AIDS research in Brazil Pedro Chequer, José Ricardo Pio Marins

Transcription

Introduction: AIDS research in Brazil
Pedro Chequer, José Ricardo Pio Marins, Cristina Possas, Julia Del Amo Valero, Francisco Inácio
Bastos, Euclides Castilho and Norman Hearst
Non-adherence among patients initiating antiretroviral therapy: a challenge for health
professionals in Brazil
Palmira de F. Bonolo, Cibele C. César, Francisco A. Acúcio, Maria das Graças B. Ceccato, Cristiane A.
Menezes de Pádua, Juliana Álvares, Lorenza N. Campos, Ricardo A. Carmo and Mark D.C. Guimarães
Self-perception of body changes in persons living with HIV/AIDS: prevalence and
associated factors
Claudia Paula Santos, Yone Xavier Felipe, Patricia Emilia Braga, Daniela Ramos, Rosana Oliveira
Lima and Aluísio Cotrim Segurado
Survival of AIDS patients using two case definitions, Rio de Janeiro, Brazil, 1986–2003
Dayse Pereira Campos, Sayonara Rocha Ribeiro, Beatriz Grinsztejn, Valdiléa G. Veloso, Joaquim
Gonçalves Valente, Francisco Inácio Bastos, Mariza Gonçalves Morgado and Angela Jourdan Gadelha
Characteristics and survival of AIDS patients with hepatitis C: the Brazilian National
Cohort of 1995–1996
José Ricardo Pio Marins, Marilisa Berti de Azevedo Barros, Helymar Machado, Sanny Chen, Leda
Fátima Jamal and Norman Hearst
Optimistic perception of HIV/AIDS, unprotected sex and implications for prevention
among men who have sex with men, São Paulo, Brazil
Cristiane G.M. da Silva, Dreyf de A. Gonçalves, Júlio C.B. Pacca, Edgar Merchan-Hamann and
Norman Hearst
Prevention of mother-to-child transmission of HIV in São Paulo State, Brazil: an update
Luiza Harunari Matida, Mariliza Henrique da Silva, Ângela Tayra, Regina Celina de Menezes Succi,
Maria Clara Gianna, Alexandre Gonçalves, Heráclito Barbosa de Carvalho and Norman Hearst
Factors associated with condom use among youth aged 15–24 years in Brazil in 2003
Gabriela Calazans, Teo W. Araujo, Gustavo Venturi and Ivan França Junior
Knowledge, practices and behaviors related to HIV transmission among the Brazilian
population in the 15–54 years age group, 2004
Célia Landmann Szwarcwald, Aristides Barbosa-Júnior, Ana Roberta Pascom and Paulo Roberto de
Souza-Júnior
Factors associated with institutionalization of children orphaned by AIDS in a populationbased survey in Porto Alegre, Brazil
Marlene Doring, Ivan França Junior and Isete Maria Stella
Sexually transmitted disease/HIV risk behaviour among women who have sex with
women
Valdir Monteiro Pinto, Mariza Vono Tancredi, Antonio Tancredi Neto and Cássia Maria Buchalla
Evaluation of rapid tests for anti-HIV detection in Brazil
Orlando C. Ferreira Junior, Cristine Ferreira, Maristela Riedel, Marcya Regina Visinoni Widolin and
Aristides Barbosa-Júnior for the HIV Rapid Test Study Group
Estimating the genetic component (RGC) in pharmacokinetic variability of the
antiretroviral didanosine among healthy Brazilians
Luciane S. Velasque, Rita de Cassia E. Estrela, Guilherme Suarez-Kurtz and Claudio J. Struchiner
HIV-1 subtype C dissemination in southern Brazil
Esmeralda A.J.M. Soares, Ana M.B. Martínez, Thatiana M. Souza, André F.A. Santos, Vanusa Da
Hora, Jussara Silveira, Francisco I. Bastos, Amilcar Tanuri and Marcelo A. Soares
INTRODUCTION
AIDS research in Brazil
Pedro Chequera, José Ricardo Pio Marinsa, Cristina Possasa,
Julia Del Amo Valerob, Francisco Inácio Bastosc, Euclides Castilhod and
Norman Hearste
AIDS 2005, 19 (suppl 4):S1–S3
This is the first supplement of AIDS in its 20-year history
devoted entirely to research in a single country. Why
now? And why Brazil?
Brazil has earned international notoriety in the fight against
AIDS. It is best known as the first developing country to
provide free, universal access to antiretroviral treatment
(ART) for all patients. In so doing, Brazil accomplished
what many believed impossible: effectively delivering
ART in a resource-limited setting while challenging the
norms of the international pharmaceutical industry. The
success of this effort shattered the illusion that ART could
only be for rich countries, jolted cautious international
organizations into action, and gave new hope not only
to millions of people living with HIV in the developing
world but also to their families and communities.
Brazil has also received international recognition for its
success in HIV/AIDS prevention. The Brazilian government, aided by a strong non-governmental organization
sector, responded early and vigorously to the epidemic
with activities targeting both vulnerable groups and the
general population. Prevention messages were characterized by frank, open discussion of sexuality and an
unwavering commitment to fighting stigmatization.
Although it is impossible to know exactly what would
have happened otherwise, these efforts are generally
credited with achieving relative stability in the number of
Brazilians infected with HIV at a much lower level than
initially projected.
But what about research? In its own way, Brazil’s
commitment to AIDS research has been no less
impressive than its commitment to treatment and
prevention. Brazil fits squarely in the ‘middle income’
category of nations, with highly developed sectors even
while large portions of the population remain poor and
uneducated. Although this uneven development creates
great challenges in the fight against AIDS, it also means
that Brazil has a cadre of professionals capable of
conducting AIDS research. Brazil has probably devoted
more resources to AIDS research than any other
developing country, and a great deal of high quality
research has been conducted. Until now, though, this has
often been invisible to the international community
because the results of this research have seldom been
published in top-quality international peer-reviewed
journals.
There are many reasons for this, and most of these are not
unique to Brazil. Beyond the obvious barrier of language
are more complicated barriers of culture. Many investigators in Brazil have neither the incentive nor the experience necessary to publish successfully in international
journals. They are likely to be much more familiar with
the extensive and comprehensive format of the thesis or
the final report to a funding agency than the 3000-word
haiku of the research article. Except for the minority of
AIDS researchers based in top universities and research
institutes, their jobs are unlikely to require them to
publish or perish.
a
Brazilian National STI/AIDS Control Program, Brasilia, Brazil, the bMiguel Hernandez University, Alicante, Spain, the cOswaldo
Cruz Foundation, Rio de Janeiro, Brazil, the dUniversity of São Paulo, São Paulo, Brazil, and the eUniversity of California, San
Francisco, CA, USA.
Correspondence to Norman Hearst, MD MPH, Professor of Family and Community Medicine and of Epidemiology and
Biostatistics, 500 Parnassus MU3E Box 0900, University of California, San Francisco, California 94143, USA.
Tel: +1 415 476 6364; fax: +1 415 476 6051; e-mail: [email protected]
ISSN 0269-9370 Q 2005 Lippincott Williams & Wilkins
Unauthorised copying and distribution of material is prohibited. Copyright is with original publisher.
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AIDS 2005, Vol 19 (suppl 4)
Consequently, the results of AIDS research in Brazil, even
high quality research, are not published in international
journals nearly as often as they should be. Dissemination is
more likely to be through presentations at conferences
and publications of the National AIDS Control Program
and other official agencies. Furthermore, analysis and
dissemination sometimes lack the rigor demanded by peer
review. Long reports allow investigators to avoid identifying, focusing upon, and fully justifying their key findings.
Whatever the reasons, this relative lack of formal, peerreviewed publication has unfortunate consequences.
Data gathered are not as productively analysed as they
should be. Findings often are not disseminated widely,
both within Brazil and especially internationally, meaning that they are less known and used than they should
be. A substantial proportion of studies published from
Brazil have been those directed by investigators from
rich countries, sometimes creating the false impression
that this represents the majority of AIDS research in
Brazil. Meanwhile, Brazilian researchers and research
institutions do not receive recognition for their work,
limiting their ability to compete for future research
funding.
In recent years, the Brazilian National AIDS Control
Program has become increasingly aware of this problem.
The program realized that requiring investigators to
publish their results in peer-reviewed journals would do
little good unless they and their institutions were
equipped with the skills and guidance they would need
to ‘play the game’. The program therefore embarked on a
multistep process to increase the publication of Brazilian
AIDS research.
The first step was to identify research projects, mostly
funded by the Brazilian government, which had
completed data collection and were believed to have
produced important findings that had not yet been
published in peer-reviewed journals. Over 30 such studies
were identified. Investigators of these studies, many based
in non-governmental organizations and public health
service settings, were contacted and invited to apply to
participate in a series of workshops on how to publish in
international journals. Sixteen teams of two investigators
from each study were selected to participate in a series of
four monthly workshops, each lasting 3–5 days. These
workshops were facilitated by investigators experienced
in publishing in international journals. They emphasized
peer review among the participants themselves and by
Brazilian experts. Before the final workshop, draft
manuscripts were professionally translated into English.
The final workshop involved international peer reviewers
who provided feedback on the English versions of the
manuscripts.
As a next step, the National AIDS Control Program
negotiated with AIDS to produce this supplemental issue.
Investigators who had participated in the workshops as
well as others who had not were invited to submit
manuscripts. Of the articles in this issue, all of which
passed through the AIDS peer review process, eight
resulted from the workshop series and five were direct
submissions.
The articles in this issue represent the broad range of
AIDS research in Brazil. Several draw lessons from the
extensive Brazilian experience with providing ART in a
resource-limited setting. The study by Bonolo et al. on
treatment adherence demonstrates levels of adherence
and barriers that are similar to what has been reported in
developed countries. Santos et al. examined one of these
barriers to adherence, self-perceived body changes
resulting from ART, in more detail. They found Brazilian
HIV/AIDS patients to be no less concerned about such
changes than their counterparts in richer countries.
Two reports apply the techniques of survival analysis to
examine specific questions in large cohorts of Brazilian
AIDS patients in the context of universal access to ART.
Campos et al. confirmed previous studies showing
improvements in survival among Brazilian AIDS patients
similar to those observed in rich countries and demonstrated continuing ongoing improvement. They also
demonstrated that the survival time can vary substantially
depending on the AIDS case definition used. Marins et al.
reported that AIDS patients co-infected with hepatitis C
have a shorter survival, but that this difference seems to be
largely caused by the co-infected patients receiving less
intensive ART than their counterparts without hepatitis
C infection.
Several other articles examined the Brazilian experience
with prevention. Silva et al. reported a potential unexpected consequence of treatment availability. Among
men who have sex with men, those who have more
optimistic perceptions about the efficacy of treatment are
more likely to practice unprotected anal intercourse.
Matida et al. demonstrated a more positive impact of
treatment on prevention by documenting the substantial
progress made in reducing mother-to-child transmission
of HIV in São Paulo State. Calazans et al. reported high
levels of condom use by young people in Brazil, especially
with casual partners, but also identified several predictors
of non-use. Szwarcwald et al. examined AIDS-related
knowledge and behavior in the broader adult Brazilian
population and found substantial socioeconomic disparities in risk, thus demonstrating the need to target future
prevention efforts towards the poor.
Two articles dealt with the needs of special populations
that have not received enough attention in AIDS
research. Doring et al. demonstrated that stigma and
racism remain serious barriers to finding foster homes for
AIDS orphans. Pinto et al. showed that Brazilian women
who have sex with women are often at a substantial risk of
AIDS research in Brazil: introduction Chequer et al.
HIV and other sexually transmitted infections, a risk that
is often unrecognized by them and their healthcare
providers.
Three articles are in the field of laboratory and basic
science, disproving any notion that such research can only
be performed in rich countries. The meticulous
evaluation by Ferreira et al. of the performance of HIV
rapid tests is of obvious practical value anywhere in the
world that such tests might be employed. Velasque et al.
provided insight into the pharmacokinetics of didanosine.
Soares et al. applied techniques of molecular epidemiology to document how HIV subtype C appears to be
displacing subtype B as the predominant strain in
southern Brazil.
Transcending the findings of each individual article in this
issue is one overall lesson. Research from developing
countries has just as much to contribute to the global fight
against AIDS as does research from rich countries. In
many ways, it is even more relevant to the poorer
countries with the vast majority of the world’s HIV
infections. Research in developing countries is also
relatively inexpensive because personnel costs (the biggest
category in most research budgets) are much lower. The
studies reported in this issue were conducted for only a
fraction of what it would cost to conduct similar research
in rich countries. Most had total budgets of under
US$100 000.
How much could be learned from the results of other
studies conducted elsewhere in the developing world that
were never published? How much more could have been
learned from studies that were never conducted for lack of
funding? How can we justify spending 95% of the world’s
AIDS research budget in rich countries? Equity and
efficiency cry out for investing far more in AIDS research
in the developing world.
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Non-adherence among patients initiating
antiretroviral therapy: a challenge for health
professionals in Brazil
Palmira de F. Bonoloa,e, Cibele C. Césarb, Francisco A. Acúrcioa,c,
Maria das Graças B. Ceccatoa, Cristiane A. Menezes de Páduaa,
Juliana Álvaresa, Lorenza N. Camposa, Ricardo A. Carmod and
Mark D.C. Guimarãesa
Objective: To assess the incidence, magnitude and factors associated with the first
episode of non-adherence for 12 months after the first antiretroviral prescription.
Design: A prospective study of HIV-infected patients receiving their first antiretroviral
prescription in public referral centers, Belo Horizonte, Brazil. Baseline assessment
occurred at the moment of the first prescription and follow-up visits at the first, fourth
and seventh month, from May 2001 to May 2003.
Methods: Non-adherence was self-reported and defined as the intake of less than 95%
of the prescribed doses for 3 days before the follow-up interviews. Cumulative and
person-time incidence were estimated and Cox’s proportional model was used to assess
the relative hazard (RH) of non-adherence with 95% confidence interval for both
univariate and multivariate analysis.
Results: Among 306 patients, the cumulative incidence of non-adherence was 36.9%
(incidence rate 0.21/100 person-days). Multivariate analysis (P < 0.05) showed that
unemployment (RH ¼ 2.17), alcohol use (RH ¼ 2.27), self-report of three or more
adverse reactions (RH ¼ 1.64), number of pills per day (RH ¼ 2.04), switch in antiretroviral regimen (RH ¼ 2.72), and a longer time between the HIV test result and the
first antiretroviral prescription (RH ¼ 2.27) were associated with an increased risk of
non-adherence, whereas the use of more than one health service indicated a negative
association (RH ¼ 0.54).
Conclusion: The current analysis has pointed out the importance of clinical and health
service characteristics as potential indicators of non-adherence after initiating therapy.
Early assessment and intervention strategies should be priorities in these AIDS public
referral centres. Feasible and reliable indicators for the routine monitoring of adherence
should be incorporated in clinical practice.
ß 2005 Lippincott Williams & Wilkins
AIDS 2005, 19 (suppl 4):S5–S13
Keywords: adherence, antiretroviral therapy, Brazil, HIV,
prospective study
From the Departments of aPreventive and Social Medicine, Faculty of Medicine, the bStatistics, Institute of Exact Sciences, the
c
Social Pharmacy, Faculty of Pharmacy, Federal University of Minas Gerais (UFMG), the dEduardo de Menezes Hospital, Minas
Gerais State Health Department and the eBelo Horizonte City Health Department, Division of Epidemiology, Belo Horizonte, MG,
Brazil.
Correspondence to Mark D.C. Guimarães, Department of Preventive and Social Medicine, Faculty of Medicine, Federal University
of Minas Gerais (UFMG), Av. Prof. Alfredo Balena 190, 108 andar, Belo Horizonte, MG, 30.130-100, Brazil.
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Introduction
Methods
The Brazilian National AIDS Program has implemented a
free and universal programme of antiretroviral distribution, which has brought considerable benefits to
patients [1]. The median survival time increased from 5
months in 1985 to approximately 60 months in 1996 [2],
whereas the occurrence of HIV-related opportunistic
infections has declined by 60–80% [3]. Such outcomes
have led to improvements in the quality of life of HIVinfected individuals and a reduction in the costs of
treatment and hospitalization for AIDS-related conditions [4].
Participants and design
Patients receiving their first antiretroviral prescription
were prospectively followed for non-adherence up to 12
months at two public AIDS referral centres, the Training
and Referral Center for Infectious and Parasitic Diseases
(CTR/DIP Orestes Diniz) and Eduardo de Menezes
Hospital (HEM), Belo Horizonte, Minas Gerais, Brazil.
However, benefits from antiretroviral therapy (ART) are
strongly associated with the level of patient adherence. As
a result of a high and constant rate of replication and
mutation of HIV, it has been suggested that a level of at
least 95% adherence is required in order to maintain
undetectable viral loads [5]. Non-adherence is not only
the most common cause of therapy failure, but it also
represents one of the most important factors that health
services can manage to reach a higher effectiveness of
treatment [6].
Rates of non-adherence have varied from 7.0 to 43.0%
[7–10] depending on the study design, target population,
measure of adherence, and duration of HIV treatment. In
addition, several factors have been found to be associated
with non-adherence to ART, including individual,
environmental, patient–provider interaction and biomedical characteristics such as adverse reactions, complexity
of therapy, and stage of HIV disease [11,12]. Understanding such factors, especially among those who are
initiating ART, is the key for the development of
interventions to improve adherence and to sustain longterm treatment benefits.
There are a few studies concerning adherence to ART in
Brazil, most of which are cross-sectional and with patients
under treatment for long periods. Methodological issues,
in particular the definition of adherence, sources of
information and representativeness make a comparison of
such studies difficult. Nevertheless, the high proportion
of non-adherence, from 14.2 to 43.1% [6,13,14], is
similar to rates observed in developed countries, which is
of public health concern.
The present study is one of the first follow-up studies in
Brazil and provides an opportunity to evaluate factors
associated with non-adherence among patients receiving their first antiretroviral prescription in public health
settings. An early understanding of non-adherence
within our cultural and socio-economic contexts may
contribute to the development of strategies aimed at
intervention.
Recruitment occurred from May 2001 to May 2002 and
patients were followed up to May 2003. Inclusion criteria
were patients with confirmed HIV infection who met
Brazilian guidelines to initiate ART [15], had never taken
any antiretroviral drug before, were 18 years old or over,
signed a written informed consent, and had their
antiretroviral drugs dispensed in one of the centres.
Pregnant women were not considered eligible for the
current analysis because of specific features of their ART
(e.g. duration of treatment, antiretroviral regimen).
Participants were assessed soon after receiving their first
antiretroviral drugs from the pharmacies at each centre
(baseline interview), and in the first, fourth, and seventh
months after initiating therapy (follow-up visits). The
maximum follow-up period was established at 12 months.
The present analysis aimed at assessing the first episode of
non-adherence among patients who returned for at least
one follow-up visit during the study period.
Exposure and outcome measurements
Standardized and tested forms were used for the
interviews as well as for laboratory and clinical data
collected from medical charts. For the purpose of this
analysis, exposure variables have been grouped as follows:
(i) sociodemographic characteristics (age, sex, race,
schooling, marital status, income, source of HIV
infection, employment, health insurance plan and
religious activities); (ii) behaviour characteristics (communicating their HIV status to someone, living with
someone who was also HIV tested, alcohol, illicit drug,
tobacco and condom use); (iii) health services-related
characteristics (recruitment site, difficulty in searching for
HIV service, interval between regular medical visits
greater than 6 months, use of more than one health
service for HIV care, psychological support, number of
visits with infectologists, and receiving and understanding
medical counselling related to antiretroviral agents); (iv)
clinical characteristics (antiretroviral regimen, number of
pills per day, ART switch, clinical classification, CD4
lymphocyte T-cell count, adverse reactions, time between
HIV test result or first medical visit and antiretroviral
prescription).
Sociodemographic, behaviour, health services and
clinical characteristics were assessed during baseline
interviews, whereas the use of antiretroviral agents,
adherence (self-report) and occurrence of adverse
Non-adherence to antiretroviral therapy Bonolo et al.
reactions were assessed during follow-up interviews.
Medical charts originated clinical and immunological
data over the study period, which were classified
according to the Centers for Disease Control and
Prevention definition [16].
Medical counselling related to antiretroviral prescription
included the following items: name, doses, schedule, food
intake, use of alcohol, adverse reactions, what to do if
antiretroviral agent was forgotten or when therapy was
interrupted and when to return for antiretroviral delivery.
Counselling was considered adequate if patients were
informed of at least six of these items [17]. Time between
the HIV test result and the first antiretroviral prescription
was categorized using its median value whereas age was
assessed as a continuous variable.
Adverse reactions were defined as any effects or
undesirable symptoms reported by the patient over the
study period attributed to the antiretroviral drug. The
questionnaire included a list of gastrointestinal (e.g.
diarrhoea, nausea), dermatological (e.g. rash), neurological (e.g. insomnia, hallucination), and other freely
reported signs or symptoms.
The measurement of adherence was self-reported
obtained through standard interview, and was defined
as the number of prescribed doses of each antiretroviral
drug taken during the 3 days before each follow-up visit.
For those patients who had their regimen switched, the
current antiretroviral drug at the time of interview was
considered. Only the first occurrence of non-adherence
was assessed and was defined as the intake of less than 95%
of the prescribed number of doses.
Statistical analysis
The cumulative and person-time incidences of nonadherence were estimated. For both, the numerator was
the number of patients taking less than 95% of the
prescribed number of antiretroviral doses during the 3
days before the interview. The denominator was the
number of patients who returned for at least one followup visit for the former and the sum of the times
contributed by each individual for the latter. Time was
defined as the number of days between the date of the
baseline interview and the date of the interview,
indicating the first non-adherence episode or date of
the last interview for those considered to be adherent.
Patients who did not return for at least one visit were
considered lost to follow-up.
The magnitude of the association between selected
exposure variables and the first non-adherence episode
was estimated by the relative hazard (RH) with 95%
confidence interval, obtained from Cox’s proportional
hazard model [18] for both univariate and multivariate
analysis. The level of significance considered for the final
model was 0.05 in order better to ascertain potential
confounders.
Multivariate modelling was initially carried out for each
group of variables separately (sociodemographic, behaviour, health service and clinical characteristics). For each
one, a full model was started with variables found to be
statistically associated with the first episode of nonadherence in the univariate analysis (P < 0.20). Explanatory variables were sequentially deleted within each
group, and only those found to be statistically associated
with the outcome at a P value smaller than 0.10 were
retained. We defined these as intermediate models. Final
modelling was started with those variables statistically
significant (P < 0.10) in each intermediate model
followed by sequential deletion. Only those found to
be associated with non-adherence (P < 0.05) remained
in the final model as explanatory variables. Finally, a
likelihood ratio test was used to compare all models, and
the proportional hazard assumption was assessed by
checking the parallelism of the log–log survival curves
and the Schoenfeld test [19].
Results
Descriptive analysis
Among the 417 patients recruited who met the elegibility
criteria for the current analysis, 350 (83.9%) agreed to
participate and 306 (73.4%) returned for at least one
follow-up visit. No statistically significant difference was
observed between participants and non-participants or
those lost to follow-up regarding age, sex or site of
medical assistance. In addition, censorship and event were
independent, as compared with medical charts
(P ¼ 0.952). The mean overall follow-up time was 215
days (median 247) and the mean time between the
baseline and first visit was 41 days.
Descriptive characteristics presented in Table 1 indicate
that the studied population is similar to the Brazilian
AIDS cases reported nationally [20]; in particular, lower
schooling and income and a high proportion of Afrodescendent and heterosexually acquired HIV infection.
The high proportion of unemployment (35.9%) and lack
of any private health insurance plan (75.8%) should also
be noted. The majority had communicated their HIV
status to someone close, and reported living with
someone who had also been tested for HIV. Despite
the high proportion of ever using alcohol, this decreased
to 37.6% in the month before the baseline interview.
Although most patients attended only one health service
and were recruited at the CTR/DIP centre, difficulty in
finding HIV medical assistance, irregular medical visits or
psychological support were reported by fewer patients.
On the other hand, 79.4% received medical counselling
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Table 1. Selected descriptive characteristics among 306 participants who had at least one follow-up visit, Belo Horizonte (MG), 2001–2003.
Characteristics
Sociodemographics
Age (< 35 years old)
Sex (male)
Race (Afro-descendent)
Schooling ( 8 years)
Marital status (single)
Individual income (US$ 80)b
Source of HIV infection (heterosexual)
Unemployed
Fixed job schedule
Private health insurance plan (no)
Religious activities (yes)
Behaviour
Communicated their HIV status to someone close
Lived with someone who had also been tested for HIV
Ever used alcohol
Alcohol use in month before the baseline interview
Ever used injecting drug
Ever used any illicit drug
Current tobacco use
Lifetime condom use (rarely/never)
Health service
Recruitment at the CTR/DIP service
Difficulty in searching for HIV service
Interval between regular medical visits (> 6 months)
Attended only one health service for HIV care
Psychological support
Number of Infectologist visits (> 6)
Adequate medical counselling (> 6 items)
Complete understanding of medical counselling
Clinical
Antiretroviral regimen (triple or more)
Antiretroviral regimen with protease inhibitors
Initial regimens:
Zidovudine/lamivudine/efavirenz
Zidovudine/lamivudine/nelfinavir
Zidovudine/lamivudine/nevirapine
Others
Total number of prescribed pills per day
<7
7–12
> 12
Switched antiretroviral drugs (at least once)
Clinical classification (symptomatic)
CD4 T-lymphocyte count (< 200 cells/ml)
Adverse reactions ( 3)
Time between HIV test and first antiretroviral prescription ( 113 days)
Time between first medical visit and first antiretroviral prescription ( 42 days)
na
%
153
199
218
168
144
175
228
110
137
232
147
50.0
65.0
74.4
55.1
47.1
57.9
75.0
35.9
69.9
75.8
48.0
255
132
261
111
17
83
101
196
86.4
57.1
88.8
37.6
6.0
28.1
34.2
67.1
248
27
44
227
16
100
243
212
81.0
9.2
14.4
76.9
5.4
33.0
79.4
73.4
305
147
99.7
48.0
91
69
42
104
29.7
22.6
13.7
34.0
136
140
30
66
168
156
146
158
162
44.4
45.8
9.8
21.6
56.7
57.3
57.7
50.0
52.9
CTR/DIP, Training and Referral Center for Infectious and Parasitic Diseases.
a
Total for each variable differs as a result of missing values.
b
One minimum wage.
on at least six items related to antiretroviral agents, with a
reasonable proportion showing complete understanding
of such information.
Clinical characteristics indicated that 99.7% initiated
treatment with three or more antiretroviral regimens,
with zidovudine and lamivudine present in most of them.
Whereas fewer patients took more than 12 pills per day or
switched therapy during follow-up, most of them were
clinically symptomatic with a CD4 lymphocyte T-cell
count of 200 cells/ml or less when initiating treatment.
Finally, more than three adverse reactions to antiretroviral
drugs were reported by 57.7% of the patients (median 3,
range 1–15), and the most common were nausea (11.7%),
stomach burn or stomach ache (8.9%) and tiredness
(8.3%).
Adherence assessment
The overall cumulative incidence was 36.9% and the
incidence rate was 0.21/100 person-days. Among the 113
participants who had their first non-adherence episode
during the study period, it occurred in the first, second
and third follow-up visit for, respectively, 57.5, 31.0 and
11.5%, emphasizing the early impact of ART in this
population.
and having a longer period between the HIV test result
and the first antiretroviral prescription (P < 0.001).
Univariate analysis indicated that non-adherence was
statistically associated (P < 0.05) with female sex, lower
schooling ( 4 years), lower individual income, being
unemployed and not having any health insurance plan
(Table 2). However, Afro-descendent race, being divorced
or widowed, having a fixed job schedule or religious
activities also showed associations with P values varying
from 0.05 and 0.20.
The final overall model (Table 3) (P 0.05) indicated
that being unemployed (P ¼ 0.011), making use of
alcohol in the month before the baseline interview
(P < 0.001), using more than one health service
(P ¼ 0.002), taking more than 12 prescribed pills per
day (P ¼ 0.02), reporting three or more adverse reactions
(P ¼ 0.017), switching ART (P < 0.001), and a longer
time between the HIV test result and the first
antiretroviral prescription (P < 0.001) were the only
variables that remained statistically associated with an
increased risk of non-adherence in this population. The
proportional hazards assumption was satisfied according
to both methods and no violation was verified
(Schoenfeld test 12.33; P ¼ 0.196).
