounding factors (such as number of past treatment lines, comedication, risk group, etc.) were not addressed at this time of the
analysis.
P259
Switch to raltegravir-based regimens and HIV DNA decrease
in patients with suppressed HIV RNA
Claudia Bianco1; Genny Meini2; Barbara Rossetti1; Silvia Lamonica3;
Annalisa Mondi3; Simone Belmonti3; Luri Fanti3; Nicoletta Ciccarelli3;
Simona Di Giambenedetto3; Maurizio Zazzi2 and Andrea De Luca1
1
Infectious Diseases Unit, Azienda Ospedaliera Universitaria Senese,
Siena, Italy. 2Medical Biotechnology Department, University of Siena,
Siena, Italy. 3Clinic of Infectious Diseases, Catholic University of
Sacred Heart, Roma, Italy.
Introduction: Raltegravir intensification is associated with an increase in 2-LTR episomal HIV DNA circles, indicating a persistent
low-level replication, in some individuals in ART with suppressed HIV
RNA. We aimed at monitoring residual plasma HIV RNA and cellular
HIV DNA in virologically suppressed patients switching to a
raltegravir-based regimen.
Materials and Methods: Forty-six HIV-infected subjects on PI or
NNRTI based-regimens, with plasma HIV RNA level B40 copies/mL
for ]6 months and CD4 200 cells/mL for ]12 months were
enrolled. Thirty-four patients switched to raltegravir-based regimen
(RASTA study group) and 12 continued a PI or NNRTI based-regimen
(control group). Ultrasensitive HIV residual viremia and total PBMC
HIV DNA were assessed at baseline (W0), 24 (W24) and 48 (W48)
weeks. HIV RNA levels were determined by an ultrasensitive test
derived from a commercial real time PCR (limit of detection 5 copies/
ml). A real time PCR was used to quantify HIV DNA copy numbers in
PBMCs.
Results: At W0, HIV DNA was detected in all patients while at W48 it
was detectable in 82.3% of RASTA group vs 100% of controls
(p 0.01). The difference between the average values of HIV DNA
log10 copies/1086 CD4 at W0 (median 3.11, IQR 2.703.45) and W48
(median 2.87, IQR 2.243.38) was statistically significant for RASTA
group (p0.035). Male gender (mean difference 0.37 log10
copies/1086 PBMC, p0.023) and previous PI based-ART (mean
difference 0.39 log10 copies/1086 PBMC, p0.036) were predictive
of HIV DNA level at W0. After adjusting for previous PI based-ART,
182
male gender was the only variable independently associated with HIV
DNA size at W0 (mean difference 0.326 log10 copies/1086 PBMC,
95% CI 0.641, 0.011 p0.043). Ultrasensitive HIV-1 RNA was
detectable at W0 in 50% of RASTA group versus 66.7% of controls and
at W48 in 32.4% versus 45.5%, respectively. No differences were
found between HIV RNA levels at W0 and W48 within and between
the two groups.
Conclusions: Switching to raltegravir-based regimens may be
associated with a decrease of HIV reservoir, as measured by total
PBMC HIV DNA. A larger sample size is required to confirm this
finding.
Poster Abstracts
References
1. Antiretroviral therapy for HIV infection in adults and adolescents.
Public Health Approach 2010 Revision. World Health Organization.
Geneva, Switzerland; ISBN 978 92 4 159976 4.
2. Integrated national guidelines on antiretroviral therapy, PMTCT of
HIV and infant & young child feeding. 2011, Ministry of Health,
Uganda.
3. What ARV regimen to switch to in adults, pregnant women and
children living with HIV (once-daily PI regimen)? WHO/HIV/2013.38,
World Health Organization 2013, Geneva, Switzerland.
4. App

hepatitis c - Journal of the International AIDS Society

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