Similarly, behaviour and health service characteristics
indicated an increased risk of non-adherence (P < 0.20)
for those who communicated their HIV status to
someone close, lived with someone who had also been
tested for HIV, were current smokers, were recruited in
one of the centres (CTR/DIP), had psychological
support, had six or more infectologist visits and received
inadequate medical antiretroviral counselling (less than six
items). However, only those who used alcohol (in the
month before the baseline interview), used illicit drugs
(lifetime) and used injecting drugs (lifetime) were found
to be associated at a P value of less than 0.05. On the other
hand, a negative association with non-adherence was
found for patients who reported using more than one
health service.
Finally, univariate analysis of clinical characteristics
indicated that the number of prescribed pills per day,
having at least one ART switch, a baseline CD4
lymphocyte T-cell count greater than 200 cells/ml,
reporting three or more adverse reactions to antiretroviral
drugs and having longer period between HIV test result
or first medical visit and first antiretroviral prescription
were statistically associated with non-adherence
(P 0.05). This clearly emphasizes the relevance of
clinical aspects in the initial period of treatment. It should
be noted that being asymptomatic showed an increased
risk, although not statistically significant (P ¼ 0.182).
Multivariate analysis
Table 3 shows the results of the multivariate intermediate
and final modelling in order to compare the potential
explanatory factors. Intermediate analysis indicated the
following variables to be associated with non-adherence
within each group, considering a P value of 0.10 or less or
borderline: (i) sociodemographic characteristics: Afrodescendent race (P ¼ 0.044), being married (P ¼ 0.082),
having a fixed job schedule (P ¼ 0.116), being unemployed (P ¼ 0.002) and not having any religious activities
(P ¼ 0.027); (2) behaviour characteristics: use of alcohol
(P ¼ 0.012) or illicit drugs (P ¼ 0.038); (iii) health
services: using more than one health service (P ¼ 0.053)
and having psychological support (P ¼ 0.049); and (iv)
clinical characteristics: taking more than 12 prescribed
pills per day (P ¼ 0.09), switching ART (P < 0.001),
reporting three or more adverse reactions (P ¼ 0.016),
Discussion
To our knowledge, this is the first prospective study in
Brazil that has assessed the initial impact of ART. These
are public health referral centres and covered approximately 90% of the reported AIDS cases in Belo Horizonte
during the study period. In addition, patients under care
show similar sociodemographic characteristics compared
with current trends in the Brazilian AIDS epidemic [20].
The cumulative incidence of non-adherence (36.9%)
found in this study was high, and most cases occurred
within the first follow-up visit (median time 41 days),
strongly suggesting that early assessment and intervention
strategies should be priorities in these AIDS public
referral centres.
The results point out the importance of clinical and health
service-related variables as potential indicators of nonadherence. Some of these are consequences of ART itself,
such as the presence of adverse reactions, pill burden and
the switch of regimens during the course of treatment.
Others, however, are clearly associated with access to
health services before initiating treatment, such as the late
initiation of treatment, medical counselling and time
between the test result or the first HIV medical visit and
treatment.
The observed association of non-adherence with a longer
time between the HIV test result and the first
antiretroviral prescription could be a consequence of
irregular routine clinical care [21]. Because of the
overload of patients, these services tend to give priority
to those with more severe clinical conditions, who may
also be more aware of the complications resulting from
non-adherence [22]. Interruption or irregularity of
medical visits before initiating or during therapy could
potentially jeopardize proper counselling, thus reducing
adherence to treatment and strongly emphasizing the
S9
S10
Table 2. Univariate analysis of the first episode of antiretroviral non-adherence, Belo Horizonte (MG), 2001–2003 (n U 306).
Characteristics
Sociodemographics
Aged
Sex
Female
Male
Race
Afro-descendent
White
Schooling
4 years
5–8 years
> 8 years
Marital status
Divorced/widowed
Married
Single
Individual incomee
US$80
> US$80
Source of HIV infection
IDU
MSM
Heterosexual
Employment
Unemployed
Fixed job schedule
Non-fixed schedule
Health insurance plan
No
Yes
Religious activities
None
Regular
Behaviour
Communicated their HIV status
Yes
No
Totala
Non-adherence n (%)b
306
–
0.99 (0.97–1.01)
0.380
107
199
50 (46.7)
63 (31.7)
1.50 (1.04–2.18)
1.00
0.031
218
75
87 (39.9)
22 (29.3)
1.55 (0.97–2.47)
1.00
0.068
83
85
137
39 (46.9)
29 (34.1)
24 (32.4)
1.80 (1.08–2.99)
1.29 (0.75–2.21)
1.00
0.024
0.362
54
108
144
24 (44.4)
42 (38.9)
47 (32.6)
1.57 (0.96–2.57)
1.26 (0.83–1.92)
1.00
0.073
0.271
175
127
75 (42.9)
37 (29.1)
1.61 (1.08–2.39)
1.00
0.018
11
65
226
7 (63.6)
22 (33.8)
81 (35.8)
2.16 (1.00–4.68)
0.91 (0.57–1.46)
1.00
0.051
0.317
110
137
59
51 (46.4)
48 (35.0)
14 (23.7)
2.16 (1.20–3.91)
1.46 (0.81–2.65)
1.00
0.011
0.210
232
74
92 (39.7)
21 (28.4)
1.65 (1.03–2.65)
1.00
0.039
159
147
64 (40.2)
49 (33.3)
1.28 (0.88–1.86)
1.00
0.191
255
40
98 (38.4)
11 (27.5)
1.60 (0.86–2.99)
1.00
0.137
55 (41.7)
31 (31.3)
1.42 (0.91–2.21)
1.00
0.123
75 (42.9)
37 (29.1)
1.61 (1.08–2.39)
1.00
0.018
11 (64.7)
98 (35.2)
2.17 (1.16–4.05)
1.00
0.015
40 (48.2)
69 (32.5)
1.71 (1.15–2.53)
1.00
0.007
42 (41.6)
67 (34.5)
1.42 (0.96–2.09)
1.00
0.075
75 (38.3)
33 (34.4)
1.14 (0.81–1.61)
1.00
0.459
98 (39.5)
15 (25.9)
1.42 (0.82–2.44)
1.00
0.208
12 (44.4)
96 (36.1)
1.02 (0.68–1.51)
1.00
0.927
18 (40.9)
95 (36.3)
0.99 (0.60–1.64)
1.00
0.973
20 (29.4)
89 (39.2)
0.66 (0.41–1.08)
1.00
0.103
Lived with someone HIV tested
Yes
132
No
99
Alcohol use in the month before baseline interview
Yes
111
No
184
Injecting drug use (lifetime)
Yes
17
No
278
Illicit drug use (lifetime)
Yes
83
No
212
Tobacco (current use)
Yes
101
No
194
Condom use (lifetime)
Rarely/never
196
Always/most of the time
96
Health service
Recruitment sites
CTR/DIP
248
HEM
58
Difficulty in searching for AIDS services
Yes
27
No
266
Interval between medical visits before HIV treatment
> 6 months
44
6 months
262
Used more than one health service
Yes
68
No
227
Relative hazardc (95% CI)
P value
Table 2 (continued )
Characteristics
Totala
Non-adherence n (%)b
Yes
278
106 (38.1)
No
16
3 (18.7)
Infectologist visits
6
100
42 (42.0)
<6
206
71 (34.5)
Adequate medical counselling (> 6 items)
No
89
38 (42.7)
Yes
217
75(34.6)
Medical counselling understanding
Low comprehension
25
12 (48.0)
Median comprehension
51
22 (43.1)
High comprehension
212
72 (34.0)
Clinical
Antiretroviral therapy (with protease inhibitor)
Yes
147
58 (39.5)
No
159
55 (34.6)
Number of prescribed pills/day
<7
136
42 (30.9)
7–12
140
55 (39.3)
> 12
30
16 (53.3)
Switched antiretroviral therapy
Yes
66
44 (66.7)
No
240
69 (28.7)
Clinical classification
Asymptomatic (A)
128
56 (43.7)
Symptomatic (B/C)
168
54 (32.1)
CD4 T-lymphocyte count
> 200 cells/ml
116
51 (44.0)
200 cells/ml
156
47 (30.1)
Adverse reactions
3
146
81 (46.0)
<3
159
21 (24.0)
Time between HIV test result and first antiretroviral prescription
113 days
158
71(46.4)
< 113 days
158
42 (27.4)
Time between first medical visit and first antiretroviral prescription
42 days
162
69 (42.6)
< 42 days
144
44 (30.6)
Relative hazardc (95% CI)
P value
1.55 (0.82–2.92)
1.00
0.177
1.30 (0.89–1.91)
1.00
0.177
1.33 (0.90–1.97)
1.00
0.148
1.41 (0.76–2.60)
1.18 (0.73–1.90)
1.00
0.271
0.504
1.13 (0.78–1.63)
1.00
0.521
1.0
1.24 (0.83– 1.86)
1.76 (0.99– 3.14)
0.292
0.054
2.68 (1.84–3.92)
1.00
< 0.001
1.24 (0.90–1.69)
1.00
0.182
1.61 (1.08–2.40)
1.00
0.018
2.00 (1.34–2.99)
1.00
< 0.001
2.00 (1.36–2.94)
1.00
< 0.001
1.50 (1.03–2.20)
1.00
0.035
CI, Confidence interval; CTR/DIP, Training and Referral Center for Infectious and Parasitic Diseases; HEM, Eduardo de Menezes Hospital; IDU,
injection drug users; MSM, men who have sex with men.
a
The total for each variable differs as a result of missing values.
b
Number and proportion of non-adherence.
c
Relative hazard obtained from Cox’s proportional model with confidence interval.
d
Age as a continuous variable.
e
One minimum wage.
P 0.05.
P 0.001.
need for an early assessment of potential non-adherents
[6,23,24]. Similarly, the negative association between the
use of more than one health service and non-adherence
suggests that support of other health professionals may
have a positive influence on antiretroviral adherence, as
mentioned by Spire et al. [22]. Patients with access to
private or non-governmental health services may have
additional benefits such as ease of access, follow-up and
laboratory appointments.
Adverse reactions, pill burden and regimen switch have
been consistently associated with antiretroviral nonadherence [6,10,15,22,24,25]. The present study also
indicated that these factors are associated with non-
adherence in the initial period of treatment. Duran et al.
[10] pointed out that the perception of symptoms
constitutes a critical factor for adherence among patients
observed up to the fourth month of treatment. Adverse
reactions, toxicities and the number of pills constitute
obstacles that challenge the patients’ ability to organize
their everyday activities and work tasks. This could
potentially lead to the interruption of treatment. A switch
in regimen at the beginning of treatment may well be a
consequence of both pill burden and side-effects, rather
than therapeutic failure.
In addition to clinical aspects, sociodemographic and
behavioural characteristics should not be underestimated,
S11
S12
Table 3. Relative hazard with 95% confidence interval obtained from multivariate analysis for each intermediate and final models, Belo
Horizonte (MG), 2001–2003.
Intermediate models
Variables
Race (Afro-descendent)b
Marital status (married)
Employmentc
Fixed job schedule
Unemployed
No religious activities
Alcohol use (last month)
Illicit drug use (ever)
Used more than one health service
Number of prescribed pills/dayd
7–12
> 12
Adverse reactions ( 3)
Switched antiretroviral therapy
Time HIV prescription (> 113 days)e
Sociodemographics
Behaviour
Health service
Clinical
Final modela
1.64 (1.01–2.66)
1.47 (0.95–2.26)
–
–
1.66 (0.88–3.11)
2.66 (1.42–4.97)
1.56 (1.05–2.32)
1.44 (0.79–2.63)
2.17 (1.19–3.96)
–
2.27 (1.58–3.25)
–
0.54 (0.36–0.80)
–
1.64 (1.12–2.42)
1.53 (1.02–2.29)
0.66 (0.43–1.01)
2.38 (1.00–5.66)
1.12
1.68
1.65
2.38
2.14
(0.74–1.68)
(0.92–3.10)
(1.10–2.50)
(1.62–3.51)
(1.44–3.18)
1.35
2.04
1.64
2.72
2.27
(0.88–2.06)
(1.11–3.76)
(1.09–2.48)
(1.84–4.03)
(1.52–3.40)
a
Schoenfeld global test: 12.33; P ¼ 0.196.
Parentheses indicate risk category.
c
Compared with those with non-fixed job schedules, fitted as dummy.
d
Compared with less than seven pills per day, fitted as dummy.
e
Time between HIV test result and antiretroviral prescription, cut-off point equals median time.
b
as shown by other authors. They include female sex [26],
low income and schooling [14,15,22], use of alcohol
[10,12], use of illicit drugs [12], use of injecting drugs [12]
and tobacco [10]. The current findings corroborate these
authors, although only alcohol use and being unemployed
remained in the final model (RH 1.91 and RH 2.38,
respectively). Unemployment and lack of financial
resources may contribute to a decrease in self-care
motivation and negatively influence the patient’s capacity
to deal with ART on a daily basis.
In addition to widescale access to medication, ART goals
should include achieving and sustaining optimal treatment outcomes. Interventions must clearly focus on
counselling, social and work support, and on clinical
procedures such as the regularity of medical visits,
continuous monitoring of adverse reactions and adjustments in therapeutic regimens. Easing access to health
services and the establishment of multidisciplinary teams
will certainly contribute to the increase in adherence
among the population under study.
Finally, it must be pointed out that strategies of early
intervention must be developed, even before ART is
started. Designing and implementing feasible indicators
of adherence should be of great concern for programmes
with universal access to antiretroviral agents such as the
one in Brazil. This would help prevent or minimize
further HIV drug resistance and ensure better treatment
outcomes. The challenge to reach optimum levels of
adherence must be the immediate responsibility of health
services at all levels, shared by health professionals and
patients.
Acknowledgements
The present study would not have been possible without
the co-operation of HIV-infected individuals, who took
their time to answer the questionnaires. This study is part
of the ATAR Project (Adherence to Antiretroviral)
developed by the Research Group in Epidemiology and
Health Evaluation, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Sponsorship: This research had financial support from
the Pan-American Health Organization (OPAS/WHO)
and the Brazilian National AIDS/STD Program,
UNESCO, Ministry of Health.
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S13
Self-perception of body changes in persons living with
HIV/AIDS: prevalence and associated factors
Claudia Paula Santosa, Yone Xavier Felipea,c, Patricia Emilia Bragab,
Daniela Ramosa, Rosana Oliveira Limaa and Aluı́sio Cotrim Seguradoa
Background: Highly active antiretroviral therapy has brought about a substantial
improvement in the prognosis of HIV/AIDS. In this context, therapy-related body
changes (lipodystrophy) gain in importance, in light of the psychological distress they
cause and of their association with adherence to treatment. This study analyses patients’
self-perception of central fat gain (CFG) and peripheral fat loss (PFL).
Methods: A total of 457 patients were interviewed in a university outpatient facility for
the treatment of adults and adolescents with HIV/AIDS in the city of São Paulo, Brazil,
between September and December 2001.
Results: Two-thirds of subjects (64.3%) perceived body changes. The self-perception of
CFG and PFL was associated with greater schooling. The self-perception of CFG was
more frequent among women and in patients who used protease inhibitors for longer
periods. The self-perception of PFL was more frequent among older patients, patients
who used stavudine for longer periods, and patients who reported a lack of adherence to
antiretroviral agents. The quality of affective/social relationships with friends and family
was inversely associated with the self-perception of PFL.
Conclusion: The evaluation of self-perceived body changes and their determinants in
individuals living with HIV/AIDS may help improve provided care. Listening to what
patients have to say concerning antiretroviral therapy-related body changes and how
they perceive them, as well as including the patient in therapeutic decisions in this
regard will contribute towards greater adherence to proposed interventions and towards
an improvement in the quality of life.
AIDS 2005, 19 (suppl 4):S14–S21
Keywords: body changes, body image, Brazil, HIV/AIDS, lipodystrophy,
prevalence, self-perception
Introduction
Highly active antiretroviral therapy (HAART) has caused
profound alterations in HIV/AIDS prognosis [1–5], as
well as in the meanings around the epidemic, which have
shifted from images of a transmissible disease that was
potentially fatal within a short period of time to those of a
chronic clinical condition [6,7].
This scenario, on the other hand, has led to the need to
face patients’ long-term adherence to treatment [8,9] and
its adverse effects so as to provide better comprehensive
care to individuals living with HIV. In this context, body
changes gain increased significance. From 1998 onwards,
a particular set of body changes began to be recognized in
these patients, especially when under treatment with
HAART. This set of changes includes the loss of fat in
peripheral areas (face, buttocks, arms and legs) and the
gain of fat in central portions of the body (abdomen and
neck), and is known as the lipodystrophy syndrome. Body
changes are frequently accompanied by metabolic
disorders, characterized by hyperlipidemia and glucose
resistance [10]. Although lipodystrophy involves elements
related to both the redistribution of body fat and
From the aCasa da AIDS, Hospital das Clinicas, School of Medicine, the bSchool of Public Health, University of São Paulo and the
c
São Judas Tadeu University, São Paulo, Brazil.
Correspondence to Aluı́sio C. Segurado, R. Frei Caneca, 557, 01307-001 São Paulo, SP, Brasil.
Tel: +55 11 30667018; fax: +55 1130884945; e-mail: [email protected]
S14
Self-perception of body changes Santos et al.
metabolic disorders, the visual evidence of body changes
has, per se, an impact on the quality of life of those living
with HIV/AIDS [6].
The majority of studies investigating the prevalence of
body changes and factors related to it are based upon
clinical definitions; that is, they assume or imply the
participation of an external observer in diagnosing
the condition [11–14]. However, it is well known that
the individual perception of body changes may be
independent of the perception of such changes by other
individuals, or even from the objective measurement of
body composition by means of sophisticated diagnostic
methods [6].
Convinced that the adequate management of this issue
requires the active involvement of individuals living with
HIV in the decisions involving their care, we carried out
the present study, conceived from a different standpoint
for the interpretation of body changes described in/by
these individuals. Focusing on the self-perception of body
changes, we attempted to estimate the prevalence of
and to identify the factors associated with self-perceived
central fat gain (CFG) and peripheral fat loss (PFL) in a
sample of patients with HIV/AIDS attending a specialized reference centre in the city of São Paulo, Brazil.
Subjects and methods
We conducted a cross-sectional study between September
and December 2001 at the Casa da AIDS (AIDS Clinic)
of the University of São Paulo School of Medicine
Hospital. This is a university outpatient facility, located in
the city of São Paulo, and specializes in providing
multiprofessional care to adolescents and adults living
with HIV/AIDS. At the time of the survey, approximately 3500 patients were being followed at this facility.
Taking 46% as the estimated mean prevalence of body
changes in individuals living with HIV [13], we calculated
a sample size of 453 individuals (a ¼ 0.05 and b ¼ 0.20).
During the study period, the first 10 patients who came to
the clinic each day for blood sample collection for
laboratory monitoring tests (peripheral blood CD4 cell
count) were invited to participate in the survey. Patients
are submitted to these routine tests every 3 months, and
enrolment went on until the sample size was completed.
Patients presenting with active AIDS-defining illnesses
and those who reported previous plastic surgery interventions were excluded. After an explanation of the aims
of the study, patients who agreed to participate were
admitted after signing an informed consent form.
Subjects answered a standardized questionnaire, administered individually by one of the researchers at a private
location. The purpose of the questionnaire was to obtain
information on sociodemographic characteristics, sexual
activity, clinical and psychosocial aspects of living with
HIV, including antiretroviral treatment. All data related to
medication use were confirmed by reviewing medical
charts and antiretroviral dispensation files available at the
facility.
We defined the outcome of the study as the reported selfperception of body changes. These were defined on the
basis of the answer provided to the question addressing
the self-perception of an increase or reduction of
whatever severity in at least one specific body part,
including face, neck, stomach, chest, waist, arms, legs or
buttocks. We also asked patients to state when they first
noticed such changes, to what factors they attributed
them, whether the changes had been addressed by the
physician responsible for their clinical follow-up, and
whether this physician had given any recommendation
regarding these changes. For purposes of analysis we
defined two distinct patterns of changes, as suggested in
the literature [13]: CFG: a perception of an increase in the
neck, chest, waist, or stomach; PFL: a perception of a
reduction in the face, arms, legs, or buttocks.
We subsequently assigned reported body changes to
either, both or neither of those two categories.
Data obtained from the questionnaires were entered into
a Microsoft Excel database (Microsoft Corp., Redmond,
Washington, USA). Statistical analyses were carried out
using the STATA statistical package version 8 (STATA
Corp., College Station, Texas, USA).
We estimated the prevalences of the outcomes body
changes, CFG, and PFL with their associated 95%
confidence intervals (CI). In order to evaluate factors
associated with CFG and PFL, we considered them to be
dependent variables in models in which independent
variables were: sex, age, schooling, income, professional
activity, active sex life, time since diagnosis, use of
antiretroviral treatment (drug regimens and duration of
therapy), lack of adherence to therapy (‘dose skipping’,
missing at least one dose, regardless of the pill), disclosure
of diagnosis to sexual partner, and quality of interpersonal
relationships with partner, friends/family, and the healthcare team [self-evaluated in a scale ranging from 1 (poor)
to 4 (excellent)]. We calculated odds ratios (OR) by
univariate analysis, using Pearson’s chi-squared test to
compare frequencies of the outcomes at an alpha level of
0.05 and estimated their respective 95% CI.
We described the distribution of variables related to the
self-perception of body changes, including the moment
of perception, factors to which subjects attributed
changes, physician’s mention of changes, and medical
recommendations regarding the subject.
We carried out multivariate analysis using logistic
regression models for CFG and PFL, in order to identify
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variables independently associated with each of these
outcomes. We constructed models based on the
successive inclusion of independent variables whose P
values were below 0.25 in univariate analysis. Variables
independently associated with the outcome and those
shown to be confounding factors were kept in the final
model, considering plausibility and maximum likelihood
estimates during the modelling process.
Table 1. Distribution of subjects as to self-perception of body
changes, central fat gain, and peripheral fat loss and respective 95%
confidence intervals, São Paulo, Brazil, 2001.
Self-perception of body changes
Body changes
Central fat gain
Peripheral fat loss
Both CFG and PFL
N
%
95% CI
294
225
171
102
64.3
49.2
37.4
22.3
59.9–68.7
44.6–53.8
33.0–41.9
18.5–26.1
CFG, Central fat gain; CI, confidence interval; PFL, peripheral fat loss.
This study was ethically approved by the hospital
Institutional Review Board. Subject anonymity and
information confidentiality were ensured at all times.
2 years, whereas 43% had more than 5 years of diagnosis.
Most subjects (394/457, 86.2%) were receiving antiretroviral drugs, for periods ranging between 1 and 109
months (mean 37.3 months, median 38 months), and
prescriptions followed national guidelines for antiretroviral therapy [15].
Results
The study cohort comprised 457 individuals, with ages
ranging from 19 to 74 years (mean 38), 71.3% of whom
were men. Twenty-two per cent of patients reported
having been diagnosed as HIV infected for less than
Prevalence of self-perception of body changes
In the sample studied, 294 subjects reported selfperception of body changes. Of these, 171 perceived
Table 2. Univariate analysis of the association between sociodemographic and affective-related variables and self-perception of central fat gain
and peripheral fat loss in individuals with HIV/AIDS, São Paulo, Brazil, 2001.
CFG
Variable
Sex
Male
Female
Age (years)
< 30
30–45
> 45
Schooling (years)
8
9–11
> 11
Working
Yes
No
Income (reais)
499
500–1000
> 1000
Sexually active
Yes
No
Disclosed diagnosis to partner
Yes
No
Quality of relationship with partner
Very poor/poor
Regular
Good
Excellent
Quality of relationship with friends/family
Poor/regular
Good
Excellent
Quality of relationship with healthcare team
Poor/regular
Good
Excellent
n
Yes
OR
326
131
150
75
1
1.57
PFL
95% CI
P
n
Yes
OR
326
131
121
50
1
1.05
61
302
94
13
105
43
1
2.27
3.11
182
156
119
52
63
56
1
1.69
2.22
269
188
106
65
1
0.81
186
145
125
65
48
57
1
0.92
1.56
366
90
136
35
1
1.08
266
100
103
33
1
0.78
25
49
123
105
15
28
39
36
1
0.89
0.31
0.35
68
267
116
39
91
40
1
0.38
0.39
13
187
252
5
77
88
1
1.12
0.86
95% CI
0.03
1.04–2.36
0.83
0.69–1.59
0.68
61
302
94
29
153
43
1
1.13
0.93
182
156
119
75
79
71
1
1.46
2.11
269
188
131
94
1
1.05
0.65–1.96
0.49–1.77
0.006
1.18–4.37
1.49–6.49
0.007
0.95–2.25
1.32–3.38
0.003
1.08–2.67
1.37–3.60
0.78
0.73–1.53
0.29
0.55–1.20
0.66
186
145
125
87
75
62
1
1.22
1.12
366
90
171
54
1
1.71
0.79–1.88
0.71–1.76
0.08
0.58–1.46
0.98–2.48
0.05
1.07–2.73
0.71
0.67–1.73
0.11
266
100
131
40
1
0.69
0.43–1.10
0.31
0.48–1.27
0.07
25
49
123
105
22
40
71
64
1
0.75
0.38
0.49
68
267
116
37
133
53
1
0.83
0.7
13
187
252
9
100
114
1
0.51
0.37
0.28–2.02
0.16–0.94
0.20–1.21
0.02
0.33–2.37
0.13–0.75
0.14–0.85
0.51
0.48–1.42
0.39–1.29
0.001
0.22–0.66
0.21–0.72
0.08
0.15–1.72
0.11–1.22
P
0.41
0.35–3.55
0.27–2.70
CFG, Central fat gain; CI, confidence interval; OR, odds ratio; PFL, peripheral fat loss.
Table 3. Univariate analysis of the association between HIV/AIDS-related variables and self-perception of central fat gain and peripheral fat loss
in individuals with HIV/AIDS, São Paulo, Brazil, 2001.
CFG
Variable
Time since diagnosis (months)
0–24
25–60
> 60
Use of antiretroviral drugs
No
Yes
Duration of NRTI use (months)
0
1–18
19–36
37–60
> 60
Duration of stavudine use (months)
0
1–18
19–36
> 36
Duration of NNRTI use (months)
0
1–12
13–24
> 24
Duration of PI use (months)
0
1–18
19–36
> 36
Skipping doses of antiretroviral drug
No
Yes
n
Yes
OR
102
159
194
41
80
90
1
1.51
1.72
63
394
14
211
1
4.04
PFL
CI
P
n
Yes
OR
CI
102
159
194
21
57
92
1
2.16
3.48
63
394
10
161
1
3.66
62
67
81
151
93
12
14
29
68
48
1
1.1
2.32
3.41
4.44
242
69
100
46
73
26
50
22
1
1.4
2.32
2.12
0.80–2.45
1.43–3.73
1.11–4.03
231
96
95
34
80
32
44
15
1
1.4
2.32
2.12
0.80–2.45
1.43–3.74
1.12–4.03
173
56
102
126
52
16
42
61
1
0.93
1.94
2.4
122
272
43
118
1
1.41
0.09
0.91–2.43
1.06–2.80
< 0.001
1.21–3.85
1.99–6.07
< 0.001
2.16–7.55
< 0.001
1.81–7.41
< 0.001
62
67
81
151
93
15
35
41
87
47
1
3.43
3.21
4.26
3.2
242
69
100
46
109
43
51
22
1
2.02
1.27
1.12
1.17–3.49
0.80–2.03
0.59–2.10
231
96
95
34
105
50
53
16
1
1.3
1.5
1.07
0.81–2.10
0.94–2.45
0.52–2.19
173
56
102
126
70
35
59
61
1
2.45
2.02
1.38
122
272
66
145
1
0.97
1.61–7.28
1.55–6.64
2.19–8.28
1.57–6.51
< 0.001
0.46–2.61
1.07–5.05
1.68–6.92
2.10–9.41
0.09
0.34
0.002
0.16
0.006
1.32–4.56
1.23–3.32
0.86–2.19
0.005
0.48–1.81
0.98–2.72
1.36–3.52
0.88
0.63–1.49
P
0.13
0.90–2.19
CFG, Central fat gain; CI, confidence interval; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase
inhibitor; OR, odds ratio; PFL, peripheral fat loss; PI, protease inhibitor.
PFL and 225 CFG. We present the prevalence of study
outcomes and respective confidence intervals in Table 1.
Factors associated with self-perception of body
changes
Tables 2 and 3 present the results of the univariate analysis
of factors associated with self-perceived CFG and
PFL. The self-perception of both types of body changes
was directly associated with greater schooling and
antiretroviral drug use. Perceived body changes were
significantly associated with the duration of protease
inhibitor (PI) and nucleoside reverse transcriptase inhibitor use, but were not associated with the duration of
use of non-nucleoside reverse transcriptase inhibitors.
When stavudine use was evaluated alone, we detected an
association between the duration of use and self-perceived
PFL.
The self-perception of CFG was significantly more
frequent among women, whereas that of PFL was
significantly more frequent among older patients and
among patients with a longer time since diagnosis. The
quality of affective/social relationships with sexual
Table 4. Multivariate analysis using a logistic regression model for
investigating variables associated with self-perceived central fat gain
in individuals with HIV/AIDS, São Paulo, Brazil 2001.
CFG
Variable
Adjusted OR
Sex
Male
Female
Age (years)
< 30
30–45
> 45
Schooling (years)
8
9–11
< 11
Sexually active
Yes
No
Duration of PI use (months)
0
1–18
19–36
> 36
95% CI
1
1.84
1.17–2.91
1
1.07
0.72
0.58–1.95
0.35–1.49
1
1.48
2.68
0.93–2.36
1.61–4.46
1
1.82
1.08–3.06
1
2.41
2.31
1.43
1.26–4.61
1.36–3.91
0.86–2.36
CI, Confidence interval; CFG, central fat gain; OR, odds ratio; PI,
protease inhibitor.
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partners and with friends and family showed an inverse
association with self-perceived PFL; that is patients who
reported affective relationships of better quality were less
likely to perceive PFL.
Tables 4 and 5 present the logistic regression models
constructed in order to identify variables independently
associated with the self-perception of CFG and PFL,
respectively. Female sex was an independent predictor of
self-perceived CFG, as well as greater schooling and a
longer duration of PI use, whereas patients who reported
an active sexual life in the 12 months preceding the study
interview were less likely to perceive CFG. The selfperception of PFL was directly associated with older age,
greater schooling, longer duration of stavudine use, and
reported lack of adherence to antiretroviral treatment, and
was inversely associated with self-evaluated quality of
affective/social relationships with friends and family.
Of the 294 patients who perceived body changes, 277
provided additional information on the chronology of
this perception and the factors that, according to them,
could justify such changes. It is interesting to note that, of
these 277 patients, 190 (68.6%) reported perceiving body
changes after the use of antiretroviral drugs. Noteworthy
among the causes to which patients attributed these body
changes were antiretroviral drug use (59.9%), alterations
in eating habits (20.2%), and ageing (13.7%).
Concerning the attitude of the healthcare team in
response to patients’ body changes, 112 out of 457
Table 5. Multivariate analysis using a logistic regression model for
investigating variables associated with self-perceived peripheral fat
loss in individuals with HIV/AIDS, São Paulo, Brazil 2001.
PFL
Variable
Adjusted OR
Sex
Male
Female
Age (years)
< 30
30–45
> 45
Schooling (years)
8
9–11
< 11
Time of stavudine use (months)
0
1–18
19–36
> 36
Skip doses of antiretroviral therapy
No
Yes
Quality of relationship with friends/family
Poor/regular
Good
Excellent
95% CI
1
1.46
0.91–2.34
1
2.33
3.65
1.15–4.70
1.64–8.14
1
2.10
3.13
1.27–3.46
1.81–5.41
1
1.10
1.87
1.57
0.61–2.00
1.12–3.12
0.78–3.13
1
1.88
1.21–2.91
1
0.38
0.35
0.21–0.68
0.18–0.68
CI, Confidence interval; OR, odds ratio; PFL, peripheral fat loss.
subjects (24.5%) reported that their physician had
mentioned such changes, although only five subjects
reported their identification as ‘lipodystrophy’. In
contrast, 207 out of 457 subjects (45.3%) recalled having
received recommendations regarding these alterations.
For 114 of these patients, however, these recommendations were offered only after the patient had perceived the
changes and mentioned them to the healthcare professional. Patients reported more frequently having been
told to practice physical activities (188/207, 90.8%)
and to follow diets (177, 85.5%), and having been referred
to psychologists (168, 81.2%), psychiatrists (51, 24.6%),
cardiologists (97, 46.9%), or dieticians (84, 40.6%).
Changes in antiretroviral regimens were proposed to 88
patients (42.5%). Actual involvement in physical activities
was reported by 41% of interviewees and included mainly
walking, attending fitness gyms, swimming and cycling.
Discussion
In the present study we found a high prevalence of selfperceived body changes among 457 patients seen at a
university reference centre for the specialized treatment
of HIV/AIDS. Body changes were perceived by 64% of
subjects, including 49% who reported CFG and 37% who
reported PFL.
The prevalence of body changes among patients living
with HIV/AIDS reported in the literature shows great
variation, mostly as a result of the various case definitions
adopted by different researchers. Tien and Grunfeld [13],
in an analysis of a number of studies on the subject,
described that the mean prevalence of body changes
among these patients varied between 30 and 62%, ranging
from 18 to 45% for CFG and from 22 to 38% for PFL.
In the present study, the self-perception of all types of
body changes (CFG and PFL) was directly associated with
the use of antiretroviral drugs and with the duration of
nucleoside reverse transcriptase inhibitor and PI use. The
duration of PI use was independently associated with
the perception of CFG, and the duration of stavudine use
with the perception of PFL. The association between
body changes and HAART, especially with certain
antiretroviral regimens employed in clinical practice, has
been reported in a number of studies [11,12,14,16], based
either on the clinical diagnosis of lipodystrophy or on the
reported self-perception of body changes. It is currently
believed that lipodystrophy represents one of the most
important adverse events of therapy in the long-term
clinical management of individuals living with HIV/
AIDS. As analysis was carried out using each antiretroviral
drug class as an independent variable, potential interactions between concurrent or subsequent antiretroviral
regimens may have been overlooked in our study and
should be further investigated.
Self-perceived PFL was shown to be independently
associated with higher schooling and with adherence to
antiretroviral therapy. We believe the more frequent
perception of body changes and better adherence to
interventions among patients with higher schooling may
be a result of better access to information on treatment
and its implications. Nemes et al. [8], likewise, found a
significant association between schooling and the higher
prevalence of adherence to antiretroviral treatment in a
study that evaluated adherence to treatment in public
services. Patients with higher schooling are less likely
to suffer from social exclusion and stigma, which may
favour their recognition of body changes and their coping
with the transformations that take place in their bodies,
among other issues that affect individuals living with
HIV/AIDS.
It is interesting to note that subjects who admitted
‘skipping doses’ were more likely to perceive CFG. If, on
one hand, one may speculate that these individuals may,
from the psychosocial perspective, have elaborated issues
related to living with HIV/AIDS to a greater extent, so as
to admit lack of adherence to antiretroviral therapy and
the perception of body changes, on the other hand, we
cannot rule out the possibility that this lack of adherence
may have followed the perception of body changes, as
a reaction aimed at stopping the progression of these
disturbances. As a result of its cross-sectional design, the
present study does not allow us to evaluate the temporal
framework of this association. Ammassari et al. [17],
however, showed that individuals who perceive body
changes present lower rates of adherence with time.
In contrast, we found that self-evaluated quality of
affective relationships with the sexual partner and with
friends and family were inversely associated with the selfperception of PFL, the latter in an independent manner.
Therefore, subjects who reported good affective relationships were less likely to perceive body changes. Even
though limitations of a cross-sectional design in the study
preclude temporal conclusions concerning this association, we believe this finding is indicative of the importance of affective support for individuals living with
HIV when facing issues related to disease and treatment.
The value of social–affective networks has been highlighted in a qualitative study [9], which showed their
association with the self-perception of body changes. The
authors also observed less frequent perception by subjects
who received adequate affective support from sexual
partners.
A study with aims similar to ours, involving 904 subjects
under antiretroviral treatment recruited in 10 European
countries [16], found a 41% prevalence of self-perceived
CFG, 33% of self-perceived PFL, and 15% of both. The
authors identified as independent predictors of selfperception: therapy with PI, a longer time since diagnosis
and later stages of infection.
Interestingly, we found that the self-perception of body
changes differed depending on what type of change was
considered, which led us to the concept of body image.
Body image is understood as the representation of the
body’s subjective experience, resulting in a concept of
one’s self that reaches beyond the social and cultural
relational spheres [18,19]. It comprises two components:
the perceptive component, the object of the present
study, and the attitudinal component, related to affective,
cognitive, and behavioural issues regarding the body [20].
It is acknowledged that body image, as a construction
incorporating aspects of an individual’s living experience,
is determined by cultural and psychosocial factors, and is
markedly influenced by sex. Dissatisfaction with one’s
body, regardless of its form, is widespread among women,
reaching almost the status of a ‘normative discontent’
[21]. CFG is especially opposed to the socially constructed aesthetic ideals that value slimness, a trend that
has become more marked in the past few decades [19].
Women are particularly subject to an intense psychosocial
pressure to lose weight. Whereas men seem to regard their
bodies in terms of their active social, and therefore
functional role, women regard their bodies from an
essentially aesthetic viewpoint [22–25]. These considerations are in agreement with our finding of a significantly
greater perception of CFG among women. An additional
source of distress reported by female patients in our
cohort was that CFG is often mistaken for pregnancy, a
condition that, even though frequently desired by women
living with HIV, is often interpreted as problematical.
The perception of PFL, on the other hand, was significantly more frequent among older subjects, and may
reflect concerns with body marks, culturally identified as
signs of ageing. In particular, lipoatrophy, which includes
the loss of facial adiposity, in light of its greater visibility to
outside observers, was significantly more frequent among
patients who reported less affective support from friends
and family.
It is important to point out that our aim in the present
project was to evaluate the self-perception of body
changes. Discrepancies between self-perception and the
clinical identification of these changes have seldom been
explored in individuals living with HIV/AIDS [26].
However, they have been extensively evaluated in the
literature on obesity and eating disorders. Donath [27],
for example, showed in a population-based survey that
women were more likely to see themselves as overweight
compared with men.
Evaluating this difference in perception and knowing
how to include the patient’s self-perception in the planning and management of prophylactic or therapeutic
interventions is essential in order to ensure the efficiency
of these measures, both at the individual level, in clinical
medicine, and from the public health perspective. Only
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taking this into account will the healthcare team succeed
in offering patients parameters on how to deal with the
expectations and limitations of any intervention [28].
From the perspective of comprehensive care, directed
not only towards physical well-being, but also towards
greater satisfaction in the psychosocial realm, healthcare
professionals must remain attentive to the effects of
lipodystrophy-related body changes and to the way
individuals living with HIV/AIDS perceive and deal with
these changes. The impact of these changes, in the form
of stigma and prejudice, is harmful to self-esteem and may
lead to severe forms of psychological distress, including
fear, emotional dependence, feelings of loneliness,
isolation, and depression [6,9]. Facial lipoatrophy, as a
result of its being easily identified by others, is becoming a
marker of HIV seropositivity among the gay community,
being termed the ‘Kaposi’s sarcoma of the twenty-first
century’ [9]. If, in the first stage of the epidemic, the
image of AIDS was characterized by body changes
attributed to the disease (the social representation of
AIDS), we nowadays face once again the possibility of
stigma based on the body changes (CFG and PFL) related
to the treatment itself.
Our patients’ reports point towards a medical attitude that
avoids naming body changes. We verified, however, that
even though reference to these changes is frequently
omitted, a significant share of these patients received
medical recommendations on the subject or were referred
to other professionals, especially after having mentioned
these changes to their physicians. Similar medical interventions were reported in a qualitative study of patients
from an STD/AIDS clinic in London [9]. The subjects of
that study reported reluctance in addressing the issue
with their physicians, considering it a ‘waste’ of the
professional’s time. However, once the initial difficulty
was overcome, patients realized that their physicians
listened to and seriously considered their fears.
Recognizing the self-perception of body changes in
individuals living with HIV/AIDS and its determinants
may prove extremely useful in improving the care provided to these patients. Once the fear of imminent death
is overcome by the use of HAART, individuals living
with HIV/AIDS seek to expand their horizons, which
includes establishing new affective relationships, raising a
family, and renewing professional projects. To this end, it
is the task of healthcare professionals to find room for the
discussion of body changes that may appear as a side-effect
of antiretroviral treatment. Listening to people’s longings
and desires, their fears and anxieties with respect to
treatment, as well as other issues concerning living with
HIV (sexuality, disclosure of diagnosis), and including the
patient in therapeutic decisions in this regard will most
certainly improve the care provided, contributing towards
greater adherence to proposed interventions and towards
improvements in quality of life.
Acknowledgements
The authors would like to thank the psychologists Érika
T. Eid and Luciene Maester for their collaboration during
the first stage of the study and the multiprofessional team
of the Casa da AIDS for their support. They also wish to
thank their colleagues from the seminar, sponsored by the
National STD/AIDS Program of the Ministry of Health,
for the valuable suggestions provided while reviewing the
manuscript.
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A syndrome of peripheral lipodystrophy, hyperlipidaemia and
insulin resistance in patients receiving HIV protease inhibitors.
AIDS 1998; 12:F51–F58.
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14. Carter VM, Hoy JF, Bailey M, Colman PG, Nyulasi I, Mijch AM.
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for HIV-infected adults and adolescents 2004. Available at:
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Florence E, et al. Self-reported signs of lipodystrophy by persons
living with HIV infection. Int J STD AIDS 2002; 13:393–398.
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S21
Survival of AIDS patients using two case definitions,
Rio de Janeiro, Brazil, 1986–2003
Dayse Pereira Camposa, Sayonara Rocha Ribeiroe, Beatriz Grinsztejna,
Valdiléa G. Velosoa, Joaquim Gonçalves Valenteb,
Francisco Inácio Bastosc, Mariza Gonçalves Morgadod and
Angela Jourdan Gadelhab
Background: Recent studies have shown substantial increases in the survival of AIDS
patients in developed countries and in Brazil as a result of antiretroviral therapy (ART)
and prophylaxis for opportunistic infections. This study compares survival rates using
the Brazilian Ministry of Health 2004 and Centers for Disease Control and Prevention
(CDC) 1993 case definitions in a large HIV/AIDS referral centre in Rio de Janeiro.
Methods: Survival after AIDS diagnosis was assessed in a clinic-based cohort of 1415
individuals using the Kaplan–Meier method and Cox proportional hazards models.
Results: There were 393 (88%) deaths from AIDS-related causes and 52 (12%) from
unrelated or unknown causes. A total of 205 patients (14%) were lost to follow-up and
765 patients (55%) remained alive until the end of the study. Three-quarters of patients
(75%) were still alive 22 months [95% confidence interval (CI) 19–26] after the AIDS
diagnosis according to the CDC case definition and 31 months (95% CI 26–36)
according to the Ministry of Health case definition. Independent predictors of survival
included AIDS defined by CD4 cell count and any use of highly active antiretroviral
therapy, with either case definition, and initial stage of the case, with the Ministry of
Health case definition.
Conclusion: Survival observed in this reference centre is comparable or longer than
other international studies, although the choice of case definition criterion influenced
findings. Adoption of the Ministry of Health case definition may enhance the ability to
track the use of and outcomes from ART among AIDS patients.
AIDS 2005, 19 (suppl 4):S22–S26
Keywords: AIDS, Brazil, case definition, highly active antiretroviral therapy,
survival
Introduction
Recent studies have shown that the survival of patients
with AIDS in Brazil has been increasing substantially,
as observed in developed countries, mainly as a result
of the universal access to antiretroviral therapy (ART)
[1–4].
Several criteria have been used to define AIDS. Brazil
initially used the case definition established by the Centers
for Disease Control and Prevention (CDC) USA, but
later adopted its own case definition, which combines an
assessment of clinical conditions, the presence or absence
of defining diseases and immunological status [5]. In
accordance with Brazil’s revised case definition, Brazilian
From the aEvandro Chagas Clinical Research Institute, bNational School of Public Health, cScience and Technology Information
Center, and dOswaldo Cruz Institute, Oswaldo Cruz Foundation and the eMunicipal Health Department of Rio de Janeiro, STD/
AIDS Program, Rio de Janeiro, Brazil.
Correspondence to Dayse Pereira Campos, Av. Brasil, 4365, 21045-900, Rio de Janeiro, RJ, Brazil.
S22
Survival in AIDS in Rio de Janeiro, Brazil Campos et al.
Ministry of Health 2004, an AIDS case can be defined by
a CD4 cell count below 350 cells/ml, a level that corresponds to a status at which ART may be considered.
Most study patients have adopted the CDC case
definition [6], but considering Brazil’s unique position
as a developing country with more than 135 000 patients
under ART [7], it becomes relevant to analyse the survival
of these patients using both a case definition that enables
comparisons with international studies and one adapted
to Brazil’s specific conditions. The present study makes
such a comparison in a referral unit within a large
biomedical research centre, the Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro.
Methods
A cohort of AIDS patients was followed at the Evandro
Chagas Clinical Research Institute (IPEC–FIOCRUZ)
between 1986 and 2002. Cases, defined by either the
CDC or Ministry of Health definitions, which progressed
to AIDS by 31 December 2003, were considered for the
present analysis. Individuals less than 13 years of age or
with less than 15 days of follow-up were excluded from
the analysis.
The outcome studied was death from an AIDS-related
cause. Survival was calculated as the time elapsed from the
date of AIDS diagnosis until the data of death or the last
attendance. Deaths from causes unrelated to AIDS, cases
with loss of follow-up, and individuals who stayed alive
until the end of the study period were censored at the last
date documented to be alive.
The following covariates were considered: sex; education
level; age at AIDS diagnosis; exposure category [8]; initial
stage of disease; prophylaxis for opportunistic infections;
initial and last ART; and the period when the diagnosis
was made. The clinical stage of disease at the first visit was
classified as AIDS and non-AIDS. For individuals who
presented with more than one defining condition, a
hierarchy was established such that the immunological
status had primacy over the defining disease, and disease
over the Ministry of Health scoring.
ART use was categorized as: monotherapy; combined
therapy, when two or more nucleoside reverse transcriptase inhibitors were used; and highly active antiretroviral
therapy (HAART), when at least one non-nucleoside
reverse transcriptase inhibitor or protease inhibitor was
used. The category ‘without therapy’ comprised those
who died or were lost to follow-up before 1990, had no
indication for therapy, or refused treatment. The period
of diagnosis was categorized in relation to when
antiretroviral drugs and HAART therapy were first
available: up to 1990 (before ART), 1991–1995 (mono/
double therapy), and from 1996 onwards (HAART).
The survival functions were described and compared
using the probabilities of survival for 1 and 5 years after
AIDS diagnosis, using the Kaplan–Meier method and the
log rank test [9]. The Wald test was used to define the
variables to be entered into the Cox model. The stepwise
method was used to fit the model, assessing the maximum
likelihood in each step [10].
Results
Subjects included 1415 cases diagnosed up to 31
December 2003. Of these, 445 patients (31%) died,
205 (14%) were lost of follow-up, and 765 (55%) were
alive as of the end of the study. Of the cases that progressed
to death, 393 (88%) were AIDS-related and 52 (12%)
were from unrelated or unknown causes. The mean age at
the baseline was 35 years. There were 468 female cases in
the study (33%). The majority of the patients had less than
8 years of education.
The Ministry of Health case definition identified 289
cases that did not meet the CDC criteria. The opposite
happened in only 16 cases.
Three-quarters of patients (75%) were still alive 22
months [95% confidence interval (CI) 19–26] after AIDS
diagnosis according to the CDC case definition and 31
months (95% CI 26–36) according to the Ministry of
Health case definition. Because the vast majority of AIDS
patients were still alive at the study end, it was not possible
to estimate the median length of survival using either case
definition (Fig. 1).
In bivariate analysis, using either case definition: female
sex; absence of baseline clinical syndrome; AIDS case
definition via immunological status; prophylaxis for
tuberculosis, pneumocystosis and toxoplasmosis; any
use of HAART; and diagnosis after 1995 were predictors
of longer survival.
In multivariate analysis, the absence of a baseline clinical
syndrome and any use of HAART were predictors of
longer survival for both case definitions. For the Ministry
of Health criteria, the initial stage of the case was also
identified as a predictor of longer survival (Table 1).
Discussion
The study highlights a substantial increase in survival after
the introduction of HAART. Among international
studies, the greatest survival encountered in recent years
S23
Survival Functions
MS 2004
Survival Functions
CDC 1993
1.2
1.2
1.0
1.0
Cumulated Survival
Cumulated Survival
S24
0.8
0.6
0.4
0.2
0.8
0.6
0.4
0.2
0.0
−25 0
25
50
75
100 125 150 175 200
Months of survival
0.0
−25 0
25
50
75 100 125 150 175 200
Months of survival
Fig. 1. Survival function for the AIDS cases according to Centers for Disease Control and Prevention 1993 and Brazilian
Ministry of Health 2004 case definitions for period of diagnosis. Evandro Chagas Clinical Research Institute. Rio de Janeiro,
) 1996 and onwards,
Brazil, 1986–2003. CDC, Centers for Disease Control and Prevention; MS, Brazilian Ministry of Health. (
(
) 1991 to 1995, (
) up to 1990.
comes from the study by Dore et al. [11], in Australia,
with cases defined between 1993 and 2000, using the
CDC case definition. For patients diagnosed in 1993/
1995, the median survival was estimated as 20 months and
40 months for the period 1996/2000. Our findings
compare favourably.
Recent studies [2,3] have already given evidence of a
substantial increase in the estimated survival of individuals
living with AIDS in Brazil. However, comparing the two
definitions, longer survival was shown by the Ministry
of Health than by the CDC criteria. These findings may
be explained, partly, by using a CD4 cell cut-off of
350 cells/ml in the Ministry of Health case definition
rather than 200 cells/ml, as in the CDC case definition.
The absence of a baseline clinical syndrome and any use of
HAART were shown to be associated with a greater
probability of survival for both case definitions, but the
initial stage of the case was found to be associated with
survival only when the Ministry of Health case definition
was considered.
We believe that the longer survival found in the present
study, in relation to previous Brazilian studies, is mainly
caused by the continuous improvement in the types
and delivery of treatment. We also believe that the
longer survival is partly the result of the excellence of care
at the study institution. On the other hand, the findings
do not seem to be associated with the initiation of
antiretroviral drugs at earlier stages of immunodepression.
Recent studies suggest that initiating ART at this level
does not impact survival [12] as much as the effective
use of antiretroviral drugs. Unfortunately, the study did
not appraise antiretroviral adherence.
In the present study, the longer survival initially found
for women did not remain significant in the multivariate analysis. The apparent improved survival may have
been confounded by the increase in the numbers of
cases among women in recent years, when the use of
combined therapy or HAART and prophylaxis for
opportunistic infections came into common use. Similar
results were found in a study conducted in the USA in
2001 [4].
For both criteria utilized, the defining condition for
AIDS determined significant differences in survival, with
longer survival for cases defined by immunological status.
Corroborating other studies [4,12,13], the present results
suggest that early follow-up, with cases defined by
immunological status rather than disease allows for the
timely identification of indications to initiate therapies
and prophylaxis and therefore longer survival.
Survival was significantly greater for patients who had had
prophylaxis for Pneumocystis jirovecii pneumonia, tuberculosis and toxoplasmosis for both case definitions. Similar
results have been found in other studies conducted in
Brazil that evaluated prophylaxis for Pneumocystis jiroveciii
pneumonia [3,14–16].
We observed a temporal increase in survival over time in
bivariate analysis. Compared with the period after 1996,
the risk of death was more than ninefold for cases
diagnosed up to 1990, and fourfold for the period 1991–
1999, for both case definitions. These results agree with
those of other authors [3,4,11,17–19]. The period of
diagnosis was not included in the final multivariate model
because of its collinearity with the treatment using
antiretroviral drugs.
Survival in AIDS in Rio de Janeiro, Brazil Campos et al.
Table 1. Absolute frequency, description of the survival function, unadjusted and adjusted hazard ratio for the co-factors considered for AIDS
patients, defined by the Centers for Disease Control and Prevention 1993 and Brazilian Ministry of Health 2004 criteria. Evandro Chagas Clinical
Research Institute. Rio de Janeiro, Brazil. 1986–2003.
Cases
1 year
Variable
Cohort
Sex
Female
Male
Age at time of diagnosis
Less than 35 years
35 years or over
Education
Up to 8 years
9 or more years
Category of exposure
Blood
Sexual
Initial classification
Non-AIDSa
AIDS
Case definition
Immunological statusa
AIDS-defining disease
Scoring
Recommended prophylaxis
Tuberculosis
Administered
Not administered
PCP
Administered
Not administered
Toxoplasmosis
Administered
Not administered
Initial antiretroviral therapy
No therapy
Monotherapy
Combined
HAART
Last antiretroviral therapy
No therapy
Monotherapy
Combined
HAARTa
Period of diagnosis
Up to 1990
1991–1995
1996 and onwards
Unadjusted hazard
ratio
Probability
Adjusted hazard ratio (95% CI)
5 years
CDC
n
MS
n
CDC
MS
CDC
MS
1126
1399
0.82
0.85
0.61
0.67
344
782
465
934
0.84
0.81
0.88
0.84
0.70
0.57
0.76
0.62
529
597
686
713
0.82
0.81
0.86
0.85
0.60
0.62
0.67
0.67
615
470
735
618
0.80
0.86
0.83
0.89
0.61
0.63
0.66
0.70
95
770
112
964
0.78
0.81
0.79
0.86
0.61
0.59
0.61
0.66
552
574
831
568
0.85
0.79
0.90
0.78
0.65
0.57
0.74
0.57
601
525
–
895
300
204
0.93
0.69
0.97
0.76
0.59
0.73
0.47
0.82
0.5
0.40
146
51
190
64
0.76
0.71
0.81
0.75
0.56
–
0.65
–
716
174
894
214
0.85
0.79
0.88
0.83
0.64
0.57
0.7
0.63
471
90
589
109
0.85
0.77
0.87
0.83
0.64
0.60
0.69
0.67
210
414
183
319
268
489
258
384
0.39
0.84
0.96
0.95
0.42
0.89
0.97
0.96
0.08
0.51
0.85
0.85
0.13
0.59
0.89
0.88
210
154
72
690
268
168
109
854
0.39
0.65
0.79
0.97
0.42
0.70
0.89
0.98
0.06
0.05
0.26
0.87
0.13
0.62
0.49
0.90
142
356
628
181
438
780
0.51
0.73
0.93
0.54
0.79
0.95
0.14
0.41
0.84
0.21
0.50
0.86
CDC
MS
P < 0.00
1.00
1.45
P > 0.30
1.00
0.95
P >0.13
1.17
1.00
P >0.40
0.99
1.00
P < 0.02
1.00
1.37
P < 0.00
1.00
2.53
–
P < 0.00
1.00
1.62
P > 0.50
1.00
1.06
P >0.21
1.26
1.00
P >0.25
1.20
1.00
P < 0.00
1.00
1.96
P < 0.00
1.00
3.87
4.63
P >0.30
1.00
1.00
P < 0.02
1.00
1.36
P < 0.03
1.00
1.48
P < 0.00
17.60
4.60
1.23
1.00
P < 0.00
19.78
15.54
6.93
1.00
P < 0.00
9.67
4.56
1.00
P >0.30
1.00
1.00
P < 0.03
1.00
1.34
P < 0.01
1.00
1.55
P < 0.00
18.45
4.47
1.10
1.00
P < 0.00
21.20
18.11
4.95
1.00
P < 0.00
10.15
4.65
1.00
CDC
MS
1.00
1.83 (1.10–3.06)
1.00
2.09 (1.26–3.48)
1.00
2.03 (1.14–2.63)
1.60 (0.79–3.26)
18.40 (10.15–33.20)
9.03 (4.54–17.65)
1.00
18.88 (10.34–34.45)
6.40 (3.20–12.80)
1.00
CDC, Centers for Disease Control and Prevention; CI, confidence interval; HAART, highly active antiretroviral therapy; MS, Brazilian Ministry of
Health; PCP, Pneumocystis jirouecii pneumonia;
Reference category.
a
Our study did not examine survival from HIV diagnosis
on. Survival expectations from this point should be longer
because the use of treatment before diagnosis is likely to
lengthen the time to AIDS. However, AIDS achieved
after the initiation of treatment may be associated with
severe immunosuppression and treatment failure and
therefore shortened survival time after AIDS. Our study
population may not be typical of other areas of Brazil. To
the extent that a higher quality of care may be delivered to
this population, survival may better than elsewhere.
The present findings reinforce the importance of
stimulating qualified medical assistance at an early
stage, with the utilization of antiretroviral and prophylactic therapy and close monitoring. It is also important
to emphasize that the choice of criteria for case
definition directly impacts on the results obtained. The
simultaneous use of the CDC and Ministry of Health
case definitions provided evidence of distinct survival
lengths and allowed comparisons with international
studies.
S25
S26
Acknowledgements
The authors would like to thank Willi McFarland for his
comments on a previous version of this manuscript, and
Keyla Marzochi, Richard Moore, Luiz Alberto Matzenbacher, Claudio Vieira Lisboa, Eliane Berinqué Braga,
Evilim Jashar, Kátia Valente, Cláudia Codeço, Carolina
Bandeira, Dayvison Francis Freitas, Alzeny Gusmão
Macedo, Ione Nascentes, Tiago de Souza Bandeira,
Bruno Castelo Branco, Tatiana Nascimento, Márcio
Jablonka, Renato de Noronha da Cunha, and Ieda
Ramos.
Sponsorship: This study was funded by STD/AIDS
Coordination Office, Ministry of Health (project no.
914/BRA/59, UNESCO, FENSPTEC no. 99047).
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Characteristics and survival of AIDS patients
with hepatitis C: the Brazilian National Cohort of
1995–1996
José Ricardo Pio Marinsa,b, Marilisa Berti de Azevedo Barrosa,
Helymar Machadoa, Sanny Chenc, Leda Fátima Jamald and
Norman Hearste
Background: As AIDS patients live longer, the management of co-morbidities becomes
increasingly important. Previous studies from developed countries give conflicting
results as to whether co-infection with hepatitis C virus (HCV) lowers the life expectancy
of individuals with AIDS.
Methods: This retrospective cohort study was based on a medical record review of a
nationally representative sample of 2821 adult AIDS cases diagnosed in 1995 and 1996
in Brazil. We compared the characteristics and survival of patients known to be positive
and negative for HCV.
Results: A total of 833 patients received HCV testing, and the prevalence was 33%.
HCV-positive patients received less intensive antiretroviral treatment. The crude
mortality was greater for HCV-positive patients (hazard ratio 1.26; P ¼ 0.04), but
HCV status was not a significant predictor in a multivariate analysis that included
other predictors of survival.
Conclusion: Brazilian AIDS patients with hepatitis C have a shorter survival than those
without, but this seems to be mainly as a result of their receiving less antiretroviral
treatment. We cannot say whether this is because of the fear of hepatotoxicity, an
inability to tolerate treatment, or for other reasons. To improve survival, these patients
need optimal treatment of their HIV disease.
AIDS 2005, 19 (suppl 4):S27–S30
Keywords: AIDS, Brazil, hepatitis C, HIV, injecting drug use, survival
Introduction
Highly active antiretroviral therapy (HAART) transformed the management and life expectancy of AIDS
patients, with dramatic increases in survival in rich
countries [1–4]. In Brazil, the first developing country to
provide universal free access to HAART, the median
survival increased from 5 months in 1982–1989 [5] to 58
months among cases diagnosed in 1996 [6]. These
advances have led to new challenges, including the
management of co-morbidities such as chronic viral
hepatitides, which now have a greater potential for
expression in individuals with AIDS [7]. Hepatitis C virus
(HCV) has been especially important in AIDS patients as
a result of its efficient transmission among injecting drug
users [7,8] with prevalences reaching 50–90% [9,10], and
the high proportion of infections (55–85%) that become
chronic. Various studies published in the 1990s showed
that AIDS-related immunosuppression increases HCV
viral replication and hepatic inflammation, accelerates
fibrosis, and adds to the risk of cirrhosis and hepatic failure
[11,12].
From the aUniversidade Estadual de Campinas, Campinas, the bPrograma Nacional de DST/AIDS, Brası́lia, DF, Brazil, the cJohns
Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA, and the dCoordenação Estadual de DST/Aids de São
Paulo, São Paulo, Brazil and the eUniversity of California, San Francisco, California, USA.
Correspondence to José Ricardo Pio Marins, MD, PhD, Ministério da Saúde-Programa Nacional de DST/AIDS, Av. W3 Norte,
SEPN 511, bloco C, COD-70750-00, Brası́lia, DF, Brazil.
Tel/fax: +55 61 4488005; e-mail: [email protected]
S27
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Whereas HIVappears to affect the natural history of HCV
infection, the converse is less certain. In the pre-HAART
era, studies in the USA, France, and Italy found no
differences in survival between AIDS patients with and
without HCV [11,13,14], whereas a study in Germany
did find a shorter survival among co-infected patients
[15]. In the post-HAART era, studies in Switzerland and
Canada found decreased survival among AIDS patients
with HCV [16,17], whereas studies in the USA and
Australia did not [7,18]. No previous studies have
examined this question in Brazil or elsewhere in the
developing world. We therefore undertook an analysis of
the Brazilian National Survival Cohort of 1995–1996 to
characterize Brazilian AIDS patients co-infected with
hepatitis C and to determine whether their survival differs
from that of AIDS patients without hepatitis C.
Methods
This was a retrospective cohort study of a representative
sample of 2821 of the 40 587 adult AIDS patients
reported in Brazil in 1995 and 1996. Details of the
methods, including sampling strategy, data collection,
AIDS diagnostic criteria, death ascertainment, and date of
censor for survival analysis have been described previously
[6]. In brief, this was a medical record study in which
trained abstracters collected data between April 2000 and
January 2002. The variables analysed included demographics (sex, age, educational level), transmission
category, AIDS diagnostic criterion, symptoms and
opportunistic infections at diagnosis, type of antiretroviral
treatment received, and serology for hepatitis B and C.
The presence of HCV was determined by standard
enzyme-linked immunosorbent assay serology; confirmatory testing was not generally available in Brazil at the
time of this study. Hepatitis B infection was determined
by the presence of hepatitis B surface antigen. Neither
hepatitis B nor hepatitis C serology were part of the
routine care for AIDS patients in Brazil, and we did not
attempt to ascertain physicians’ reasons for ordering or
not ordering these tests. Patients were included in the
survival analysis if their medical record indicated HCV
testing at any time.
To examine bivariate associations, we used the chi
squared or, when appropriate, Fisher’s exact tests. We
used the Kaplan–Meier procedure to generate survival
curves and the log-rank test to compare these. Cox
regression was used to estimate hazard ratios (HR) and
determine significant (P < 0.05) predictors of survival.
This study was approved by the Research Ethics
Committee of the São Paulo State AIDS Program.
Results
Of 2821 cases studied, 29.5% (833) had HCV testing, a
figure that varied little by sex or age (Table 1). The
proportion tested varied by region, from 38.1% in the
Table 1. Demographic characteristics of hepatitis C virus-infected AIDS patients, Brazil, 1995–1996.
Characteristics
Sex
Male
Female
Total
Agea (years)
< 25
25–34
35
Total
Regiona
South
South-east
North-east/north/central east
Total
Educationa
Primary incomplete
Primary/not secondary complete
Secondary complete
Superior
Total
Transmission categorya
Homo/bisexual
Heterosexual
Injection drug user
Transfusion
Total
Total
No. tested
%
2058
763
2821
597
236
833
29.0
30.9
29.5
312
1273
1227
2821
97
385
346
828
31.0
30.2
28.2
29.4
454
1872
457
2821
101
714
9
824
22.2
38.1
1.9
29.5
1029
484
243
250
2006
330
132
55
57
574
32.0
27.2
22.6
22.9
28.6
631
999
674
74
2378
168
314
254
16
752
26.6
31.4
37.6
21.6
31.6
P
HCVþ
% Prevalence
PR
95% CI
1.20–1.97
–
37.1
24.1
33.4
1.54
1
0.320
222
57
279
32.9
37.4
29.4
33.5
1.12
1.27
1
0.424
32
144
102
278
34.6
33.7
22.2
1.56
1.52
1
< 0.001
35
241
2
278
38.7
31.0
23.6
14.0
33.1
2.76
2.21
1.68
1
0.002
128
41
13
8
190
8.3
18.1
71.2
18.7
33.9
1
2.18
8.55
2.25
< 0.001
14
57
181
3
255
P
< 0.001
0.81–1.55
1.03–1.56
–
0.076
0.45–5.45
0.45–5.18
0.751
1.43–5.33
1.11–4.42
0.76–3.74
–
< 0.001
–
1.25–3.79
5.15–14.21
0.72–7.01
0.001
CI, Confidence interval; HCVþ, hepatitis C virus positive; PR, prevalence rate.
a
Totals vary because of missing observations.
Hepatitis C in Brazilian AIDS patients Marins et al.
south-east to only 1.9% in the less developed regions of
the country. Patients with lower educational levels were
more likely to be tested as were injecting drug users.
Among those tested, prevalence was 33.4%, and this
varied greatly by subgroup. Prevalence was 1.54 times
higher for men than women and 2.76 times higher in
the least educated subgroup than the most educated.
Prevalence ranged from 8.3% in the homo/bisexual
group to 71.2% among injecting drug users.
We found few significant differences in clinical presentation, although fever, fatigue and anaemia were more
common in patients with HCV (prevalence ratios 1.39,
1.26, and 1.24, respectively; P < 0.05). Patients with
HCV were twice as likely (13.9 versus 6.7%) to be
positive for hepatitis B surface antigen (P ¼ 0.002). They
received significantly less antiretroviral treatment. Of the
HCV-positive patients, 40% received triple therapy, 40%
received single or double therapy, and 20% received no
antiretroviral treatment. For HCV-negative patients,
these numbers were 55, 30, and 15%, respectively
(P ¼ 0.001).
Figure 1 shows survival curves for patients with and
without HCV. In bivariate analysis, survival was shorter
for patients with HCV (HR of death 1.26; P ¼ 0.044).
This difference was greatest among men (HR 1.40;
P ¼ 0.01), ages 25–34 years (HR 1.69; P ¼ 0.001) and
those with CD4 cell counts greater than 200 (HR 2.59;
P ¼ 0.01). There was a trend towards a higher HR for
cases diagnosed in 1996 versus those diagnosed in 1995
(HR 1.34 versus 1.12; P ¼ 0.06).
In multivariate analysis, the type of antiretroviral
treatment was by far the strongest predictor of survival
(HR 16.8 for none versus triple and 5.9 for single/double
versus triple therapy; P < 0.0001). After adjusting for
antiretroviral treatment and the severity of illness at the
time of the AIDS diagnosis (HR 1.81 for severely ill
versus mildly/moderately ill; P < 0.0001), the HR for
1.0
Cumulative survival
0.8
Hepatitis C −
0.6
0.4
Hepatitis C +
0.2
0.0
0
20
40
60
80
100
Months
Fig. 1. Cumulative survival of AIDS patients with and without hepatitis C.
being HCV positive was 0.94 (95% confidence interval
0.75–1.18; P ¼ 0.59).
Discussion
In this study, Brazilian AIDS patients co-infected with
hepatitis C had crude mortality 26% higher than those not
co-infected, a difference that disappeared after adjusting
for confounders. This difference was mainly limited to
men, to ages 25–34 years, and to those with CD4 cell
counts greater than 200 cells/ml. But post-hoc subgroup
analyses such as these should be interpreted with great
caution. Perhaps more important is our finding that
hepatitis C status was not a significant predictor of
survival in multivariate analysis. The higher mortality
may thus be primarily because those with hepatitis C are
less likely to receive intensive antiretroviral treatment.
Less intensive treatment may be because of the knowledge
of treating physicians that HAART is potentially
hepatotoxic [1], the inability of patients with liver disease
to tolerate more intensive antiretroviral treatment
regimens, or physicians’ beliefs that injecting drug users
cannot adhere to treatment. Less intensive antiretroviral
treatment for injecting drug users has been reported in
some [16,18] but not all [17] studies of AIDS patients
elsewhere.
Our results match those of many studies in both the preHAART [15,19] and the post-HAART [7,18] eras in
which hepatitis C status was not an independent predictor
of survival. Other studies in the post-HAART era,
however, have found poorer survival in co-infected
patients even after adjusting for confounders [16,17]. It is
possible that hepatitis C may be having more of an impact
on survival now that AIDS patients are living longer.
Alternatively, it is possible that residual confounding
between hepatitis C status and other predictors of
survival, especially optimal antiretroviral treatment,
produces more notable differences in survival now that
treatment is better. Either of these possibilities is
consistent with our finding of a trend towards a greater
difference in survival for Brazilian patients diagnosed in
1996 (when HAARTwas becoming available and survival
was substantially longer) than in patients diagnosed in
1995.
Only 29.5% of our patients were tested for hepatitis C.
Such testing was at the discretion of the treating
physicians, and the likelihood varied by patient characteristics. Undoubtedly, many other patients with hepatitis
C were never tested. Others, particularly haemophiliac
patients, may have been tested in sites other than the HIV
care facilities for which we reviewed their records. This
might explain the surprisingly low level of testing
observed in the blood product transmission category.
We compared patients who were known to be positive
S29
S30
with those known to be negative; no one was assumed to
be negative because of a lack of testing. Our results should
therefore be internally valid among patients tested. But
we cannot say whether the results would have been
different if more patients had received hepatitis C testing.
As our data started at AIDS diagnosis, we also cannot say
whether hepatitis C co-infection might affect the time of
progression from HIV infection to AIDS. Another
weakness of this study is that we did not have information
on whether the cause of death was related to liver disease.
Whether co-infected patients have higher mortality
because of their hepatitis C status per se or because they
receive less antiretroviral treatment, our findings and
those of others suggest they are a group at higher risk that
deserves special attention. Although concerns regarding
the hepatotoxicity of drugs, adherence, and ability to
tolerate treatment are real, these must be balanced against
growing evidence that antiretroviral treatment may
protect against HCV-related liver disease [20]. Recent
reports have emphasized the importance of the optimal
treatment of hepatitis C in co-infected patients [21], but
the optimal treatment of their HIV disease is no less
important. Only by providing both can we hope to meet
the needs of these patients and close the gap in survival.
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Schechter MT, Montaner JSG. Improved survival among HIVinfected individuals following initiation of antiretroviral therapy. JAMA 1998; 279:450–454.
2. Lee LM, Karon JM, Selik R, Neal JJ, Fleming PG. Survival after
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era, United States, 1984–1997. JAMA 2001; 285:1308–
1315.
3. Pezzoti P, Napoli PA, Acciai S, Boros S, Urciuoli R, Lazzeri V,
Rezza G. Increasing survival time after AIDS in Italy: the role of
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4. Li Y, McDonald AM, Dore GJ, Kaldor JM. Improving survival
following AIDS in Australia. AIDS 2000; 14:2349–2354.
5. Chequer P, Hearst N, Hudes ES, Castilho EA, Rutherford G,
Loures L, et al. Determinants of survival among adult Brazilian
AIDS patients, 1982–1989. AIDS 1992; 6:483–487.
6. Marins JRP, Jamal LF, Chen SY, Barros MBA, Hudes ES, Barbosa
7. Lincoln D, Petoumenos K, Dore GJ. HIV/HBV and HIV/HCV
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8. Des Jarlais DC, Diaz T, Perlis T, Vlahov D, CAREY M, Mary L,
et al. Variability in the incidence of human immunodeficiency
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2003; 157:467–471.
9. Mohsen AH, Easterbrook P. Hepatitis C testing in HIV infected
patients. Sex Transm Infect 2003; 79:76.
10. Estrada A. Epidemiology of HIV/AIDS, hepatitis B, hepatitis C,
and tuberculosis among minority injection drug users. Oxford J
Public Health Rep 2002; 17 (Suppl. 1):S126–S134.
11. Wright TL, Hollander H, Pu X, Held MJ, Lipson P, Quan S, et al.
Hepatitis C in HIV-infected patients with and without AIDS:
prevalence and relationship to patients survival. Hepatology
1994; 20:1152–1155.
12. Gonzales SA, Talal AH. Hepatitis C virus in human immunodeficiency virus-infected individuals: an emerging comorbidity
with significant implications. Semin Liver Dis 2003; 23:149–
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13. Chaillon S, Berthelo TP, Pozzetto B, Frézard A, Pegue-Lafeuille
H, Beytout J, et al. Etude pronostique comparative d’une
population SIDA en fonction du statut sérologique VHC. Presse
Med 1999; 28:1101–1104.
14. Dorucci M, Pezzoti P, Phillips NA, Lepri CA, Rezza G. Coinfection of hepatitis C virus with human immunodeficiency
virus and progression to AIDS. Italian Seroconversion Study.
J Infect Dis 1995; 172:1503–1508.
15. Ockenga J, Tilmann HL, Trautwein C, Stoll M, Manns PM,
Schimitd ER. Hepatitis B and C in HIV-infected patients. prevalence and prognostic value. J Hepatol 1997; 27:18–24.
16. Greub G, Ledergerber B, Battegay M, Grob P, Perrin L, Firrer H,
et al. Clinical progression, survival, and immune recovery
during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study. Lancet
2000; 356:1800–1805.
17. Klein MB, Lalonde RG, Suissa S. The impact of hepatitis C virus
coinfection on HIV progression before and after highly active
antiretroviral therapy. J Acquir Immune Defic Syndr 2003;
33:365–372.
18. Sulkowski MS, Moore RD, Metha SH, Cheisson RE, Thomas DI.
Hepatitis C and progression of HIV disease. JAMA 2002;
288:199–206.
19. Sabin CA, Telfer P, Phillips NA, Bhagani S, Lee CA. The
association between hepatitis C virus genotype and human
immunodeficiency virus disease progression in a cohort of
hemophilic men. J Infect Dis 1997; 175:164–168.
20. Quirishi N, Kreuzberg C, Lüchters G, Effenberger V, Kupfer B,
Sauerbruch T, et al. Effect of antiretroviral therapy on liverrelated mortality in patients with HIV and hepatitis C coinfection. Lancet 2003; 362:1708–1713.
21. Pawlotsky JM. Treating hepatitis C in ‘‘difficult to treat’’
patients. N Engl J Med 2004; 315:422–423.
Optimistic perception of HIV/AIDS, unprotected sex
and implications for prevention among men who have
sex with men, São Paulo, Brazil
Cristiane G.M. da Silvaa, Dreyf de A. Gonçalvesb, Júlio C.B. Paccac,
Edgar Merchan-Hamannd and Norman Hearste
Background: This study examines the association between optimistic perceptions
about AIDS and unprotected sex among men who have sex with men (MSM) in the
city of São Paulo, Brazil.
Methods: A cross-sectional study was carried out among MSM in leisure areas of São
Paulo in 2003. We interviewed 161 participants aged 18–30 years.
Results: Thirty-nine per cent (95% confidence interval 32–47%) reported unprotected
anal sex with steady or casual partners in the previous 6 months. The optimistic
perception score created for this study was associated with unprotected sex
(P ¼ 0.01) and higher education (P ¼ 0.02). The quartile with the most optimistic
perception was 1.8 times more likely to engage in unprotected anal sex compared
with the quartile with the least optimistic perception.
Conclusion: This study suggests that the current situation regarding AIDS, which is
seemingly favourable, may create optimistic perceptions leading to unprotected sexual
practices. Prevention programmes, particularly for MSM, need to take this into
account.
AIDS 2005, 19 (suppl 4):S31–S36
Keywords: AIDS, antiretroviral agents, Brazil, gay men, HIV, men who have
sex with men, men’s health, prevention, sexual behaviour, unprotected sex,
young people
Introduction
The AIDS epidemic in Brazil has had from its outset a
disproportionate impact on the community of men who
have sex with men (MSM). In 2002, among male AIDS
cases over 13 years of age officially reported in Brazil, 16.6
and 10.3% were classified as belonging to the homosexual
and bisexual transmission categories, respectively [1].
Despite the advances achieved by non-governmental
organizations and government programmes, both of
which contributed to slowing the epidemic in MSM, this
population continues to be a priority for prevention
programmes. In São Paulo, the homosexual and bisexual
transmission categories make up an even higher proportion of reported adult male AIDS cases than nationally:
21.1 and 9.6%, respectively, in 2002 [2]. This study
was carried out in the city of São Paulo, an enormous
cosmopolitan metropolitan area of immense social and
cultural diversity that has the highest number of AIDS
cases of any Brazilian city [1].
The Brazilian HIV/AIDS epidemic must be considered
in the context of the advances and changes that have taken
place in the more than 20-year-old fight against HIV/
AIDS in Brazil. The Brazilian public healthcare service
has, since 1996, provided universal free access to
antiretroviral and other drugs for AIDS patients. This,
along with other improvements to the care given to
individuals living with HIV/AIDS, has substantially
reduced morbidity and opportunistic infections and
From the aNEPAIDS and the Brazilian National STD/AIDS Program – Ministry of Health, Brası́lia, the bNEPAIDS and São Paulo
State STD/AIDS, São Paulo, the cPathfinder International/Mozambique, Avenue Zimbabwe, 830 – Maputo City – Mozambique,
and the dUniversity of Brası́lia, Brası́lia, Brazil and the eUniversity of California, San Francisco, California, USA.
Correspondence to Cristiane Gonçalves Meireles da Silva, SHCGN 716 Bloco D apto. 109, CEP 70770-734, Brası́lia/DF, Brasil.
Tel: +55 61 344 88082; e-mail: [email protected]
S31
S32
greatly increased the survival time for individuals living
with AIDS [3,4].
Relatively few studies have examined unprotected sex in
the current improved AIDS context [5], particularly the
effects that the availability of antiretroviral therapy (ART)
may have on behaviour [6–8]. No studies in Brazil have
directly examined the association between an optimistic
perception regarding HIV/AIDS and risky behaviour,
but studies elsewhere suggest that unprotected sexual
practices may be related to not having experienced the
high mortality seen in the first decade of the epidemic,
and, more specifically, to an optimistic perception of the
beneficial effects of ART [9–15]. We conducted this
study to examine whether such an association exists
among young MSM in Brazil, a vulnerable population
for HIV/AIDS, with the goal of informing ongoing
prevention efforts.
Methods
A cross-sectional study was carried out among 161 MSM
from June to August 2003 in leisure areas in the central
region of the city of São Paulo. Recruitment was carried
out during selected weekend nights in establishments
such as bars and nightclubs catering for MSM. During
part of this period (in June), Gay, Lesbian, Bisexual and
Transgender Pride Day-related events were taking place
in the city, but no participants were contacted or
interviewed during large public events. MSM aged
18–30 years and living in the city of São Paulo or in the
metropolitan area were anonymously interviewed.
The questionnaire was partly based on other instruments
developed for previous studies in MSM. The questions
regarding the main focus, perceptions about AIDS, ART,
and AIDS risk, were developed on the basis of a
qualitative study carried out before this one [16]. The
questionnaire was pilot-tested on 30 MSM to evaluate the
language used and to verify the relevance of the questions.
Non-governmental organizations working in the geographical area were contacted before study implementation to avoid conflicts with their work.
The fieldwork team underwent training stressing specific
features of the target population, the logical structure of
the questionnaire, and simulated interviews. The team
also received AIDS prevention training, involving brief
counselling on safe sex practices calling attention to the
risk situations reported in the interview, referral to
sexually transmitted infection/HIV/AIDS diagnosis and
care services, and to condom and gel delivery services, to
be used for counselling after the interviews. The team
included college-educated health professionals and gay
movement activists, all of whom had experience in
research or educational activities.
Although the study team anticipated a high refusal rate
because of the sensitivity of questions vis-à-vis the interview in semi-public settings, there was only one refusal,
and only one participant terminated the interview before
completion. This may have been because of the fieldwork
team’s training and carefully choosing the methods
adopted. For instance, participants were not required
to express their answers orally during the intervieweradministered questionnaire, often being able silently to
choose among response categories by pointing.
We created a perception scale to measure participants’
degree of optimism regarding AIDS. Three five-point
agree–disagree items were included in the scale: ‘AIDS is
a deadly disease’ and ‘AIDS is a very serious disease’
(agreement scored as implying less optimism) and ‘People
living with HIV/AIDS lead a normal life’ (scored as
implying more optimism). These three questions were
each scored as 2 to þ2 and summed to give a scale. The
scale had possible values ranging from 6 to þ6 and a
Cronbach’s a coefficient of 0.57. This scale was the main
predictor variable. Other predictor variables were age,
self-reported colour/race, place of residence, schooling,
and income. The outcome variable for analysis was selfreported unprotected anal sex in the previous 6 months.
For score analysis, the median was used as the measure of
central tendency, and as dispersion estimates, the range of
quartile values. The median scores were compared using
the non-parametric Kruskal–Wallis test. Pearson’s chisquared and chi-squared test for trend were used to assess
the association between the outcome and the predictor
variables. The protocol was approved by the institutional
review boards of the STD/AIDS Reference and Training
Center of the São Paulo State Health Department and the
University of California at San Francisco. Ethical aspects
of this study included promoting prevention through the
fieldwork team and preserving the participants’ privacy,
despite the interviews being carried out in semi-public
places.
Results
The median age of the sample (n ¼ 161) was 23 years
(interquartile range 21–26), mean 23.5 (SD 3.4). Table 1
[17] shows the distribution of social and demographic
variables. Just over 50% identified themselves as white.
Subjects resided in all areas of São Paulo but mostly the
central and southern districts. Approximately 60% said
they had attended high school and had a monthly income
of three minimum wages (approximately US$ 270) or less.
Sixty-three participants (39.1%; 95% confidence interval
31.5–47.1%) reported unprotected anal sex in the previous 6 months with any partner. Unprotected anal sex
was reported more with steady partners (26.7%) than with
casual partners (17.4%).
Prevention of HIV/AIDS for MSM da Silva et al.
higher score in the optimistic perception scale was
associated with higher education (P ¼ 0.02) and unprotected anal sex (P ¼ 0.01). The proportion of the
participants in the quartile with the greatest optimism
who reported practising unprotected anal sex (51.4%) was
1.8 times greater than those in the lowest quartile (28%).
Table 1. Social, demographic, and behavioural characteristics of
men who have sex with men in São Paulo, Brazil, 2003.
Variables
Age (years)
18–24
25–30
Race
White
Black
Mixed (parda)
Place of residence
Southern MSP
Northern MSP
Eastern MSP
Western MSP
Downtown MSP
Metropolitan São Paulo
Schooling
Primary school
High school
University
Income (SM)a
Up to 3 SM
4 SM and more
Unprotected sex
No
Only oral sex
Anal sex with steady partner only
Anal sex with casual partner
Unprotected anal sex with casual partner
Yes
No
Unprotected anal sex with steady partner
Yes
No
N
%
99
62
61.5
38.5
77
26
48
60.0
17.2
31.8
36
27
29
12
40
17
22.4
16.8
18.0
7.5
24.8
10.6
23
96
42
14.3
59.6
26.1
78
52
60.0
40.0
41
44
34
27
28.0
32.9
21.7
17.4
27
119
17.4
82.6
42
104
26.7
73.3
Discussion
This study was carried out in a convenience sample of
young MSM who predominantly live in the central and
southern districts of the city of São Paulo, most of whom
reported being white and having the same sort of income.
Approximately 40% reported practising unprotected anal
sex, more frequently with steady partners. Responses to
the questions in our optimism scale indicate that the
majority of respondents believe that individuals with
HIV/AIDS can lead normal lives, and that a substantial
minority do not consider AIDS a very serious or deadly
disease. A higher optimism score is associated with higher
education and practising unprotected sex.
The association of HIV/AIDS optimism scores with
sexual practices suggests that what individuals believe
about the severity of HIV/AIDS may influence the
behavioural risks they take. These results add to those of
other studies [18], which point to the need for further
investigation of this phenomenon. We cannot say with
certainty whether this same association would hold in
other groups of MSM or in heterosexual populations.
However, it will be important to measure whether
increasing optimism about AIDS results in riskier behaviour as antiretroviral drugs become increasingly
available in more countries.
MSP, Municipality of São Paulo.
a
SM, Brazilian minimum monthly wage; 1 SM ¼ R$240.00 (approximately US$90.00). The median per capita income in São Paulo is
between two and three minimum salaries [17]. Sexual behaviour is in
the previous 6 months.
The optimistic perception of HIV/AIDS scores were as
follows: minimum 6, maximum þ6; 1st, 2nd and 3rd
quartiles: 5, 3 and 2, respectively. As shown in
Table 2, approximately 60% fully or partly agreed with the
first statement expressing an optimistic perspective. On
the other hand, the two remaining statements, with
which 22 and 7% fully or partly disagreed, reflected a less
optimistic perception of HIV/AIDS. Table 3 shows that a
Doing so will not be simple. Recent studies show no
uniform methodology for measuring ‘AIDS optimism’.
Our scale based on three questions is probably a crude
measure of a complex construct, although the observed
association with behaviour implies that it has some
validity. International studies have shown indications of
optimism among specific groups [9,19] and an association
Table 2. Distribution of responses to HIV/AIDS optimistic perception questions (%) among men who have sex with men in São Paulo, Brazil,
2003 (N U 161).
Agreement
Statement
Agreeing with this statement indicated
optimistic perception
People living with HIV/AIDS
lead a normal life
Disagreeing with these statements
indicated optimistic perception
AIDS is a deadly disease
AIDS is a very serious disease
Disagreement
Full
Partial
Don’t know
Partial
Full
24.2
34.2
1.2
16.2
24.2
61.5
85.7
16.8
7.5
–
–
14.3
4.4
7.5
2.5
S33
S34
Table 3. Distribution of men who have sex with men by social and demographic variables, HIV/AIDS optimistic perception score, and sexual
practices in the previous 6 months, São Paulo, Brazil, 2003.
Unprotected
anal sex
Optimistic perception score
Variables
Age (years)
18–24
25–30
Race
White
Black
Mixed (parda)
Place of residence
Southern MSP
Northern MSP
Eastern MSP
Western MSP
Downtown MSP
Metropolitan São Paulo
Schooling
Primary school
High school
Income (1 SM ¼ R$240.00
¼ US$80.00)
Up to 3 SM per month
4 SM and more per month
Optimistic perception score
(6)–(5) (1st quartile)
(4)–(3) (2nd quartile)
(2) (3rd quartile)
(1)–(þ6) (4th quartile)
N
%
Median
99
62
61.5
38.5
3
3
Interquartile
range
P valuea
No
unprotected
anal sex
N
%
N
%
40
23
40.4
37.1
59
39
59.6
62.9
28
13
17
36.4
50.0
35.4
49
13
31
63.6
50.0
64.6
10
11
14
3
15
10
27.8
40.7
48.3
25.0
37.5
58.8
26
16
15
9
25
7
72.2
59.3
51.7
75.0
62.5
41.2
8
30
34.8
40.6
15
57
65.2
59.4
30
22
38.5
42.3
48
30
61.5
57.7
14
13
17
19
28.0
34.2
47.2
51.4
36
25
19
18
72.0
65.8
52.8
48.7
0.68b
0.96
5, 2
5, 1
0.84
77
26
48
60.0
17.2
31.8
3
2
3
5, 2
5, 2
5, 0.5
0.32
36
27
29
12
40
17
22.4
16.8
18.0
7.5
24.8
10.6
3
3
3
3
3
2
5.5, 2
5, 2
5, 1
4.5, 2
5, 2
4, 0
23
96
14.3
59.6
5
3
6, 2
5, 1
0.02
0.44
78
52
60.0
40.0
3
2
–
–
–
–
–
–
–
–
–
–
–
–
5, 2
4, 2
–
–
–
–
–
–
–
–
P value
0.41b
0.23b
0.86b
0.66b
0.01c
MSP, Municipality of São Paulo.
a
Kruskal–Wallis test.
b
Pearson’s chi-squared.
c
Chi-squared for trend.
between unprotected sex and optimistic perceptions of
the effects of ART [8]. This is the first such study to be
published from Brazil. Studies elsewhere have tended to
focus more on knowledge and perception regarding
specific difficulties and side-effects associated with ART
rather than general optimism regarding the severity of
AIDS. We also asked such specific questions about ART
in our interview, but did not find the responses to be
particularly informative or associated with behaviour; we
therefore do not present these data in this article.
The greater prevalence of unprotected sex with steady
partners that we observed has also been found in other
studies involving MSM in Brazil [20,21]. This presents
important challenges to education and health promotion
related to the subjective aspects of trust existing between
sexual partners, both in the gay and heterosexual scenarios
[22]. The dynamics of the gay scene resulting from
cultural aspects of each city and context [23] may require
more creative, alternative prevention strategies promoting
less rigid behavioural norms. These new directives
go beyond the motto ‘always use a condom’ in the
negotiation process between partners. Further research
needs to focus on the kinds of partnerships people
establish and how they perceive them. It is also necessary
to focus on the role of multiple partnerships and their
association with a higher incidence of sexually transmitted infections [24–26].
As a result of our recruiting strategy, the subjects in this
study are not necessarily representative of MSM in Brazil
in general. However, the study characterizes the profile of
one subgroup: individuals attending leisure areas and
cruising places looking for sex partners. These venues will
continue to demand priority for preventative actions
because of the diversity and high number of patrons.
Other studies conducted in settings where MSM
congregate show that such places represent an appropriate
opportunity for implementing preventative actions [27].
The changes resulting from ART availability and from
the effects of HIV/AIDS control policies should be
Prevention of HIV/AIDS for MSM da Silva et al.
understood and taken into account when updating
prevention strategies, particularly those directed towards
young gay men. They should aim at avoiding any
perception that AIDS is now a ‘normal’ and non-fatal
disease. Such a strategy may help to prevent individual and
collective relapses to unsafe sexual practices [13],
especially if employed in a manner that pays special
attention to cultural diversity [28].
The participants in this study are of a generation that did
not experience the degree of suffering and prejudice
faced in the first decade of the epidemic. Their generation
had greater access to information on HIV/AIDS and the
means of protection. In addition, to understand the results
better, one should also look for explanations in a globalizing gay culture. In this context, the diffusion of
cultural meanings, such as those related to ‘barebacking’,
may influence the expansion of this practice among
young gay men in big cities [29]. There is a need to
investigate what has been called ‘conscious exposure’,
which is currently a central topic in issues of prevention
among MSM [7,8,21,30].
Progress in the treatment of HIV/AIDS in Brazil provides
real grounds for increased optimism. Nevertheless, this
study suggests that excessive optimism may create new
challenges for prevention among some young gay
men. More studies are needed in Brazil and in other
Latin American countries [31] to obtain a better
understanding of this changing context and its implications [30,32]. Prevention programmes should stress that
HIV is still a serious risk and that treatment is still far from
a cure.
Acknowledgements
The authors feel deeply in debt to the research staff.
They also thank the São Paulo Gay, Lesbian, Bisexual
and Transgender Pride Parade Association for their
help.
Sponsorship: This study was funded by the Center for
AIDS Prevention Studies of the University of California,
San Francisco, the STD/AIDS Program of São Paulo
State, and the Brazilian Ministry of Health STD/AIDS
Program.
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Bulletin of the City of São Paulo, November 2004. Available
at: http://www10.prefeitura.sp.gov.br/dstaids/pdf/boletim2004.
pdf. Accessed: March 2, 2005.
3. Galvão J. Access to antiretroviral drugs in Brazil. Lancet 2002;
360:1862–1865.
4. Marins JRP, Jamal LF, Chen SY, Barros MB, Hudes ES, Barbosa
5. Boily MC, Bastos FI, Desai K, Masse B. Changes in the transmission dynamics of the HIV epidemic after the wide-scale use of
antiretroviral therapy could explain increases in sexually transmitted infections: results from mathematical models. Sex
Transm Dis 2004; 31:100–113.
6. Laporte A. A new decline in preventive behaviours among
homosexual men: the role of highly active antiretroviral therapy? Euro Surveill 2002; 7:15–16.
7. Kippax S, Race K. Sustaining safe practice: twenty years on. Soc
Sci Med 2003; 57:1–12.
8. Lert F. Advances in HIV treatment and prevention: should
treatment optimism lead to prevention pessimism? AIDS Care
2000; 12:745–755.
9. International Collaboration on HIV Optimism. HIV treatments
optimism among gay men: an international perspective.
J Acquir Immune Defic Syndr 2003; 32:545–550.
10. Van de Ven P, Rawstorne P, Nakamura T, Crawford J, Kippax S.
HIV treatments optimism is associated with unprotected anal
intercourse with regular and with casual partners among
Australian gay and homosexually active men. Int J STD AIDS
2002; 13:181–183.
11. Elford J, Bolding G, Sheerr L. High-risk sexual behavior
increases among London gay men between 1998 and 2001:
what is the role of HIV optimism? AIDS 2002; 16:1537–
1544.
12. Knox S, Van de Ven P, Prestage G, Crawford J, Grulich A, Kippax
S. Increasing realism among gay men in Sydney about HIV
treatments: changes in attitude over time. Int J STD AIDS 2001;
12:310–314.
13. Perez K, Rodes A, Casabona J. Monitoring, HIV prevalence and
behaviour of men who have sex with men in Barcelona, Spain.
Euro Surveill 2002; 7:19–22.
14. Stall RD, Hays RB, Waldo CR, Ekstrand M, McFarland W. The
gay ’90s: a review of research in the 1990s on sexual behavior
and HIV risk among men who have sex with men. AIDS 2000;
14 (Suppl. 3):S101–S114.
15. Stall R, Pollack L, Mills TC, Martin JN, Osmod D, Paul J, et al.
Use of antiretroviral therapies among HIV-infected men who
have sex with men: a household-based sample of 4 major
American cities. Am J Public Health 2001; 91:959–964.
16. Silva CGM, Gonçalves DA, Pacca JCB, Hearst N. Perceptions
regarding antiretroviral treatment and sexual behavior among
young MSM in São Paulo, Brazil. In: XVth International AIDS
Conference. Bangkok: 2004. Abstract n8 WEPECG108
17. State of São Paulo, Foundation for Data Analysis – State Secretariat of Economics and Planning. Classification of family and
per capita Income. Available at: http://www.seade.gov.br/cgibin/pcvv98/tabela?pcv1998sp/t0604.html. Accessed: March 2,
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18. Ostrow DE, Fox KJ, Chmiel JS, Silvestre A, Visscher BR,
Vanable PA, et al. Attitudes towards highly active antiretroviral
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775–780.
19. Auld MC. Choices, beliefs, and infectious disease dynamics.
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20. Brazilian STD-AIDS Control Program – Ministry of Health. Bela
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05). Brası́lia: Ministry of Health; 2001.
21. Souza CT, Bastos FI, Lowndes CM, Szwarcwald CL, Santos EM,
Castilho EA, et al. Perception of vulnerability to HIV infection
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Brazil. AIDS Care 1999; 11:567–579.
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25. Rietmeijer CA, Patnaik JL, Judson FN, Douglas JM Jr. Increases
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Prevention of mother-to-child transmission of HIV in
São Paulo State, Brazil: an update
Luiza Harunari Matidaa, Mariliza Henrique da Silvaa, Ângela Tayraa,
Regina Celia de Menezes Succib, Maria Clara Giannaa, Alexandre
Gonçalvesa, Heráclito Barbosa de Carvalhoc and Norman Hearstd
Background: São Paulo State has had the largest number of paediatric AIDS cases in
Brazil. Since 1996, São Paulo (and Brazil nationally) has implemented an aggressive
programme to reduce perinatal transmission. We have gathered available indicators to
examine the programme’s impact.
Methods: We obtained data on reported AIDS cases from the AIDS surveillance system;
data on the number of mother/infant pairs treated with zidovudine from the state
logistics office responsible for distributing HIV medication; and the rates of perinatal
transmission from a multicity study of the Brazilian Pediatric Society that includes a
number of São Paulo facilities, which were compared with an independent study in
1995. The years for which data were available varied according to the source of the
indicator.
Results: Annual reported cases of AIDS as a result of perinatal transmission fell 58.9%
from 1997 to 2002. The number of cases treated with zidovudine increased 73.7% from
1997 to 2004. The rate of perinatal transmission among babies born to HIV-positive
mothers fell from 16% in 1995 to 2.4% in 2002 in the reference clinics that participated
in the Brazilian Pediatric Society study.
Conclusion: Both process and outcome indicators point to the effectiveness of efforts to
reduce perinatal transmission in São Paulo State. ß 2005 Lippincott Williams & Wilkins
AIDS 2005, 19 (suppl 4):S37–S41
Keywords: AIDS, Brazil, HIV, mother-to-child transmission, perinatal
transmission, prevention
Introduction
In 2004, according to the World Health Organization,
approximately 640 000 children under the age of 15 years
were infected with HIV worldwide [1]. Mother-to-child
transmission (MTCT) of HIV, which can occur during
intrauterine life, during delivery, or through breastfeeding, accounts for approximately 90% of all HIV infections
among these children [2]. Approximately 2 million HIVpositive pregnant women were in need of prevention
measures against MTCT of HIV in 2003, but only 9% of
these women received such interventions. In sub-Saharan
Africa, this rate was much less [2].
In the absence of preventative interventions, namely
antiretroviral treatment during pregnancy and delivery
and for the newborn and avoiding breastfeeding, up to
32.5% of children born to HIV-positive mothers become
infected [3]. Of these, 15–20% occur during pregnancy,
over 50% occur during labour and delivery, and up to 29%
occur during breastfeeding [4,5]. In the period before the
availability of preventative interventions, the rates of
MTCT of HIV varied greatly: 11–14% in western
Europe, 20–28% in the United States, and 30–35% in
certain African countries [2]. Data available in Brazil
indicate rates between 13 and 20%, depending on
breastfeeding practices [6].
From the aSão Paulo State STD/AIDS Program, the bFederal University of São Paulo (UNIFESP), the cUniversity of São Paulo (USP),
São Paulo, Brazil and the dUniversity of California, San Francisco, California, USA.
Correspondence to Luiza Harunari Matida, Av. Padre Pereira de Andrade, 127, ap.71, São Paulo, Brazil CEP: 05469-000.
Tel: +55 11 30223136; fax: +55 11 30224439; e-mail: [email protected]
S37
S38
Throughout the evolution of the epidemic, a number of
advances have been incorporated into the care of HIVpositive individuals, especially HIV-infected pregnant
women. Advances in the prophylaxis, treatment, and care
provided to these women has changed the rates of
MTCT. In 1994, the Pediatric Aids Clinical Trials Group
(PACTG 076) [3] demonstrated the preventative efficacy
of administering zidovudine to the mother in the prenatal
period and during delivery, and administering it to the
newborn for 6 weeks after delivery. The rate of MTCTof
HIV in settings that offered high-quality diagnostic and
clinical care along with access to medications from the
beginning of prenatal care has subsequently been reduced
to levels close to 2% [7–9]. Such interventions are widely
available in developed countries. Brazil was one of the
first developing countries to implement antiretroviral
therapy for HIV in general and for the prevention of
MTCTof HIV [10] (Table 1) [11,12]. In Brazil, access to
prophylactic treatment with zidovudine at the time of
delivery for HIV-positive women was estimated to be
49% in 2003 [13].
São Paulo State, with a population of 39 876 000, has the
largest percentage of reported AIDS cases in Brazil (i.e.
42.3%) and the highest number of MTCT cases
nationwide (40.3%) [14,15]. São Paulo State was the
first Brazilian state to implement specialized services for
the care of HIV/AIDS patients, as early as 1983 [10].
Intervention strategies for the reduction of MTCT of
HIV that have been introduced and implemented in São
Paulo State, following the recommendations of the
Brazilian STD/AIDS programme, include: specialized
care (services that work with multiprofessional teams to
assist individuals living with HIV/AIDS); training of
healthcare professionals to follow official prophylactic/
therapeutic guidelines; access to antiretroviral drugs;
Table 1. Timeline of significant events and the initiation of strategies
aimed at reducing mother-to-child transmission of HIV in São Paulo
State, Brazil.
1983
1987
1990
1994
1995
1996
1997
2000
2001
2002
First notified case of HIV in a woman
Beginning of the São Paulo State STD/AIDS Program
First reported case of AIDS by MTCT in a child
Prophylaxis against opportunistic infections
Monotherapy (adults and children)
Specialized outpatient facilities
Implementation of Protocol ACTG076
Brazilian Prophylactic-Therapeutic Guidelines
PCR-RNA testing
Recommendation against breastfeeding
Counselling and voluntary HIV testing for all pregnant
women
Double therapy (adults and children)
Protease inhibitors
Triple therapy (adults and children)
Reporting HIV in pregnant women and exposed children
Voluntary rapid testing for HIV in maternity units
Genotyping
Infant formula distribution
MTCT, Mother-to-child transmission; PCR, polymerase chain reaction; STD, sexually transmitted disease. Source: PBDST/AIDS [11];
CEDST/AIDS-SP [12].
laboratory diagnosis (HIV testing, CD4 cell count, viral
load, genotype and opportunistic infections assays);
recommendations against breastfeeding; offering HIV
tests for all pregnant women; compulsory reporting of all
HIV-positive pregnant women and of children exposed to
HIV; rapid HIV tests in maternity units; and providing
infant formula to all children with HIV-positive mothers
[11]. These initiatives took place in the context of steadily
increasing resources available for the diagnosis and treatment of HIV/AIDS (Table 1), including universal free
access to triple antiretroviral therapy starting in 1996 [16].
These efforts represent a substantial commitment of
resources for a middle-income country such as Brazil.
Therefore, it is essential to measure their impact. Previous
studies have reported reductions in MTCT in Brazil
[12,17,18,19], but these have all been based on the
experience of a single city or model clinical service. No
published studies have examined results on a populationwide basis for broad geographical areas. This paper
examines the available data for selected process and
outcome indicators to provide an update on the current
status of efforts to reduce MTCT of HIV in São Paulo
State, the most populous state in Brazil and the epicentre
of the Brazilian AIDS epidemic.
Methods
The present study was based on data from São Paulo State
Epidemiological Surveillance, which, through the National System for Disease Control, Sistema Nacional de
Agravos de Notificação (SINAN), receives and analyses
reported cases of AIDS and of HIV in pregnant women
and in exposed children. We included cases with a date of
diagnosis to December 2002, and entered into the system
by June 2004, so as to minimize reporting and entry delay
bias [20].
Data on intravenous zidovudine and on the use of rapid
tests for HIV detection were provided by the São Paulo
State STD/AIDS Program, which controls the purchase
and distribution of these products. We compared this with
the total number of deliveries per year [21], and estimated
HIV seroprevalence among women giving birth from the
National Sentinel Study of HIV and the UNAIDS
seroprevalence survey [22,23].
To evaluate the rate of MTCT of HIV in São Paulo State
throughout the years, we made use of the results of two
previous studies. The first study was conducted in 1995,
in centres of excellence for the treatment of children
exposed to and infected by HIV in four São Paulo State
municipalities with populations of over 700 000 [6]. That
study was a retrospective evaluation of 434 children,
considering clinical, laboratory, and prophylactic aspects
of mothers and children. The Brazilian Pediatric Society
coordinated the second study [24]. This national
collaborative study involves centres throughout the
Mother-to-child transmission of HIV in Brazil Matida et al.
country participating in a common effort to measure rates
of MTCT of HIV. It includes 31 specialized facilities in
São Paulo State, out of a total of 68 participating facilities
countrywide. The São Paulo State component of the
study comprises 1944 (48.6%) of 4004 reported cases of
children exposed to HIV in Brazil born between 2000
and 2002. The mothers were diagnosed with HIV infection during pregnancy, delivery, or up to 3 months after
birth. Babies were considered HIV positive if they tested
positive for viral RNA at least twice after birth or if they
tested positive for HIV antibodies at 15 months of age.
Results
The number of zidovudine treatments dispensed for
intrapartum use in São Paulo State increased rapidly from
784 in 1997 to 2861 in 2001 and then stabilized at
approximately this same level, with 2982 treatments
dispensed in 2004 (São Paulo State STD/AIDS Program).
The denominator of HIV-infected women giving birth is
more difficult to estimate. Total recorded births in São
Paulo State were 623 176 in 2002 [21]. No studies to date
have systematically measured the prevalence of HIV
infection in pregnant women in São Paulo State; sentinel
surveillance in specific sites together with smaller
seroprevalence studies [22,23] suggest an approximate
prevalence of 0.5–0.6%. If correct, this would suggest
between 3116 and 3739 births to HIV-positive women
per year and coverage with intravenous zidovudine of
between 67 and 81%.
As 85% of women receive prenatal care in São Paulo State,
and are thus likely to undergo HIV testing, there remains
a maximum of approximately 15% of women in need of
rapid HIV testing in maternity units [11]; in 2003, 70 600
rapid tests were utilized in 609 317 deliveries. This rate of
11.6% thus appears to approach the potential need.
Figure 1, which shows reported cases of AIDS as a result
of MTCT from 1987 to 2002 by year of diagnosis, shows a
decline from 389 cases reported in 1997 to 160 cases in
2002, a 58.9% decrease. The figure also shows an 87.8%
decrease in deaths from AIDS caused by MTCT from 164
in 1994 to 20 in 2002. Not surprisingly, as São Paulo State
accounts for approximately half of all cases of AIDS,
national surveillance data (not presented here) show
similar trends [14].
Figure 2 presents data from studies conducted to measure
rates of MTCT of HIV in São Paulo State, showing an
infection rate of 16% in 1995 [10], and of a second study
analysing data from children born to HIV-positive
mothers in the 2000–2002 period, when access to more
antiretroviral drugs was available (Table 1) [24]. This
shows rates of MTCT falling to 9.0% in 2000 (95%
confidence interval, 7.0–11.3%), 7.5% in 2001 (5.6–
9.9%), and 2.4% in 2002 (1.3–4.1%).
450
400
350
300
250
200
150
100
50
0
87
89
91
93
95
97
99
2001
Fig. 1. Reported AIDS cases resulting from mother-to-child
transmission in São Paulo State: cases and deaths, by year of
diagnosis, among children under 13 years of age, 1987–
2002. & Cases; –— deaths. Source: São Paulo State STD/AIDS
Program.
Discussion
The process and outcome data presented suggest
substantial progress in reducing MTCT of HIV in São
Paulo State. UNAIDS has a goal of reducing cases of
AIDS by MTCT internationally of 25% by 2005 and of
50% by 2010 [25]; in São Paulo State, cases of AIDS
caused by MTCT fell by 58.9% between 1997 and 2002
[26]. This reduction in AIDS cases was probably a result of
a combination of reduced MTCT and the delayed
progression of HIV infection to AIDS among infected
children because of improved treatment.
In the United States and other developed countries, reductions in the number of MTCT-related cases have been
observed since 1995 as a result of the wide coverage of
HIV testing before or during pregnancy and the prompt
incorporation of antiretroviral drugs in prophylaxis and
in the treatment of infected pregnant women [7–9].
Similar success, however, is not being achieved by most
developing countries, which to varying degrees face
difficulties in implementing interventions for the prevention of MTCT as a result of logistic deficiencies and
budget restrictions [27]. Nevertheless, a comparison of
the rates of infection by MTCT of HIV in New York
State and in São Paulo State shows similar decreasing
18
16
14
12
10
8
6
4
2
0
16
9
7.5
2.4
1995
2000
2001
2002
Fig. 2. HIV infection rates (%) in babies born to HIV-positive
mothers in São Paulo State, 1995–2002. Source: Tess et al.
[6] and UNAIDS/UNICEF/WHO [23], with permission.
S39
S40
trends: between 1997 and 2002, the rate of MTCT in
New York State fell from 10.9 to 2.4% [28], whereas in
São Paulo State in 1995–2002 the rate fell from 16 to
2.4% [24], at least in the centres participating in the
Brazilian Pediatric Society study. Although there are
many differences between the situation in New York and
in São Paulo, these data indicate that a developing country
can obtain results similar to those of a rich country when
similar interventions are implemented.
The evaluation of the indicators presented in this paper is
limited by the quality and accuracy of the available data.
For example, AIDS case reporting in Brazil, although
good by developing country standards, is far from
complete. Results from São Paulo State do not necessarily
apply to other Brazilian regions. The country’s size and
cultural differences and the deficient infrastructure of a
number of healthcare services pose a great challenge for
the prevention of MTCT of HIV throughout Brazil as a
whole.
We conclude that, despite difficulties in the identification
of the relative contribution of each of the factors
presented, there has been an important reduction in the
rate of MTCT of HIV in São Paulo State, comparable to
that observed in developed countries. At the same time,
many challenges remain. To reduce MTCT still further, it
will be necessary to identify all HIV-positive pregnant
women and to make certain that treatment guidelines are
consistently applied. These guidelines include the
replacement of breast milk by formula feeding or
pasteurized human milk [11], and increasingly recommend treating the mother (and thereby preventing
MTCT) with combination antiretroviral therapy. Consistent implementation of these strategies will require
continued training, quality improvement, and the
monitoring of all MTCT prevention strategies, as well
as multifaceted efforts to make sure that all women receive
early prenatal care. Ultimately, the goal should be to
come as close as possible to the elimination of MTCT of
HIV.
Acknowledgements
The authors would like to thank the National STD/AIDS
Program for their financial support, the São Paulo State
STD/AIDS Program for technical support, the Public
Health Faculty/São Paulo University for administrative
support; and Dr Francisco Inácio Bastos for helpful
comments.
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December 2003. Available at: http://www.crt.saude.sp.gov.br.
Accessed: November 4, 2004.
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syphilis. Available at: http://www.aids.gov.br/final/novidades/
reuniao_coordenadores/Reunião%20de%20Coordenadores_
Transmissão%20vertica_versão%2014set2004.ppt Accessed:
November 4, 2004.
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MM, et al. Vertical transmission of HIV in Rio de Janeiro,
Brazil. AIDS 2003; 17:1853–1855.
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M, et al. Successful prevention of HIV transmission from
mother to infant in Brazil using a multidisciplinary team
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Fogaea ER, et al. Decrease in vertical transmission: a successful
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Brazil_EN.pdf. Accessed: November 9, 2004.
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[Abstract OR 840].
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10d_Glaros.ppt Accessed: November 18, 2004.
S41
Factors associated with condom use among youth
aged 15–24 years in Brazil in 2003
Gabriela Calazansa,d, Teo W. Araujoa,
Gustavo Venturib,d and Ivan França Juniorc,d
Objective: To analyse factors associated with the lack of condom use among young
people at last sexual intercourse with a steady or casual partner.
Design: A cross-sectional study involving 1170 household interviews and designed
to build a representative sample of the population of young Brazilian residents aged
15–24 years (2003).
Methods: In the multivariate analysis of data, non-conditional logistic regression
modelling was applied to assess the determinants of condom use at last sexual
intercourse among young people with steady or casual partners.
Results: The overall level of condom use at last sexual intercourse was high (60%),
although it was significantly more common in casual sexual partnership. Cohabitation
was associated with a lack of condom use in both casual and steady partner encounters.
In addition, being female, having less schooling, having no work history, and per capita
family income above the minimum wage were factors related to not using condoms in
the group of young people who had their last sexual encounter with steady partners.
Among young people with casual partners, such factors included a positive history of
alcohol use, first sex at 9–16 years of age, inadequate knowledge of AIDS treatability
and bereavement related to violence.
Conclusion: This study confirmed that the determinants of condom use among youth
during last sexual intercourse vary according to whether the partner was casual or
steady. Prevention campaigns should develop specific messages for each of these
contexts.
AIDS 2005, 19 (suppl 4):S42–S50
Keywords: condoms, Latin America, prevention of sexual transmission,
risk factors, sexual behaviour
Introduction
Literature on AIDS prevention research has indicated that
young people are an important target population because
of an increased risk of sexually transmitted disease (STD)/
HIV infection and the fact that behavioural patterns
established in youth may persist throughout life [1–3].
Historically in Brazil, young people present higher
percentages of condom use compared with all other age
groups [4–6].
Condom use varies significantly, among young people as
well as among adults, according to the type of sexual
relationship, defined as either ‘casual’ or ‘steady’ [4,5,7–
13]. When studying types of partnership, condom use has
been found to be significantly less frequent and less
consistent in steady than in casual relationships [11,13].
There have been few specific national studies involving
youth and focusing on condom use, such as those conducted in Ghana [14] and in Mexico [15]. Most studies are
From the aCentro de Referência e Treinamento DST/AIDS, the bCriterium Assessoria em Pesquisas, the cFaculdade de Saúde
Pública da Universidade de São Paulo and the dNúcleo de Estudos para a Prevenção da Aids da Universidade de São Paulo,
Nepaids/USP, São Paulo, Brazil.
Correspondence to Gabriela Calazans, Coordenação Estadual de DST/AIDS – SP, Rua Santa Cruz, 81, 04121-000 São Paulo, SP,
Brasil.
S42
Condom use among youth in Brazil Calazans et al.
restricted to high school students. Studies examining the
differences in patterns of condom use according to sexual
partners among young adults are rare [16]. In addition,
studies rarely examine factors associated with condom use.
In a recent review of successful HIV/AIDS control
programmes, it was noted that the strategy of promoting
condom use is effective in contexts in which transmission
occurs in commercial sex settings and in male–male
relationships, but not in contexts of a high prevalence of
heterosexual transmission [2]. One of the focuses of the
Brazilian HIV/AIDS programme has been the promotion
of condom use [4].
In this study, we aimed to evaluate condom use at last
sexual intercourse, and analyse factors associated with
condom use among young people according to whether
sexual partners were steady or casual.
Methods
In November–December of 2003, a national crosssectional study, involving youth aged 15–24 years, was
carried out in Brazil. The study, which included both
sexes and all social strata, was designed to build a representative sample of the population of young Brazilians. This
population, estimated at 34.1 million, represents 20% of
the total population [17].
The data used in this article for a condom use analysis were
originally collected in a broader study that investigated
relevant topics for creating a sociocultural profile of
Brazilian youth based on 3501 interviews [18]. The sample
was divided into three subsamples comprising a common
set of 57 questions and a set of specific questions. In the
present study, we analysed the data from subsample B,
which included information related to last sexual
intercourse and drug use, as well as values and attitudes
with regard to experiences with violence and sex relations.
The first stages of the sampling procedure for each of the
subsamples were probabilistic (proportional to the size
selection of cities, census tracts and household),
combined with sex and age quotas for the selection of
individuals (final stage). Given this procedure of quota
control, refusals were immediately replaced in the same
household by individuals of the same sex and age profile,
and were not counted. In subsample B, 1170 interviews,
carried out in 198 municipalities, were stratified by
geographical location (capital and countryside, urban and
rural) and by size (small, medium-sized and large),
encompassing 25 of the 27 Brazilian states. In nine
metropolitan regions and in the Federal District of
Brası́lia, the sample was expanded as follows: the
proportion of interviews in those areas was increased
from 29.73% (which corresponded to its original weight)
to 34.27%, in order to reach 1200 from the 3501
interviews. For the national results, those interviews were
multiplied by a correction factor (0.86) in order to reduce
them to its original proportionality.
The inclusion criterion for this condom use analysis was
being sexually active in the past 12 months. A total of 316
(27%) and 173 (15%) young people were excluded from
the sample, respectively, because they were not sexually
active or because they reported that their last sexual
encounter had occurred more than a year before the
interview. Therefore, the final sample consisted of 681
young people who had been sexually active within the
preceding year.
The household survey instrument was a 90-question
structured questionnaire. An informed consent form was
read to individuals before the interview and stated the
following: (i) complete anonymity of the interviewee was
guaranteed; (ii) the interviewee had the option of
declining to answer any question; (iii) questions were
designed to elicit opinions, and there were no right or
wrong answers. The interviewers were instructed to
interview the young people individually and in private.
An analysis of the correlates of a lack of condom use
among young people at last sexual intercourse was carried
out after subdividing the study population into two
groups: those whose last sexual encounter was with a
steady partner and those whose last sexual encounter was
with a casual partner. Participant-driven definitions of the
type of partner were used.
Variables
Sociodemographics
The young people were divided according to age groups:
15–17, 18–20 and 21–24 years. They were also
categorized according to their marital status: (i)
widow/er or divorced; (ii) single; or (iii) cohabiting
(whether married or not).
Skin colour-related data was self-reported based on the
options: black, mulatto, white, Asian and indigenous [19].
Data were grouped into two categories: black (black and
mulatto) and non-black (Asian, indigenous and white).
We created three employment categories: never worked
(and were not seeking a job); working; and seeking a job.
We also created four categories of religion: protestant or
evangelical; spiritism, Umbanda or Candomblé; catholic;
and other. The youths’ educational background was
grouped into four categories: 0–4; 5–8; 9–11; and 12 or
more years of schooling.
Sexual and reproductive life
Data collected concerning the last sexual intercourse
were: condom use and whether the partner was steady or
casual. In addition, they were asked about the age of first
sexual intercourse and their sexual orientation, as well as
S43
S44
about parenthood. In addition, the adequacy of their
knowledge about AIDS treatability (whether it is curable,
incurable but treatable, or fatal) was assessed.
Other life experiences
Participants were queried about their previous use of
alcohol, marijuana or cocaine. In order to evaluate sexrelated values, interviewees were also asked to express
agreement or disagreement with seven statements about
gender roles.
During the interview, the young people were asked if
they had ever experienced psychological violence
(perceived humiliation, disrespect or discrimination) or
abuse (from an immediate family member or relative). In
addition, they were asked whether they had experienced
bereavement associated with violence or the loss of
someone close to them (a relative or a friend) through
accident, homicide, suicide, etc., and whether they had
ever personally witnessed the body of someone who had
had a violent death.
people in the steady partner group were, on average,
slightly older (means 20.4 versus 19.1 years in the casual
group, a significant difference of 1.3 years). Moreover, the
steady partner group presented higher proportions of
women and of cohabiting individuals. There were no
significant differences in other social demographic
variables across the two groups studied. There were five
individuals that besides cohabiting had their last sexual
intercourse with a casual partner (Table 1).
We found that those in the steady partner group started
their sexual life much later, that is, 35% were over
17 years, compared with 17% among those in the casual
partner group. More individuals in the steady partner
group had children. With regard to their opinions on sex
role statements, casual partner group members were more
likely to believe that men should have the last word within
the couple, and were less likely to believe that politics
would improve if there were more women in important
positions. Alcohol use was more common among the
casual partner group (84%).
Analysis
Differences in proportions were assessed using the chisquared test, with a 5% level of significance. Nonconditional, weighted logistic regression modelling was
performed. When a given variable attained a value of
P < 0.15 in the univariate analysis, it was selected by a
forward stepwise selection procedure to identify significant predictors of condom use. Associated P values of
5% or less were considered statistically significant. The
database was originally compiled using the SPSS package
(SPSS Inc., Chicago, Illinois, USA), and data analysis
was carried out with Stata 8.0 (STATA Corp., College
Station, Texas, USA).
There were no significant differences between the two
groups in terms of sexual orientation, life experiences
regarding violence, marijuana or cocaine use and
knowledge on AIDS treatability.
Results
Bereavement associated with violence was associated with
less condom use at last sexual intercourse, as were
inadequate knowledge about AIDS treatment and having
the opinion that men must be more sexually experienced
than women. In contrast, no significant differences in
condom use were found with regard to life experiences
involving violence or alcohol, cocaine or marijuana use.
Profile of the young adults in this study
A significant percentage (60%) reported condom use at
last sexual intercourse, and there was a significant
difference in condom use according to the type of
partner: 80% used condoms with casual partners,
compared with 49% when partners were steady. These
sexually active young people were predominantly single
men, aged 21–24 years, black and catholic. Moreover,
they had 9–11 years of schooling, and were seeking a job.
Two-thirds of the young people had their last sexual
encounter with a steady partner (Table 1). Only 3%
reported homosexual orientation.
Differences in condom use at last sexual
intercourse according to type of partner
The two groups (those with steady or casual sex partners)
differed in terms of sex, age, marital status, condom and
alcohol use. There were more men (78%) and singles
(96%) in the casual partner group. In contrast, young
Correlates of lack of condom use during last
intercourse when the partner was ‘steady’
In univariate analysis (Table 2), cohabitation, not having
children, being a woman and never having worked were
associated with a lack of condom use.
Those youths in the sample with less schooling (0–4 or 5–8
years), as well as those in the older age group (21–24 years),
also reported lower condom use at last sexual intercourse.
In multivariate analysis, cohabitation, being a woman,
having less than 4 years of schooling and never having
worked were factors independently associated with a lack
of condom use at last sexual intercourse. Reporting a per
capita family income above the minimum wage also
emerged as an independent factor for the lack of condom
use, although this stratum did not show any association in
univariate analysis (Table 2).
Correlates of lack of condom use at last sexual
intercourse when the partner was ‘casual’
In both univariate and multivariate analyses (Table 3),
condom use was found to be lower among those who
Table 1. Sample of young people (aged 15–24 years) sexually active in the past year according to type of relationship at last sexual intercourse,
distributed by sociodemographic variables and condom use, Brazil, 2003.
Variable
Age (years)
15–17
18–20
21–24
Marital statusa
Single
Cohabiting (whether married or not)
Widowed/divorced
Sex
Male
Female
Skin colour
Black
Not black
Years of schooling
0–4
5–8
9–11
12 or more
Per capita income ( minimum wage)
0–0.5
0.5–1
1–2
2 or more
Unknown
Employment
Never worked
Working
Seeking a job
Religion
Protestant/evangelical
Spiritism/Umbanda/Candomblé
Catholic
Others
Condom useb
Yes
No
Alcohol use
Yes
No
Marijuana use
Yes
No
Cocaine use
Yes
No
Parenthood
Yes
No
Within the couple, men should have
the last word
Yes
No
Politics would improve if women were
in important positions
Yes
No
Sample n (%)
Steady n (%)
Casual n (%)
116 (17)
292 (33)
269 (50)
59 (13)
182 (32)
201 (55)
57 (24)
110 (36)
68 (40)
0.0003
484 (71)
179 (27)
12 (2)
259 (58)
174 (40)
8 (2)
225 (96)
5 (2)
4 (1)
0.0001
376 (56)
301 (44)
195 (45)
247 (55)
181 (78)
54 (22)
0.000
358 (53)
315 (47)
243 (55)
197 (45)
115 (49)
118 (51)
0.13
64 (11)
221 (32)
344 (50)
48 (8)
47 (13)
139 (31)
226 (49)
30 (7)
17 (8)
82 (33)
118 (51)
18 (8)
0.34
277 (41)
148 (22)
117 (17)
72 (10)
63 (9)
175
101
76
50
40
(40)
(23)
(16)
(11)
(10)
102 (44)
47 (20)
41 (18)
22 (9)
23 (9)
0.84
87 (12)
269 (42)
321 (46)
55 (11)
179 (43)
208 (45)
32 (12)
90 (41)
113 (47)
0.82
138 (21)
27 (4)
415 (61)
97 (14)
94 (22)
21 (4)
266 (60)
61 (13)
44 (19)
6 (3)
149 (63)
36 (15)
0.63
412 (60)
262 (40)
223 (49)
217 (51)
189 (80)
45 (20)
0.0001
537 (78)
144 (22)
336 (76)
106 (24)
198 (84)
37 (16)
0.02
94 (15)
580 (85)
57 (14)
385 (86)
37 (17)
195 (83)
0.35
29 (5)
645 (95)
17 (4)
425 (96)
12 (6)
220 (94)
0.40
205 (31)
472 (69)
171 (40)
271 (60)
34 (14)
201 (86)
0.000
262 (39)
415 (61)
156 (36)
286 (64)
106 (46)
129 (54)
0.02
463 (69)
213 (31)
321 (73)
121 (27)
142 (60)
92 (40)
0.002
P
N ¼ 681, for there are some unknown data refering to different questions:
a
673.
b
674.
c
675.
d
676.
e
677.
were cohabiting (whether married or not), compared with
single respondents. Similarly, both bereavement associated
with violence and an inadequate understanding of AIDS
treatability were associated with a lack of condom use in
both univariate and multivariate models. Age of first sex
(from 9 to 16 years old) and alcohol use emerged as being
S45
S46
Table 2. Factors associated with lack of condom use at last sexual intercourse when partners were steady among young people (aged 15–24
years) who were sexually active in the previous 12 months, Brazil, 2003.
Condom use n (%)
Variable
Yes
Age (years)
15–17
40 (63)
18–20
94 (51)
21–24
89 (45)
Marital statusa
Single
181 (69)
37 (22)
Widowed/divorced
5 (63)
Sex
Male
129 (63)
Female
94 (38)
Years of schooling
12 or more
20 (65)
0–4
14 (29)
5–8
58 (42)
9–11
131 (57)
Per capita income ( minimum wage)
Unknown
25 (63)
0–0.5
88 (49)
0.5–1
46 (44)
1 or more
64 (49)
Employment
Working
99 (53)
Never worked
20 (32)
Seeking a job
104 (50)
Adequate understanding regarding AIDS treatabilitya
Yes
152 (54)
No
71 (41)
Parenthood
Yes
174 (63)
No
49 (29)
Sex roles
Men should be more sexually experienced than women
Agree
156 (54)
Disagree
67 (41)
Alcohol use
No
58 (27)
Yes
159 (73)
Cocaine use
No
217 (97)
Yes
6 (3)
Marijuana use
No
200 (88)
Yes
23 (12)
Psychological violence
No
154 (53)
Yes
69 (43)
Lost someone close as a result of violence
No
123 (55)
Yes
100 (44)
No
OR (95% CI)
P
Adjusted OR (95% CI)
P
19 (37)
88 (49)
110 (55)
1.0
1.7 (0.9–3.2)
2.1 (1.1–4.0)
–
0.12
0.02
1.0
1.7 (0.8–3.3)
1.4 (0.7–3.0)
–
0.14
0.35
77 (31)
136 (78)
3 (37)
1.0
7.9 (4.9–12.6)
1.3 (0.3–5.5)
–
0.000
0.8
1.0
4.8 (2.6–8.9)
0.7 (0.2–2.8)
–
0.000
0.6
65 (37)
152 (62)
1.0
2.7 (1.8–4.2)
–
0.000
1.0
1.8 (1.1–3.1)
–
0.03
10
32
80
95
(35)
(71)
(58)
(43)
1.0
4.5 (1.6–12.7)
2.6 (1.1–6.2)
1.4 (0.6–3.3)
–
0.005
0.03
0.42
1.0
4.3 (1.2–15.8)
2.0 (0.6–6.1)
1.5 (0.5–4.4)
–
0.03
0.23
0.41
15
86
54
62
(37)
(51)
(56)
(51)
1.0
1.8 (0.8–3.8)
2.1 (1.0–4.8)
1.8 (0.8–3.8)
–
0.13
0.06
0.12
1.0
0.9 (0.3–2.4)
1.8 (0.7–4.8)
2.7 (1.0–7.2)
–
0.85
0.24
0.04
78 (47)
35 (68)
104 (50)
1.0
2.4 (1.3–4.8)
1.1 (0.7–1.8)
–1.0
0.008
0.51
–
2.4 (1.1–5.2)
1.0 (0.5–1.7)
0.03
0.88
126 (46)
90 (59)
1.0
1.7 (1.1–2.5)
–
0.014
1.0
1.6 (0.9–2.6)
–
0.08
96 (37)
121 (61)
1.0
4.2 (2.6–6.1)
–
0.000
1.0
1.7 (0.9–3.3)
–
0.09
136 (46)
81 (59)
1.0
1.7 (1.1–2.6)
–
0.013
1.0
1.3 (0.8–2.2)
–
0.28
48 (22)
175 (78)
1.0
0.7 (0.5–1.2)
–
0.23
–
–
–
–
207 (95)
10 (5)
1.0
0.6 (0.2–1.6)
–
0.48
–
–
–
–
185 (85)
32 (15)
1.0
0.8 (0.42–1.4)
–
0.39
–
–
–
–
133 (47)
84 (57)
1.0
1.4 (0.95–2.2)
–
0.08
1.0
1.1 (0.9–1.3)
–
0.27
93 (45)
124 (56)
1.0
1.6 (1.1–2.3)
–
0.025
1.0
1.6 (0.96–2.7)
–
0.07
CI, Confidence interval; OR, odds ratio.
a
n ¼ 439.
associated only in the multivariate model. In contrast,
having experienced psychological abuse was not retained
in the multivariate analysis. Cocaine and marijuana use was
not associated with a lack of condom use.
Brazilian youth. The 60% level of condom use presented
herein is higher than the 40% reported by Pimenta et al.
[6] in a study assessing condom use by young people in
Brazil and conducted in the second half of the 1990s,
although using different methodologies.
Discussion
Findings from previous national studies involving the
general population indicated a higher use by youth than
by adults [4,5]. One has to take into account that
methodological diversity may explain these differences.
In this study, we identified fairly high condom use at last
sexual intercourse within the past 12 months among
Table 3. Factors associated with lack of condom use at last sexual intercourse when partners were ‘casual’ among young people (aged 15–24
years) who were sexually active in the previous 12 months, Brazil, 2003.
Condom use n (%)
Variables
Yes
No
OR (95% CI)
P
Adjusted OR (95% CI)
P
42 (19)
3 (73)
0 (0)
1.0
11.4 (1.7–77)
–
–
0.013
–
1.0
15.3 (2.1–113.3)
–
–
0.008
–
2
6
20
17
(10)
(39)
(26)
(15)
1.0
5.6 (0.8–39.6)
3.1 (0.6–17.1)
1.5 (0.3–8.3)
–
0.08
0.18
0.61
1.0
2.1 (0.2–18.2)
1.0 (0.2–5.4)
0.8 (0.2–3.8)
–
0.49
0.98
0.81
7
12
1
25
(16)
(33)
(10)
(17)
1.0
2.5 (0.8–7.8)
0.6 (0.1–6.2)
1.0 (0.4–2.9)
–
0.11
0.65
0.92
1.0
2.9 (0.7–11.6)
0.1 (0.01–1.2)
1.4 (0.4–4.3)
–
0.19
0.98
0.60
3 (9)
13 (18)
27 (19)
2 (28)
1.0
3.9 (0.9–14.2)
2.4 (0.6–9.0)
3.8 (0.5–30.1)
–
0.06
0.20
0.20
1.0
4.9 (1.1–22.7)
3.9 (1.0–15.4)
7.50 (0.8–72.8)
–
0.04
0.05
0.08
22 (15)
23 (32)
1.0
2.7 (1.3–5.6)
–
0.007
1.0
5.6 (2.3–14.1)
–
0.0001
35 (92)
43 (22)
1.0
3.5 (0.7–16.5)
–
0.12
1.0
14.9 (1.9–114.4)
–
43 (95)
2 (5)
1.0
0.8 (1.7–4.1)
–
0.8
1.0
–
–
–
33 (18)
12 (31)
1.0
2.1 (0.9–4.8)
–
0.10
1.0
1.9 (0.6–5.7)
–
0.24
22 (15)
23 (29)
1.0
2.3 (1.1–4.8)
–
0.02
1.0
1.2 (0.9–1.6)
–
0.33
17 (12)
28 (30)
1.0
3.1 (1.5–6.5)
–
0.002
1.0
4.0 (1.5–10.5)
–
0.006
a
Marital status
Single
182 (81)
2 (27)
Widowed/divorced
4 (100)
Years of education
12 or above
16 (90)
0–4
11 (61)
5–8
61 (74)
9–11
101 (85)
Religion
Others
29 (84)
Protestant/evangelical
32 (67)
Spiritism/Umbanda/Candomblé
5 (90)
Catholic
123 (83)
Age at onset of sexual activity (years)
17–18
29 (91)
9–13
34 (72)
14–16
121 (81)
19–24
5 (72)
Adequate understanding regarding AIDS treatability
Yes
138 (85)
No
51 (68)
Use of alcohol
No
2 (8)
Yes
154 (78)
Use of cocaine
No
176 (94)
Yes
10 (6)
Use of marijuanab
No
161 (82)
Yes
25 (69)
Psychological violence
No
125 (85)
Yes
64 (71)
a
Lost someone close as a result of violence
No
113 (88)
Yes
75 (70)
a
n ¼ 233.
b
n ¼ 231.
The CEBRAP study assessed consistency in condom use
in conjunction with condom use within the past 12
months [5], and Paiva et al. [4] evaluated only consistency
in use.
The level of condom use identified in our study is
comparable with that described in studies involving
young people in developed countries, and is higher than
indicated in studies conducted in other developing
countries [1,11,13,20]. These high percentages can be
explained by the fact that this generation initiated their
sexual life under the aegis of AIDS awareness programmes, which is consistent with previous studies
[21,22]. This seems to be particularly relevant in view of
studies indicating that condom use during sexual
initiation is correlated with their subsequent use [1].
However, it should be noted that, among studies carried
out in developed countries, we found none that involved
representative samples of the general population of youth,
only students.
The promotion of condom use is central to the Brazilian
programme to counter the HIV/AIDS epidemic [4,23,
24], and young people assessed in the present study
represent a priority population for this programme [25–
28]. Therefore, our results support a trend towards
increased condom use by young people, consistent with
other studies [13,29]. However, only periodical national
studies may confirm this hypothesis.
Although the results of several studies have indicated the
need to examine condom use in relation to the type of sex
partner, a standardized approach has yet to be developed
for this purpose [1,11–13,30,31]. In the present study, we
decided to employ self-reported categorization, and,
unlike other national studies [4,5], we established no
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S48
specific parameters for the definition of steady and casual
relationships. The purpose was to highlight the role of
personal views about partners in defining condom use
patterns. These methodological differences, in conjunction with the distinction between the two approaches
utilized in measuring condom use (at last sexual intercourse versus consistent use over a certain period of
time), constitute significant limitations when comparing
surveys. There is, however, some comparability because
condom use at last sexual intercourse has been considered
a reliable proxy in prospective studies [20,30,32].
The assessment of condom use is complex. The fact that
the data in the present survey refer to the last sexual
encounter might be viewed as a limitation. Some authors
suggest the need to assess consistent condom use rather
than simply determining condom use at last sexual
intercourse [33,34]. Other authors have reported retrospective narrative accounts of last sexual intercourse as a
proxy of future condom use [30,32].
The differences found among young people based on
the type of relationship (more women and higher mean
age among those in steady relationships; more men
among those in casual relationships) are consistent with
the findings of Paiva et al. [4]. Data obtained by these
authors differ from those collected in the present study
in terms of the level of education. In our study, we
identified no significant differences in years of schooling
between the steady and the casual partner groups, whereas
Paiva et al. [4] found that those in steady relationships
tended to have lower levels of education than did those
in casual relationships. This discrepancy might be
associated with the fact that we only studied the young
population, which presents higher and more homogeneous levels of education than do other age groups in
Brazil [35].
We identified a significant difference in condom use
among young people according to the type of partnership
at last sexual intercourse, being more frequent with casual
partners than with steady partners. The results of some
national studies have indicated significant differences in
condom use according to whether the sexual partner is
steady or casual [4,5]. Differences in condom use in
relation to the type of partner expressed as odds ratios
(OR), were identified in a study involving army recruits,
being more frequent with commercial partners, paid (OR
1.7) or paying (OR 1.4), and with casual partners (OR
1.3) than with steady partners. In a study involving the
sexually active Brazilian population [4], condom use
during sexual intercourse with casual partners was found
to be four times more frequent than its use with steady
partners.
The differences between the two sex partner groups
(steady and casual) regarding factors associated with the
lack of condom use at last intercourse seem to be
coincident with some aspects of vulnerability to AIDS
previously identified in Brazil and in other developing
countries. In such contexts, where a pattern of heterosexual transmission and a trend towards the feminization
of the AIDS epidemic are emerging [36,37], the population of poorly educated or unemployed women who have
few sexual partners during their lives plays an important
role in the epidemiological profile, as a result of their
economic dependency on their sexual partners and lack of
power in negotiating condom use. However, this study
also showed that a per capita family income above one
minimum wage posed an independent risk when
schooling had been taken into account, suggesting that
schooling and income play separate and diverging roles in
this model, rather than converging in a more traditional
construct of social class.
Studies carried out in these contexts indicate difficulties
in the incorporation of condom use, especially within
steady relationships. This occurs because these relationships apparently present a lower perceived infection risk,
which may actually reflect reality. However, even when
there is a perception of risk, proposing condom use
within the context of supposedly monogamous and truly
hierarchical relationships may signal a lack of trust
between partners, and jeopardizes the relationship to the
extent that the social contract of marriage implies in the
assumption of fidelity [2,11,31,38]. In addition, several
authors have stressed the fact that contraception is the
primary concern among individuals, especially women,
involved in steady relationships. In such cases, women
adopt contraceptive methods that are considered to be
more effective, to the detriment of condom use [13].
Moreover, condom use should be discussed in a context
of an open and mutual exchange of knowledge about the
partners’ serostatus.
Among those in the casual partner group, factors
correlated with the lack of condom use were cohabitation, age of first sex at 9–16 years of age, a positive history
of alcohol use, inadequate understanding about AIDS
treatability, and bereavement associated with violence.
The fact that individuals who used to cohabit report
lower condom use in their intercourses with casual
partners might be interpreted in two ways. First, these
individuals might be generally different from single
individuals who have more readily incorporated condom
use with casual partners. Second, it might reveal that they
are relating to their casual partners using a condomrelated norm acceptable with ‘steady’ partners.
Among those in the steady partner group, it is likely that
living in contexts of less exposure and, more importantly,
cohabitation lead to less incorporation of the habit of
condom use because it competes with other contraceptive
methods and involves the question of trust and serostatus
awareness.
In our study we found an association between the
initiation of sexual life at 9–16 years of age and the lack of
condom use among those in the casual partner group.
Some studies have demonstrated this association between
the earlier age of first sex and the lack of condom use
[21,22,39,40]. It is possible to consider that at earlier ages,
youth found more obstacles to negotiate condom use.
This finding supports the importance of early condom use
to establish a pattern of condom use forward to
subsequent sexual activity [1,21,22,39].
In contrast to the steady partner group, alcohol plays
an important role as a determinant of the lack of condom
use in the casual partner group. Research has shown
an association between alcohol use and risky sexual
behaviour in adolescents, such as condom non-use
[1,12,20,40–45]. Considering our findings, in conjunction with the Brazilian literature on young people’s sexual
behaviour and AIDS prevention, it is plausible to think
that alcohol has been used as a disinhibition strategy. The
literature reports the use of alcohol by young men in
dating contexts as a strategy to reduce the inhibition
caused by the social pressures on male sexual behaviour
[46,47].
This seems to be particularly relevant in view of studies
indicating the high prevalence of alcohol use in life by
youth in Brazil: 48% among young people aged 12–17
years and 73.2% among young people aged 18–24 years,
in a nationwide household survey [48], and 86.8% in two
school-based surveys, in two different capitals from the
southern region of the country [49,50].
It is important to note, however, that our study measured
alcohol use in life; it did not investigate the influence of
alcohol use in the last sexual intercourse, nor did it analyse
data on the frequency of alcohol use.
With regard to knowledge about AIDS and treatment
effectiveness, we found that adequate knowledge increased the levels of condom use. Despite the wide dissemination of information concerning AIDS, it is worthwhile
bolstering information programmes in Brazil, highlighting the potentials and limitations of antiretroviral
therapy.
In this study, a lack of condom use was associated with
bereavement as a result of violence. Living under
conditions of impending risks to survival on an everyday
basis could represent an obstacle with respect to the
adoption of HIV protective practices [51].
In conclusion, this nationwide study provides additional
evidence of differences in the determinants of condom
use according to whether partners are ‘steady’ or ‘casual’.
Prevention policies and programmes should develop
strategies responsive to such diverse contexts of sexual
partnerships.
Acknowledgements
The authors would like to thank the Instituto Cidadania
(Citizenship Institute), the coordinators of the Projeto
Juventude (Youth Project) and Criterium Assessoria em
Pesquisas (Criterium Research Assistance) for having
allowed us to utilize data from the ‘Perfil da Juventude
Brasileira’ (Brazilian Youth Profile) study in order to
produce this article. They would also like to thank Mrs
Rita Dias for her effort in explaining the methodological
aspects involved on the study design.
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34; 1999. pp. 249–268.
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UNIFESP – Universidade Federal de São Paulo; 2002.
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performance among teenagers. Rev Saúde Pública 2001; 35:
150–158.
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among incarcerated teenagers, Brazil. Rev Saúde Pública 2002;
36:76–81.
Knowledge, practices and behaviours related to
HIV transmission among the Brazilian population in
the 15–54 years age group, 2004
Célia Landmann Szwarcwalda, Aristides Barbosa-Júniorb,
Ana Roberta Pascomb and Paulo Roberto de Souza-Júniora
Objective: To describe transmission vulnerability for acquiring HIV infection among
the Brazilian population aged 15–54 years.
Design: A population-based survey.
Methods: Sampling was stratified by geographical region. A total of 6006 interviews
were conducted. Indicators of knowledge and sexual practices and the relative sizes of
the vulnerable subgroups were estimated. Logistic regression analysis was used to
determine the main factors associated with safe sex practices.
Results: Regarding knowledge indicators in the age group 15–24 years, a high
percentage (91%) spontaneously cited sexual intercourse as a form of HIV transmission,
and 62% had correct knowledge of the modes of HIV transmission (five correct items).
The proportion of consistent condom use with casual partners was 52%, increasing to
59% in the youngest age group. Higher proportions of inconsistent condom use with
any kind of partner were found among women and among the poorest. A multiplicity of
sexual partners, low socio-economic status and cocaine use were important predictors
of unprotected sex among men living without a companion. Among individuals aged
15–49 years, 0.2% currently inject cocaine, 4.6% of the men paid for sex at least once
over the past year and 1.0% of the women were paid in exchange for sex. Among
sexually active men of the same age group, 3.5% reported sexual relations with
other men.
Conclusion: Besides the need to establish the role exercised by the vulnerable subgroups in the HIV transmission dynamics, results indicate that it is necessary to
investigate unsafe sexual practices further among the poorer sectors of society.
AIDS 2005, 19 (suppl 4):S51–S58
Keywords: Brazil, HIV risk practices, knowledge, nationwide survey,
socio-economic inequalities, vulnerable groups
Introduction
The HIV/AIDS epidemic began in Brazil in the early
1980s. Throughout these years, the epidemic has been
concentrated, with an HIV infection prevalence rate
among the general population of less than 1% [1]. Higher
prevalence rates were recorded among the most vulnerable subgroups for HIV infection, including men who
have sex with men (MSM) and injection drug users
(IDU), who appear to be among the earliest to be affected
[2].
Currently, heterosexual transmission is playing an important role in the spread of the epidemic. Over the past few
years, AIDS incidence has evolved more slowly among
MSM and IDU, but has increased steeply among the
heterosexual population, especially among individuals
with low educational levels [3] and of lesser socioeconomic status [4].
The various measures that are being adopted to
prevent the spread of HIV in Brazil are based upon the
natural history of the infection, on the experience of
From the aDepartment of Information on Health (DIS/CICT), Oswaldo Cruz Foundation, Brazil, and the bNational STD/AIDS
Program, Brazilian Ministry of Health, Brazil.
Correspondence to Célia Landmann Szwarcwald, DIS/CICT/FIOCRUZ, Av Brazil, 4365, RJ 21045-900, Brazil.
E-mail: [email protected]
S51
S52
international AIDS programmes, and on the results of
data analyses seeking to explain the dynamic of the
transmission of the disease [5].
Studies describing sexual risk behaviours and levels of
vulnerability provide valuable information in designing
the best strategies for controlling the spread of HIV. Early
monitoring initiatives were undertaken in Brazil during
the 1990s, which provide sources of data of targeted HIV
infection risk behaviours. Pioneering research conducted
among Brazilian Army conscripts began in 1996 as part of
a technical co-operation project between the Ministry of
Health and the Brazilian Army. This partnership resulted
in a number of behavioural and seroprevalence studies
among military conscripts at the time of enlistment.
Conducted on an annual basis from 1996 to 2000, and
followed through in 2002, these surveys focused on
different themes each year, with the aim of improving
knowledge about the sexual practices of young Brazilian
men [6].
The National Demography and Health Survey [7],
carried out in 1996, involving a module on sexual
behaviour and knowledge about HIV transmission,
constituted a further example of this type of research.
In 1998, another nationwide survey was carried out by
the Brazilian Center of Analysis and Planning [8] with the
objective of identifying representations, behaviour,
attitudes and sexual practices of the Brazilian population.
In 2004, this national population-based study was
designed to investigate knowledge and vulnerability
behaviours related to HIV infection among Brazilians
aged 15–54 years. Taking into account that the last survey
providing national data on practices and behaviours
related to HIV transmission was carried out in 1998, this
investigation provided recent data at the national level to
determine programme effectiveness and a description of
the current sociobehavioural trends driving the epidemic
in Brazil.
Methods
The project was submitted to the Research Ethics
Committee of the Oswaldo Cruz Foundation and was
approved in July 2004 (protocol 243/04).
Brazil has an area of 8.5 million square kilometres, with a
population of approximately 170 million inhabitants. The
country is politically and geographically divided into
five distinct macroregions; each has its own physical,
demographic and socio-economic aspects. The north and
the north-east have the lowest socio-economic development. The south-east region is the most important region
economically and concentrates 44% of the total Brazilian
population.
The sample size was established at 6000 individuals
between 15 and 54 years of age. The sample was stratified
by geographical macroregion: 900 interviews were conducted in the north, 1100 in the north-east, 2200 in the
south-east, 900 in the south and 900 in the centre west. In
each of the geographical regions, a three-stage sampling
was used by state, census tract and household.
All Brazilian states were included in the sample. The
number of interviews in each state was established by the
total number of interviews in each geographical region,
proportional to the number of inhabitants in each state in
relation to the total region population.
In each state, tracts were selected by systematic sampling
with a probability proportional to size. In each census
tract, seven households were chosen so that the number of
tracts in each state was determined by the total number
of interviews in the state divided by seven. In each
household only one person was selected for interview.
The questionnaire was modular, consisted of the following sections: sociodemographic conditions; knowledge
about HIV transmission; prevention and control of
sexually transmitted diseases; HIV testing; use of licit and
illicit drugs; and sexual practices. Considering that some
questions and topics approached could cause embarrassment or lead to refusals or false information, the modules
relating to the use of drugs and sexual practices were selfcompleted by the interviewees in order to ensure reliable
responses. The self-reported part was done on a separate
sheet, and deposited directly in an urn, as a way of
guaranteeing confidentiality for the interviewee.
This analysis focused on knowledge of HIV transmission,
sexual practices, and vulnerable subgroups. The data were
weighted in accordance with the sample design and
SUDAAN software [9] was used to perform the statistical
analysis.
For knowledge indicators, we considered the percentage
of individuals spontaneously citing sexual intercourse as a
form of HIV transmission and three other indicators that
are monitored internationally in order to achieve the
‘millennium goals’ in the fight against HIVand AIDS [10],
including: (i) the percentage that knows that consistent
condom use is a way of protection from HIV infection; (ii)
the percentage that agrees that an apparently healthy
individual can be infected with HIV; and (iii) the percentage with correct knowledge about the forms of HIV
transmission, established by answering five questions correctly (not transmitted by insect bites; not transmitted by
the use of public toilets; not transmitted by sharing cutlery,
glasses or meals; can be transmitted during intercourse
without a condom; can be transmitted by needle-sharing).
Sexual activity was measured using the following indicators: the percentage of sexually active individuals (over
HIV transmission among 15–54-year-old Brazilians Szwarcwald et al.
lifetime and over the past 12 months); the percentage
of individuals with a sexual debut at under 15 years old;
the percentage of individuals with 10 or more partners
over their lifetime; the percentage of individuals with five
or more casual partners over the past 12 months.
Regarding protected sexual practices, the following
indicators were used: condom use at last intercourse
(with any type of partner and with a casual partner) and
consistent condom use (with a fixed partner, with a casual
partner, and with any type of partner). The latter was
established on the basis of the reporting of condom use in
all sexual intercourses.
To measure socio-economic status and test for socioeconomic inequalities, a combination of educational
level (did not complete high school; completed high
school) and the number of household assets (television,
video player/recorder, radio, refrigerator, freezer, washing machine, dish-washing machine, fixed telephone,
cellular phone and automobile) was used. Three socioeconomic status categories were established: A, individuals with six or more household assets who had
completed high school; C, individuals with less than
six household assets and incomplete high school; and B,
composed from all the other individuals.
Furthermore, the survey data provided an opportunity
to determine subpopulation sizes of the following vulnerable groups: MSM; IDU; female commercial sex
workers; and male clients of female sex workers. These
responses were obtained in the self-completed part of the
questionnaire.
In order to obtain data about sexual orientation, the
participants were asked if they normally have sexual
intercourse: only with men; only with women; more
frequently with men but sometimes with women; more
frequently with women but occasionally with men. The
group of female commercial sex workers was defined by a
positive response to the question ‘During the last twelve
months has a casual partner paid you or given you presents
in exchange for sex?’ among women. The group of clients
of sex workers was established by a positive response to the
question ‘During the last twelve months have you paid a
casual partner to have sex?’ among men.
In relation to the use of illicit drugs, the uses of snorted
and injected cocaine were considered (currently and over
lifetime). The participants were asked if they: ‘have never
used’; ‘have tried but have not continued to do so’; ‘use it
occasionally’; or ‘frequently use’.
In order to establish the main factors associated with
protected sex, a multivariate logistic regression analysis
was performed among sexually active individuals, stratifying by sex and conjugal status. Stepwise logistic regression
models were used considering consistent condom use
with any type of partner as the response variable and the
indicators of sexual activity, age, socio-economic class and
cocaine use as the independent variables.
Results
Of a total of 6700 visited households, 6006 questionnaires
were analysed. Despite repeated visits, 8.4% were not
at home and 2.1% refused to participate. In each
geographical region, the sample distribution by age and
sex was compared with the 2000 Demographic Census
population distribution and very small percentage differences (less than 1%) were found. In what follows, we
present the main results organized by the topic considered
in the analysis.
Knowledge about HIV transmission
The results concerning knowledge about HIV transmission in the age group 15–24 years (presented in
Table 1) showed that a high percentage (91%) spontaneously cited sexual intercourse as a form of HIV
transmission; 95% knew that regular condom use is a way
of protection against HIV; and 91% agreed that an
apparently healthy individual can be infected with HIV.
Of those individuals who had completed elementary
education the percentages were greater than 95%.
Table 1. Indicators of knowledge about HIV transmission by educational level among individuals aged 15–24 years, Brazil, 2004.
Educational level
Indicator
Percentage
Spontaneously citing sexual intercourse as a form of HIV transmission
That knows that condom use is a form of protection against HIV
That agrees that an apparently healthy person can be infected with HIV
With correct knowledge about HIV transmission (correct answers in all items below)
That knows that HIV is not transmitted by insect bites
That knows that HIV is not transmitted by the use of public toilets
That knows that HIV is not transmitted by sharing cutlery, glasses and meals
That knows that HIV can be transmitted by needle-sharing
That knows that HIV can be transmitted by sexual intercourse without a condom
Incomplete
high school
Complete
high school
Total
87.3
93.1
88.6
51.3
94.1
80.0
78.1
81.0
96.1
96.4
97.9
95.5
78.8
97.1
90.7
92.8
96.7
96.7
91.0
95.0
91.4
62.3
95.3
84.3
84.0
87.3
96.4
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Table 2. Indicators of sexual behaviour by sex and age group, Brazil, 2004.
Age group (years)
Group
Indicator
Total sample
Sexually active individuals over lifetime (%)
Sexually active individuals over past year (%)
Sexually active over
lifetime
Mean age of sexual debut
With 10 or more partners over lifetime (%)
Sexually active during year before survey
With five or more casual partners over past year (%)
Condom use (%)
At last intercourse
At last intercourse with casual partner
Always with fixed partners
Always with casual partners
Always with any type of partner
Regarding the indicator of correct knowledge monitored
internationally by the United Nations Special Assembly
Session on HIV/AIDS (UNGASS) and established on
the basis of five correct answers about HIV transmission,
62% of the participants demonstrated correct knowledge.
A large variation was also found by the level of educational attainment: the percentage with correct knowledge
ranged from 51% in the group with incomplete education to 79% among those who had completed high
school.
Sexual practices
The results presented in Table 2 showed that approximately 90% of the population between 15 and 54 years of
age was sexually active and 81% had been sexually active
for the past 12 months. Almost 20% of the participants
reported more than 10 partners over their lifetime. The
mean age of sexual debut among participants aged 25–39
was 16.9 years, beginning sexual activity approximately
10 months earlier than those in the oldest group. The
highest percentage of multiplicity of partners over the past
12 months was found among the youngest age group
(15–24 years old): 7% reported five or more casual
partners in the previous year (Table 2). The multiplicity of
sex partners (over lifetime or past year) is a typical male
practice. Among women, the percentage of five and more
Sex
15–24
25–39
40–54
Total
M
F
T
M
F
T
M
F
T
M
F
T
M
F
T
81.0
66.8
73.9
71.0
61.8
66.4
14.8
15.9
15.3
26.0
4.6
16.2
11.3
1.7
6.7
98.0
96.5
97.2
92.9
89.3
91.1
15.8
17.9
16.9
35.2
5.0
19.8
5.4
0.6
3.0
99.0
97.2
98.1
93.5
80.4
86.7
16.0
19.2
17.7
41.6
2.8
21.4
5.0
0.7
2.9
92.3
86.7
89.5
85.4
77.7
81.4
15.5
17.8
16.7
34.2
4.2
19.3
7.0
0.9
4.0
M
F
T
M
F
T
M
F
T
M
F
T
M
F
T
67.2
43.7
56.2
78.6
63.9
74.1
46.3
31.5
38.8
64.3
45.1
58.4
46.8
30.0
39.0
38.9
32.3
35.6
72.4
56.1
66.5
22.7
21.1
21.9
52.8
41.5
48.7
23.4
20.6
22.0
24.1
20.0
22.2
52.3
48.8
51.2
17.2
14.9
16.2
46.0
32.2
41.5
18.4
13.5
16.1
42.8
32.0
37.6
71.3
58.1
67.0
27.6
22.2
24.9
56.6
41.3
51.5
28.9
21.4
25.3
casual partners in the previous year was very small, less
than 1%.
With regard to self-reported safe sexual practices, individuals aged 15–24 years used condoms more frequently
than the other age groups, especially with casual partners:
74% reported condom use in the last sexual intercourse
and 59% reported consistent condom use over the past
year with this type of partner. In the total sample, the
percentage of consistent condom use with casual partners
was 52%, varying from 57% among men to 41% among
women. The percentage of regular condom use with any
type of partner was low, 29%, and there were similar
noteworthy sex differentials (Table 2).
The association between indicators related to condom use
and socio-economic status was examined in Table 3.
Considering all age groups together, statistically significant differences by socio-economic class were evidenced
for all indicators, and invariably unfavourable in the
poorest class (Table 3). Consistent condom use with a
casual partner varied from 61% in the best socio-economic
group to 47% among the less well-off, and consistent
condom use with any type of partner ranged from 32%
(class A) to 19% (class C). The smallest differences were
found in the oldest age group (40–54 years old).
Table 3. Indicators of condom use between sexually active individuals over past year by age group and socio-economic class, Brazil, 2004.
Socio-economic classa
Indicator
Condom use (%)
At last intercourse
At last intercourse with casual partner
Always with fixed partners
Always with casual partners
Always with any type of partner
Age group (years)
A
B
C
Total
P valueb
15–24
25–39
40–54
T
15–24
25–39
40–54
T
15–24
25–39
40–54
T
15–24
25–39
40–54
T
15–24
25–39
40–54
T
62.0
39.6
32.3
44.7
82.9
71.0
50.8
73.4
42.8
28.1
23.0
31.1
66.3
58.1
52.7
61.1
43.4
28.0
24.6
32.0
60.6
39.8
22.7
39.5
73.9
66.2
50.0
66.2
43.4
25.4
16.3
27.2
56.8
48.1
40.9
49.9
43.2
26.8
13.9
27.6
52.2
32.3
17.0
33.7
67.7
63.6
52.7
63.4
33.0
14.8
12.2
19.1
54.1
42.8
37.4
46.5
32.8
14.5
13.2
19.4
57.3
36.6
22.4
38.4
74.0
66.6
51.2
66.9
38.8
21.9
16.2
24.9
58.5
48.7
41.9
51.5
39.0
22.0
16.1
25.3
0.003
0.002
0.000
0.000
0.001
NS
NS
0.003
0.003
0.000
0.001
0.000
0.036
0.012
NS
0.000
0.002
0.000
0.000
0.000
a
Established by a combination of number of household assets and educational level (A, more than six assets and complete high school; C, less than
six assets and incomplete high school; and B, all others).
b
Significance level of the heterogeneity test of proportions by socio-economic class in each age group.
Vulnerable subgroups
By means of targeted survey questions, it was possible to
estimate the relative size of vulnerable groups (Table 4).
Among male respondents aged 15–49 years old, 3.2%
reported having had sex with other men (3.5% among
sexually active men, 2% with men only, and 1.5% with
both men and women).
her presents in exchange for sex over the past year (1.4%
among past year sexually active women). Of the 2486
men aged 15–49 years, 4.6% had paid at least one casual
partner for sex within the previous 12 months (5.5%
among past year sexually active men).
Regarding the use of illicit drugs among 15–49-year-old
respondents, 5.2% had already snorted cocaine at least
once in their lives: 8.2% among men and 2.5% among
women. As for the use of injected cocaine, 0.9% reported
Of the 2571 women aged 15–49 years, 1.0% reported at
least one casual partner who either had paid or had given
Table 4. Size estimates (relative and absolute) of vulnerable subgroups in the population aged 15–49 years, Brazil, 2004.
Vulnerable group
Female CSW
Male clients of CSW
Men who have sex with men
Injected cocaine
At least once
Current use
Snorted cocaine
At least once
Current use
Sex
Relative size (%)
95% CI
Estimated size
(Brazilian population
aged 15–49 years)
F
M
M
1.0
4.6
3.2
0.58–1.42
3.71–5.49
2.37–4.03
495 832
2 211 768
1 538 621
M
F
T
M
F
T
1.3
0.5
0.9
0.3
0.2
0.2
0.80–1.80
0.21–0.79
0.62–1.18
0.03–0.57
0.01–0.39
0.04–0.36
625 065
247 916
878 986
144 246
99 166
195 330
M
F
T
M
F
T
8.2
2.5
5.2
1.7
0.3
0.9
7.04–9.36
1.88–3.12
4.53–5.87
1.18–2.22
0.10–0.50
0.63–1.17
3 942 716
1 239 580
5 078 586
817 392
148 750
878 986
CI, Confidence interval; CSW, commercial sex workers.
S55
S56
Table 5. Factors associated with consistent condom use: results of multivariate logistic regression models according to conjugal status and sex.
Variables included in the model
Men without companion
A
B
C
10 or more sexual partners over lifetime
Yes
No
Snorts or used to snort cocaine
Yes
No
Men with companion
Age
A
B
C
Women without companion
Age
10 or more sexual partners over lifetime
Yes
No
Women with companion
Age
A
B
C
OR
95% CI
Adjusted OR
95% CI
1.00
1.25
0.68
–
0.87–1.79
0.49–0.95
1.00
1.23
0.63
–
0.85–1.78
0.45–0.90
0.53
1.00
0.39–0.71
–
0.55
1.00
0.41–0.74
–
0.38
1.00
0.22–0.66
–
0.42
1.00
0.23–0.74
–
0.97
0.96–0.99
0.97
0.95–0.98
1.00
0.66
0.49
–
0.45–0.96
0.34–0.72
1.00
0.66
0.46
–
0.85–1.78
0.31–0.67
0.98
0.96–0.99
0.98
0.96–0.99
0.46
1.00
0.23–0.92
–
0.49
1.00
0.24–0.99
–
0.97
0.96–0.99
0.97
0.95–0.98
1.00
0.84
0.42
–
0.57–1.24
0.28–0.62
1.00
0.86
0.40
–
0.58–1.26
0.27–0.60
a
Established by a combination of number of household assets and educational level (A, more than six assets and complete high school; C, less than
six assets and incomplete high school; and B, all others).
having injected cocaine at least once during their lives
(1.4% for men and 0.4% for women) whereas 0.2% are
currently users.
Factors associated with consistent condom use
The stepwise logistic regression results were analysed by
strata composed by conjugal status and sex (Table 5).
Among men without a companion, low socio-economic
level, a multiplicity of partners over their lifetime (10 or
more partners) and cocaine use were shown to be relevant
predictors of unsafe sex. Among women without a
companion, the statistical analysis showed that younger
women use condoms more frequently than the oldest,
and there was a significant association between multiple
partners over a lifetime (10 or more) and unsafe sex.
Among men and women living with a companion,
through the stepwise logistic regression model, it was
shown that the main factors associated with consistent
condom use are: to be young and to be from a higher
socio-economic level. The variables concerning multiplicity of partners over lifetime (10 or more partners) and
cocaine use did not show significant effects (Table 5).
Discussion
The implementation of programmes and strategies for
reducing vulnerability to HIV infection is among the
‘Declaration of Commitment’ goals subscribed to by
the countries at UNGASS, 2001. In order to evaluate the
effectiveness of the interventions, a group of indicators
was selected for the purpose of the international
monitoring of the HIV/AIDS epidemic.
With respect to knowledge indicators, Brazil is well
placed by comparison with other nations. Regarding the
percentage of individuals 15–24 years old who know that
condom use is a form of preventing HIV infection, the
estimate in Brazil of 95% is greater than the percentage in
Cuba (89%) and in Colombia (67%). As far as the
indicator of correct knowledge is concerned (five correct
answers), the Brazilian percentage among the youngest
age group (15–24 years old) was 62%, the highest percentage of all of the countries with available information.
For example, in Cuba the percentage answering correctly
was 52% and in India only 17% [10].
Regarding protected sex practices, international comparison shows results that are not as satisfactory as those
obtained for HIV transmission knowledge. Among young
people (15–24 years old), the percentage of consistent
condom use in Brazil (59%) is much higher than the
percentage found in Colombia (29%), is similar to that of
Mexico (57%) and India (59%), but much lower than the
percentage in France (72%) [10]. Moreover, previous
results from a nationwide survey carried out in 1998 [8]
evidence a trend towards stabilization (or even a slight
decrease among the youngest) in the frequency of consistent condom use.
In relation to sex differences in condom use, the findings
showed relevant differences in safe sexual practices and in
the reported number of partners, which may be a result of
the Brazilian female embarrassment at talking about sex.
Results of a study carried out in India [11] emphasized the
social role of women and the imbalance of power in
decision-making with respect to the circumstances in
which safe sex is practised. These constraints, particularly
found in developing countries, are an important obstacle
to the implementation of safe sex strategies and should be
faced through interventions targeted at empowering
women in negotiating safe sex [12].
Socio-economic differences were evidenced in various
aspects of this analysis, corroborating results that have
been found previously [13]. Knowledge and sexual
practice indicators showed that groups of lower socioeconomic status have the least information about forms of
HIV transmission and undertake unsafe sexual practices
more frequently, especially men and women living
without a companion.
However, it is worth noting that the survey design did not
allow the exploration of socio-economic inequalities in
unsafe sexual practices in depth, mainly those related
to social environment, known to influence individual
lifestyles and sexual behaviour [14]. A growing body of
international research has shown that structural and
environmental factors are relevant to promote the spread
of the HIV/AIDS epidemic [15], which were not assessed
in the present survey.
Among single men, the results of the multivariate
statistical model indicated that a multiplicity of partners
over the lifetime and cocaine use were significantly
associated with unsafe sex. Such findings confirm those
described in the specialized literature, such as the study
carried out in Thailand [16], which showed that young
people who use psychoactive substances systematically
incur greater risks of HIV infection, and point out the
synergy of risk factors, as discussed in the 1999 Brazilian
Army conscript study [17].
The epidemiology of HIV/AIDS has evidenced the
disproportionate contribution made by vulnerable groups
in the dynamics of the spread of the epidemic [18].
In addition to the increased vulnerability of certain
population groups such as MSM, IDU and commercial
sex workers, it has been demonstrated that the presence of
co-infection with a sexually transmitted disease, inconsistent condom use and sex with multiple partners are key
determinants in promoting HIV transmission [19].
Using the survey data, it was possible to estimate the
relative sizes of the subgroups vulnerable to HIV
infection. However, particular HIV risk behaviour within
the vulnerable groups could not be analysed because of
the small number of individuals in each group. Given the
population-based survey limitations, sampling procedures
specifically aimed at hard-to-reach population groups are
being developed or adapted to be used among us over the
next few years [20–22].
Information bias constitutes another limitation of this type
of study. Although the questionnaire modules relating to
the use of drugs and sexual practices were self-completed
as a way of reducing embarrassment at answering some
topics, low-educated individuals may have been unable to
respond coherently to the written questionnaires.
In conclusion, the HIV/AIDS epidemic in Brazil is
currently undergoing a transitional phase, disproportionately affecting women and lower socio-economic
groups [23,24]. It is plausible to argue that the current
dynamic of the Brazilian epidemic depends not only on
the role played by the most vulnerable groups, but also on
collective vulnerability factors (such as adverse social
conditions), which are gradually gaining more importance. Therefore, although there appears to be a need to
establish the role exercised by the vulnerable subgroups in
HIV transmission dynamics, especially commercial sex
workers and their clients who act as bridges for HIV
spreading among the heterosexual population [25], it is
also necessary to investigate risky practices and behaviours
related to HIV transmission further among the poorer
sectors of society.
Sponsorship: This work was supported by the Centers
for Disease Control and Prevention, Global AIDS
Program Brazil (CDC/GAP-Brazil).
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the study of hidden populations. Social Problems 1997; 44:174–
199.
21. McFarland W, Caceres CF. HIV surveillance among men
who have sex with men. AIDS 2001; 15 (Suppl. 3):S23–
S32.
22. Stueve A, O’Donnell LN, Duran R, San Doval A, Blome J. Time–
space sampling in minority communities: results with young
Latino men who have sex with men. Am J Public Health 2001;
91:922–926.
23. Castilho EA, Bastos FI, Scwarcwald CL, Fonseca MG. AIDS in
Brazil: a changing epidemic. Cadernos de Saúde Pública 2000;
16 (Suppl. 1):4–5.
24. Parker RE, Camargo KR Jr. Poverty and HIV/AIDS: anthropological and sociological aspects. Cad Saudé Pública 2000; 16
(Suppl. 1):89–102.
25. Ghys PD, Jenkins C, Pisani E. HIV surveillance among female
sex workers. AIDS 2001; 15 (Suppl. 3):S33–S40.
Factors associated with institutionalization of children
orphaned by AIDS in a population-based survey in
Porto Alegre, Brazil
Marlene Doringa,b, Ivan França Juniorb,c and Isete Maria Stellad
Background: There are increasing numbers of children orphaned by AIDS, especially
in countries without universal free AIDS treatment. As institutionalization is associated
with bad health and developmental outcomes, we have identified the factors associated
with the institutionalization of AIDS orphans in a population-based survey in a city in
southern Brazil.
Methods: Using AIDS mortality and healthcare registries from 1998 to 2001, a crosssectional study was conducted among the caregivers of children aged 0–14 years who
were the survivors of parents dying of AIDS in Porto Alegre. Data were collected by a
household survey using a structured questionnaire.
Results: Out of 1131 orphans identified, 75.4% of their caregivers participated. Among
participants, 70% had lost their father and 50% their mother, and 21% had lost both
parents. At the time of the survey, 41% of the children lived with the mother, 25% lived
with grandparents and 5% lived in institutions. In multivariate analysis, HIV positivity
multiplied the child’s chances of living in an institution by a factor of 4.6, losing its
mother by 5.9, losing both parents by 3.7, and having a non-white mother by 4.0.
Conclusion: This study provides population-based data on what has become of the
children of individuals dying of AIDS. Improving the quality of life and averting the
institutionalization of AIDS orphans requires interventions to promote the survival of
mothers living with AIDS, as well as specific interventions for child family placement.
Reducing the stigma of HIV infection in children and racial discrimination present
challenges in Brazil.
AIDS 2005, 19 (suppl 4):S59–S63
Keywords: AIDS, Brazil, orphans
Introduction
The numbers of children orphaned as a result of AIDS
will continue to increase over the next decade,
particularly in countries where there is no effective and
universal treatment for AIDS. Around the world, 14
million children have been orphaned by AIDS. The
majority of these children (82%) live in developing
countries; however, it is not known how many AIDS
orphans live in Brazil [1,2].
To June 2004, 362 364 cases of AIDS had been reported
in Brazil. In contrast to other regions of Brazil, the south
has the highest AIDS incidence, and has not experienced
the same decline in the number of AIDS deaths [3]. Porto
Alegre, where the present study was carried out, has
1 360 590 inhabitants and is the capital of Brazil’s
southernmost state [4]. According to the Ministry of
Health, the city’s AIDS incidence ranks third highest in
the country (90/100 000 inhabitants) [5].
Even though the majority of individuals living with HIV/
AIDS are adults, men and women at reproductive age, the
pandemic has severe detrimental effects on children and
adolescents [2]. Orphanhood, in particular, has implications for the children’s survival. Orphans may experience
From the aUniversity of Passo Fundo, State of Rio Grande do Sul, the bSchool of Public Health, the cAIDS Prevention Study Center
(NEPAIDS), University of São Paulo, and the dMunicipal Coordination Office for STD/AIDS Control Policies, Porto Alegre, Brazil.
Correspondence to Ivan França Junior, Av. Dr Arnaldo, 715 sala 218 Faculdade de Saúde Pública, Universidade de São Paulo,
CEP: 01246-904, São Paulo, SP, Brazil.
S59
S60
successive family losses that may lead to institutionalization [2,6]. Institutionalization impacts childhood development and well-being. Institutionalized children receive
less individual attention and love and are consequently ill
prepared for life. They can also suffer increased
discrimination and isolation [1,6].
To date, few studies dealing with children orphaned by
AIDS have been conducted in Brazil, and even less so
with regard to their institutionalization [7–10]. There is
also a scarcity of data on the outcome of AIDS orphans at
a population level. The objective of the present article was
to characterize the children who become orphans as a
result of AIDS and to identify the principal factors
associated with institutionalization.
Methods
Subjects
On the basis of an AIDS mortality surveillance database
and healthcare registries, a cross-sectional study was
conducted by locating the primary caregivers of children
aged 0–14 years who had a parent dying of AIDS in Porto
Alegre during the period 1998–2001.
Children orphaned as a result of AIDS were defined in
conformity with the World Health Organization/
UNAIDS definition [11], which considers orphans to
be all children aged 0–14 years who have lost one or both
parents as a consequence of AIDS. Out of a total of 1654
deaths reported during the period, 38 were excluded
because the individuals were not living in Porto Alegre at
the time of death. When addresses were not available in
the AIDS mortality database, we used other health service
databases (e.g. records from hospital and outpatient
clinics). By these methods, we located 80% of the
addresses of individuals dying of AIDS (83% by AIDS
mortality data, 17% by other health service records). Of
these individuals, 43% had children aged less than 15
years. These 562 individuals had 1131 children, 876
(78%) of these orphaned children were located, and 853
(97%) of these were included in our study (Fig. 1).
Measures
Data were collected by means of a home survey carried
out between June 2002 and February 2003, using a
structured questionnaire. The children’s present caregivers were interviewed in their home or in another place
chosen by the interviewees. The interviews were
conducted by healthcare professionals and undergraduate
students specially trained for the survey who also had
experience working with HIV/AIDS patients.
We chose institutionalization as the primary outcome of
interest. Such children could be living in public or private
orphanages, or also in small family-type units that had
1616 Deaths
(1998--2001)
1294 (80.1%)
Addresses
located
4 (0.3%) Refusals
presence of
children unknown
562 (43.4%)
With children,
eligible
322 (19.9%)
Addresses
not located
728 (56.3%)
No children,
ineligible
1131
Orphans
23 (2.1%)
Refusals
853 (75.4%)
Orphans
located
809 (94.9%)
Orphans not
institutionalized
255 (22.5%)
Orphans not
located
44 (5.1%)
Orphans
institutionalized
Fig. 1. Study population.
guardianship over the orphans by means of a judicial
decision [12,13].
The potential predictors of institutionalization were the
child’s sex, age, skin colour (classified by the caregiver), and
HIV serostatus. Variables related to the parents included age
at the time of death, skin colour, education level, and HIV
serostatus. With regard to the orphaned child’s skin colour,
we collapsed the categories of black and mulatto into ‘nonwhite’ after determining that they had similar statistical
effects. Those of indigenous origin were also added to this
category because of the small number of observations. The
variable of the father’s skin colour was not considered in
the final analysis, because this was unknown for 61% of
the institutionalized children.
Statistical analysis
Differences in proportions were assessed using the chisquared test, with a significance level of 5%. Variables with
P values of 0.20 or less were selected for inclusion in a
multivariate logistic regression analysis. Variables that
were associated with the institutionalization at P < 0.05
or that were shown to be confounders were retained in
the final model. Analysis was performed using STATA
version 7.0 software (StataCorp., College Station, Texas,
USA).
Privacy and confidentiality were observed in accordance
with Resolution 196/96 of the National Health Council
[14]. Written informed consent was obtained from the
subjects interviewed for the research (i.e. the caregivers).
The project was approved by the Research Ethics
Committee of the School of Public Health of the
University of São Paulo.
Children orphaned by AIDS in Porto Alegre, Brazil Doring et al.
Table 1. Characteristics of AIDS orphans and independent factors associated with institutionalization of orphaned children in Porto Alegre,
1998–2001.
Institutionalization
of orphans
Variables
Child with HIV/AIDS
No
Yes
Not knowna
Type of orphanhood
Paternal orphans
Maternal orphans
Double parents
Mother’s skin colour
White
Non-white
Not known
Child’s skin colour
White
Non-white
Total
n
(%)
OR
95% CI
P
550
54
249
25
14
5
5
26
2
1
4.3
0.4
–
1.84; 9.90
0.15; 1.12
–
< 0.01
< 0.08
424
255
174
6
24
14
1
9
8
1
5.9
3.7
–
2.24; 15.50
1.30; 10.57
–
< 0.01
< 0.01
386
447
20
7
26
11
2
6
55
1
4.0
52.3
–
1.32; 12.12
13.25; 214.03
–
< 0.01
< 0.01
369
484
13
31
4
6
1
0.6
–
0.23; 1.59
–
< 0.31
a
All children who had not undergone an anti-HIV test were considered to have an unknown serological situation, independent of the mother’s
serological situation.
Results
A total of 853 orphaned children were included in the
study: 70% had lost their father and 50% had lost their
mother. Out of the total, 21% (175) had lost both parents.
Of the orphans who had lost their fathers, 82% (346) were
living with their mothers, whereas only 20% (52) of those
who had lost their mothers were living with their fathers.
Forty-four children (5%) were institutionalized, 49%
were living with their natural families, 23% were living in
substitute families, i.e. with a defined judicial situation
(guardianship or adoption), and another 23% were living
with family members, friends or neighbours without any
defined judicial situation. Among the institutionalized
children, 73% were living in small family-type units and
27% were still living in large institutions. The median
length of time for which the children had been living in
the institution was 2 years (min. 0.25; max. 15;
interquartile range 1–5.7 years). Of 604 children tested
for HIV antibody (71%), 54 (9%) were positive. Among
those not tested, 207 caretakers (83%) alleged that
mothers were either HIV negative or were infected after
the child or adolescent was born. Eighty per cent of nontested orphans (199/249) had lost their fathers exclusively.
In multivariate analysis, independent predictors of
institutionalization are loss of the mother or both parents,
child HIV positivity and having a mother with a nonwhite skin colour (Table 1). The child’s skin colour was
kept in the final model, even though it was not significant,
because of confounding with mother’s skin colour. There
was mutual adjustment between the variables of losing the
mother, losing both parents, child with HIV/AIDS and
mother’s colour. The final model was well adjusted,
goodness-of-fit test P ¼ 0.10. In addition, the receiver
operating characteristic curve indicated a good predictive
capability of 86%.
On the basis of the adjusted odds ratio, it could be
estimated that being HIV positive multiplied the child’s
chances of living in an institution by a factor of 4.6, loss of
the mother by 5.9, loss of both parents by 3.7, and having
a non-white mother by 4.0.
Discussion
This population-based study provides reliable data on
what has become of the children of AIDS deaths. The
AIDS death register in Porto Alegre has an underreporting of less than 5% [15], and we used other sources
to maximize the number of addresses of cases found when
they were missing in the register.
Overall, few of the AIDS orphans were institutionalized,
and most of them were living in small family units.
Among non-institutionalized orphans, one out of two
was living with a parent, mainly the mother. The greater
proportion of children orphaned by AIDS who lost their
fathers, in comparison with those who lost their mothers,
is probably a result of the fact that men were more affected
at the beginning of the epidemic. Moreover, it is possible
to hypothesize that, given the gender relations in Brazil,
the mother would take on the care of her children. The
future direction of orphanhood as a result of AIDS is
complex because there are many competing factors in the
south of Brazil. The availability of AIDS treatment and
the reduction in the fertility rates of seropositive women
may counterbalance the slight increase in AIDS incidence
and mortality rates in the study area [5,16,17].
S61
S62
In analysing the family situation of the orphaned children
from a legal perspective, it was identified that there were
significant numbers of children living in undefined legal
situations. Despite the abandonment of the policy of child
fostering in Porto Alegre since the 1990s, families are
maintaining the practice of the ‘circulation of children’
even without financial support from the state. This practice
may stave off plenary adoptions recommended by judicial
authorities [18]. The relationship between vulnerability to
violation of rights and legally undefined family situations is
still unknown. Some caregivers have reported difficulties in
dealing with situations of poverty, drug trafficking and
violence experienced in the daily lives of orphaned
children and adolescents in southern Brazil [19].
With regard to the type of institutionalization, the
majority of such children were living in residential
shelters and one-third of them were living in large
institutions. This indicates that Porto Alegre has been
putting into practice what the Statute of the Child and
Adolescent [13] recommended in its articles 92 and 94:
personalized attendance in small groups. This is a better
pathway for facilitating the child’s integration, preferably
within the original family, or within another family. From
this perspective, Marin [20] reported that the proposition
that children should live in small family-type units might
be beneficial, provided that the child is thought of as an
individual with its own history and space, who can go
through self-discovery and find out about others so as to
regain the condition of a citizen and build a new future.
According to ONUSIDA/UNICEF/USAID [2], the
long-term institutionalization of children is detrimental
during infancy, because healthy development from the
emotional point of view requires a constant and loving
caregiver with whom the child can establish bonds and
start the self-identification process. It is very important
that children should receive attention from the family,
either through family members support or adoption.
Sarda [9] stated that newborn children, those aged less
than 18 months, and white-skinned are preferred in
adoption. However, the findings from the present study
did not show any statistically significant difference
between these variables and institutionalization in the
multivariate analysis. On the other hand, non-white skin
colour of the mother was strongly associated with
institutionalization of the child. Colour is a known
marker of inequality for various sociodemographic and
health characteristics [21–23]. Therefore, it is possible
that the children of non-white mothers may have greater
chances of remaining in institutions because they carry
the marks of social and racial inequality.
HIV seropositivity was also a strong determinant of
institutionalization in our study. There are reports that the
children of mothers with HIV/AIDS are only made
available for adoption after they have received a negative
result from anti-HIV testing. As this generally takes place
after the age of 18 months, these children may,
independently of colour, lose the chance of being
adopted. Furthermore, discrimination regarding HIV/
AIDS may be obscuring the preference for colour or age.
Even if children orphaned as a result of AIDS are
seronegative, there may be difficulties in achieving
adoption because they carry the stigma of the disease
from the ignorance and prejudice that are widely present
in society [8]. Stigmatization and discrimination against
children with HIV thus affect their right to family life.
Losing the mother, with or without the concomitant loss
of the father, was the factor of greatest magnitude leading
to institutionalization. As affirmed in several publications
by Fonseca [14,18,24], communities living in situations of
poverty in Porto Alegre have developed strategies for
keeping their children within their communities, even if
parents or close relatives are absent. This results in keeping
children away from action by the judicial authorities for
plenary adoption or institutionalization. Fonseca named
this practice the ‘circulation of children’, which consists
of children rotating between several mothers’ houses (e.g.
from natural mother to godmother, neighbour or
grandmother). An aspect of this child circulation is the
primacy of the rights of the mother (however defined)
over the father’s. The agreements about who keeps the
children are made among the women, and little
importance is given to the genetic fathers’ opinions.
The debate in these communities is between the proverbs
‘there is only one mother’ versus ‘mother is the one who
raises the child’. Therefore, the importance of losing the
mother, but not the father, for increasing the chances of
institutionalization is clear.
We assessed potential biases resulting from the two-stage
missing data: addresses and children. With regard to notfound addresses, there were no significant differences in
terms of age. On the other hand, differential losses were
noted in terms of sex (more men not located) and death
year (losses were smaller for recent years). Stratified
analysis has shown that sex differences were minimized
when adjusted by death year (data not shown), suggesting
that losses of men were related to older AIDS cases. A
possible mechanism for such differential loss may be due
to geographical movement. Data on the mode of
transmission, educational level, and occupational status
were not reliable, because there was missing information
greater than 50%.
At this stage of the survey, we did not know whether the
deceased individual had left an orphaned child/adolescent. One might expect that the over-representation of
women could overestimate the proportion of institutionalized orphans in Porto Alegre.
In terms of losses of children, we found that 2% (23)
refused, 3.1% (35) were living with relatives in other
cities, 6.9% (78) were non-located brothers (few of them
Children orphaned by AIDS in Porto Alegre, Brazil Doring et al.
were living in the streets), and 12.6% (142) were simply
not located. For the latter two categories, we were not
able to collect demographic variables.
Other potential biases are the reliance on memory and
proxy reports from the current caregivers. For example,
we had dubious information regarding the mother’s and
father’s schooling and the father’s skin colour for the
institutionalized children.
Although the Brazilian public health system has been
making antiretroviral treatment available to all individuals
with the indication for several years, access alone has not
been sufficient to stop all deaths from AIDS. The results
from this novel study has provided better knowledge of
the situation for orphans in Porto Alegre, and highlighted
several factors that favour their remaining out of
institutions. Consequently, our findings contribute
towards redirecting actions so that they are more effective
in strengthening the families affected by HIV/AIDS, and
ensuring better living conditions for the children and
adolescents affected and infected by AIDS. In particular,
there is an urgent need for the healthcare and social work
sectors to establish policies that favour an early decision
about who will keep the child after the possible deaths of
those responsible for the child. A discussion of this question with seropositive women is particularly important.
Other policies impacting AIDS orphans include improving the survival of women with AIDS, the early diagnosis
of mothers with HIV, and the incorporation of family
planning counselling into HIV care routine. Of note is
the fact that 90% of women are now tested for HIV
during pregnancy in Porto Alegre, and with treatment,
the transmission of HIV to infants is low. With good HIV
care, early diagnosis and social support, most women
should have the potential to survive through their children’s childhood, postponing a potential orphan crisis, and
decreasing the likelihood of institutionalization.
Acknowledgements
The authors would like to thank the Brazilian Health
Ministry, National STD/AIDS Program, UNESCO, and
Secretaria Municipal de Saúde de Porto Alegre for their
support, and Professor Maria Regina Cardoso, Maria do
Rosário Latorre and Willi McFarland for their reviews.
References
1. UNICEF. The framework for the protection, care and support of
orphans and vulnerable children living in a world with HIV and
AIDS. New York: UNICEF; 2004.
2. UNAIDS; UNICEF; USAID 2004. Children on the brink 2004: a
joint report of new orphan estimates and a framework for action.
Washington, DC: USAID; 2004. Available at: www.unicef.org,
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7. Szwarcwald CL, Andrade CLT, Castilho EA. Estimated number
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8. Núcleo de Estudos e Prevenção para a AIDS. Children and AIDS:
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9. Sarda S. Children and adolescents: rights fulfilment and social
mobilization as a strategy of HIV/AIDS prevention. In: Câmara
C, Carneiro CMP, editors. O outro como um semelhante:
direitos humanose AIDS. Brası́lia: Ministério da Saúde, Secretaria de Polı́ticas de Saúde;1; Coordenação Nacional de DST e
AIDS; 2002.
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poor. Social text 74, vol. 21, no. 1, Spring 2003.
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16. Gray RH, Waver MJ, Serwadda D, sewankambo N, Li C,
Wabwire-Mangen F et al. Population-based study of fertility
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18. Fonseca C. Paths to adoption, 2nd ed. [in Portuguese]. São
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19. Doring M. Final report: Living with HIV/AIDS: a challenge
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da Saúde/Brasil; 2003.
20. Marin ISK. FEBEM, family and identity: the place of the otherness, 2nd ed. São Paulo: Editora Escuta; 1999.
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S63
Sexually transmitted disease/HIV risk behaviour
among women who have sex with women
Valdir Monteiro Pintoa,b, Mariza Vono Tancredib,
Antonio Tancredi Netoc and Cássia Maria Buchallad
Objective: To analyse the epidemiological aspects of sexually transmitted diseases
(STD) among women who have sex with women (WSW) in São Paulo, Brazil.
Method: A cross-sectional study with interviews and analysis of clinical and gynaecological tests in women, by means of a convenience sample. Characteristics were
gathered according to age, sociobehavioural profile, reproductive life and sexuality.
Results: The study included 145 women. They started sexual activity at an average age
of 16.9 years, and 23.4% of them had had heterosexual relations during the preceding
year, with a relatively low frequency of condom use. In sexual relations with women,
54.5% used condoms when they shared sex toys. A previous STD was reported by 38%
of them. The following STD were diagnosed: trichomonas (3.8%), bacterial vaginosis
(33.8%), fungi (25.6%), Chlamydia (1.8%), hepatitis B (7%), hepatitis C (2.1%),
abnormal Pap smear (7.7%), human papillomavirus (6.2%) and HIV (2.9%).
Conclusion: In this study, many WSW did not report a single risk behaviour, but often
reported a combination of several potential risk factors. Therefore, one cannot speak of
high or low-risk behaviour for STD/HIV, but rather of multiple-risk behaviour. It is
evident that there is a need for healthcare professionals to be correctly informed and
sensitive towards the healthcare of WSW.
AIDS 2005, 19 (suppl 4):S64–S69
Keywords: Brazil, epidemiology, HIV, homosexuality, lesbians, sexually
transmitted diseases, women who have sex with women
Introduction
The frequencies of different sexually transmitted diseases
(STD) and risk factors related to gynaecological cancer
among women who have sex with women (WSW) in
Brazil are little known.
Even though several studies have suggested that the risk of
transmitting HIV between women is low [1–3], this
impression may be a result of stereotyping WSW as a
‘group’, and may be the result of the scarcity of studies
that deal with at-risk behaviour among lesbians [4,5].
Several studies have shown that women who have sex
with men and women present a greater risk behaviour of
acquiring STD and HIV than do women who only have
sex with men [5–12]. Other studies have identified STD/
HIV acquired from sexual partners among lesbians
[8,9,13–18].
Not only some health professionals, but also many
lesbians believe that lesbians are not at risk of developing
neoplasia, and thus do not require regular Pap smears.
Nonetheless, findings of abnormal Pap smear tests have
been described among WSW, even among those who
have never had sexual contact with men [14,19].
Moreover, because of the fear of prejudice among
healthcare givers or having gone through previous
unpleasant experiences, some women fail to seek
healthcare services and thus make this population almost
invisible to caregivers [20–27].
From the aNational STD/AIDS program, Brası́lia, the bSTD/AIDS program of the State of São Paulo, the cHeart Institute of
HC-FMUSP, Zerbini Foundation and the dSchool of Public Health of the University of São Paulo, São Paulo, Brazil.
Correspondence to Valdir Monteiro Pinto, MD, Rua Santos Dumont, 136, 04638-000 São Paulo, SP, Brazil.
Tel/fax: +55 11 55393445; tel: +55 11 99807263; e-mail: [email protected]
S64
STD/HIV among women who have sex with women Pinto et al.
The present study had the objectives of ascertaining the
epidemiological characteristics of STD among WSW,
estimating the individual prevalence of each STD,
determining associations between HIV infection and
other STD, and identifying behavioural factors that are
associated with the presence of STD/HIV in this
population.
the sample. EPI-INFO 6.4d (CDC-Centers for Diseases
Control and Prevention, Atlanta, Georgia) and STATA
6.0 (STATA Corp., College Station, Texas, USA) were
utilized for data analysis.
Results
Methods
This was a cross-sectional study in 145 WSW over
18 years old. They were recruited by means of a
convenience sample, from March 2002 to April 2003.
Recruitment publicity was put out on the Internet by
lesbian activist groups, and there was also a leaflet
distribution inviting participation in the study, at the Gay,
Lesbian, Bisexual and Transgender Pride Parade in São
Paulo. Entry into the study was achieved by means of
reading and signing a free and informed consent
statement. Volunteers answered a questionnaire to identify data relating to possible risk factors for STD/HIV:
demographic data and sexual background and practices.
Clinical examination and laboratory tests followed.
During the gynaecological examination, cervical smears
were collected for oncotic cytology, Gram stains, culture
for Neisseria gonorrhoeae, and Chlamydia trachomatis
enzyme-linked immunosorbent assay (ELISA) testing.
Vaginal secretions were examined for fungi with wet
mount, Gram stains and culture. Bacterial vaginosis was
diagnosed using Amsel’s criteria. The Venereal Disease
Research Laboratory and Treponema pallidum haemoagglutination tests were utilized for syphilis. HIV was
diagnosed by ELISA and Western blot tests (Genelabs
diagnostics HIV Blot 2.2, Abbott, St. Ingbert, Germany).
Hepatitis B exposure was assessed using hepatitis B surface
antigen, anti-HBs, anti-HBc and anti-HBe (ELISA using
Elecsys 2010 equipment; Roche). Anti-hepatitis C virus
(ELISA using Core II equipment; Roche, Penzberg,
Germany) was utilized for hepatitis C virus. Genital warts
were diagnosed clinically and via histology.
All volunteers diagnosed with an STD were treated.
This study described and analysed cases of the diagnosis of
one or more STD (excluding Candida and bacterial
vaginosis), in relation to social and demographic
characteristics, risky behaviour of WSW, and factors
associated with the acquisition of HIV. The utilization of
crack cocaine, injection drug use, amphetamines, and
ecstasy were among the behavioural variables surveyed.
Interviewees were asked if they had told physicians they
were WSW, what was the professionals’ reaction and if
there was a change in care. Univariate analysis and odds
ratios calculations were performed, although we did not
obtain statistical significance because of the small size of
Out of the total of 145 women, most were white (64%)
and economically active (85%), and had high levels of
schooling (more than 8 years). Their average age was 31.9
years (standard deviation of 7.90) (Table 1).
The average age of sexual initiation was 16.9 years: 66.2%
of participants reported that their first sexual experience
was with the opposite sex, at an average age of 16.7 years,
whereas 33.8% had had the experience with the same sex,
Table 1. Numbers and percentages of women who have sex with
women, according to sociodemographic characteristics, São Paulo,
2003.
Variables/categories
Age (years)
18–19
20–29
30–39
40–49
50 and over
Colour/race
White
Black
Mulatto
Marital status
Single
Married
Divorced/widowed
Conjugal situation
Single
Living with partner
Employment situation
Active
Inactive
Income (US$/month)a
None
Up to 62.87
> 62.87–251.49
> 251.49–440.11
> 440.11–628.73
> 628.73–817.35
> 817.35–1005.97
> 1005.97
Schooling
Elementary education incomplete
Elementary education completed
High school incomplete
High school completed
College incomplete
College completed
Frequenting of gay, lesbian, bisexual places
Yes
No
Total
Number
%
6
54
58
25
2
4.1
37.2
40.0
17.2
1.4
93
21
31
64.1
14.5
21.4
133
2
10
91.7
1.4
6.9
74
71
51.0
49.0
124
21
85.5
14.5
21
2
56
22
22
9
4
9
14.5
1.4
38.6
15.2
15.2
6.2
2.8
6.2
9
6
13
50
22
45
6.2
4.1
9.0
34.5
15.2
31.0
128
17
145
88.3
11.7
100.0
a
Income was calculated on the basis of Brazilian minimum
salary (R$200.00) and official exchange rate between the Real and
American dollar at each month of the study.
S65
S66
at an average age of 17.4 years. It was found that 23.4%
had never had sexual relations with men.
During the preceding month, 17.9% (26/145) had had
more than one sexual partner, and over the past year, 62%
(90/145) had done so. Sexual relations with men during
the past 3 years were mentioned by 36.6% (53/145) of
volunteers and 32% (17/53) of them said that the men
were either homosexual or bisexual. Condom use in
relations with men, during the past 3 months, was
reported by 45.5% (10/22) of women, and only one
woman reported not having used a condom because she
wished to get pregnant. The consistent use of condoms
was reported by 2.1% (3/143) in relations with women
during the past 3 months. The reasoning for this was that
they ‘didn’t see a need for it’ (42.2%), ‘trusted the partner’
(17.3%) and ‘didn’t know they should’ (16.5%). Previous
histories of STD were reported by 38.6% (56/145).
The exchange of sex for money or goods was reported by
7.6% (11/145) of women. With regard to drug
consumption over the preceding year, from those 112
women who said yes to this question, 40.2% mentioned
marijuana and 16.1% cocaine. No woman reported the
use of injecting drugs. An association between two or
more drugs was frequently mentioned. Sexual relations
with individuals that they knew to be HIV positive were
reported by 12.4% (18/145) of women.
Almost half (44.1%) said that they had sex even when the
partner was menstruating. The use of sex toys was
mentioned by 33.1% (48/145) of them, and of these,
45.8% (22/48) shared accessories and 54.5% (12/22)
changed the condom for shared use.
More than half of the participants were not following a
routine of annual appointments with a gynaecologist.
Attention was drawn to the fact that 3.3% (5/145) had
never visited a gynaecologist; 17.9% (26/145) said they
had never undergone a Pap smear; and more than half of
the interviewees had already had at least one anti-HIV test
(Table 2).
Forty-nine per cent (71/145) said that they had told their
present doctor that they had sexual relations with women,
and 39.3% (57/145) said they had told previous doctors
about this. A feeling of discomfort in the doctor–patient
relationship was the reason given by 91.3% (63/69) of the
women for omitting this information when consulting
with doctors.
Women perceived that their doctor’s reaction towards
being informed of their homosexual practices was to
regard it as ‘natural’, in the case of 43.7% (31/71) of
present doctors and 21.1% (12/57) of previous doctors.
On the other hand, women perceived a ‘negative’
reaction among 21.1% (15/71) of present doctors and
42.1% (24/57) of previous doctors.
Table 2. Numbers and percentages of women, according to their
own healthcare, São Paulo, 2003.
Annual gynaecological appointment
Yes
No
Time of last appointment
Up to 1 year ago
1–3 years ago
More than 3 years ago
Never visited a gynaecologist
Time of last Pap smear
Never had one
Up to 1 year ago
1–3 years ago
More than 3 years ago
Result from the last Pap smear
Never had one
Negative
Class II
CIN I þ HPV
Unable to remember
Anti-HIV test done
Yes
No
Total
Number
%
68
77
46.9
53.1
55
59
26
5
37.9
40.7
17.9
3.3
26
46
51
22
17.9
31.7
35.2
15.2
26
38
32
4
45
17.9
26.2
22.1
2.8
31.0
91
54
145
62.8
37.2
100.0
CIN, Cervical intraepithelial neoplasia; HPV, human papillomavirus.
Among interviewees, 28% (24/85) said that after the
doctors acknowledged their homosexual practices, they
started to attend to them more rapidly or without
looking at them, and 16.5% (14/85) said that the
professional failed to examine them or to request tests
that, according to the women, appeared to be necessary.
Among the laboratory diagnoses, bacterial vaginosis was
demonstrated in 33.8% (48/142) of women. Cultures
for fungi were positive in 25.6% (31/121) of samples.
There was a diagnosis of trichomoniasis in 3.5% (5/142)
of the women and Chlamydia infection was detected in
1.5% (2/134).
Pap smear was shown to be abnormal in 7.7% (11/142)
of women and human papillomavirus (HPV) infection
confirmed by histology was diagnosed in 6.3% (9/142).
Positive serology for hepatitis B and C was found in 7.0%
(10/143) and 2.1%, (3/143), respectively. HIV infection was demonstrated in 2.9% (4/136), and all the
infected patients already knew about their serological
condition (Table 3). It is worth mentioning that only
one woman was diagnosed with HIV and hepatitis C
co-infection.
The four HIV-positive women reported that they had
initiated their sex life at the age of 17 years or less. They
had a history of sexual relations with men at some time in
their lives, had had several partners, and had a history of
STD. Two of them had had less than 8 years of
schooling, three had had sexual contact with men during
the preceding 3 years, and two said they had exchanged
sex for money or goods. Three of them presented with
Table 3. Numbers and percentages of women, according to
observed frequency of sexually transmitted diseases, São Paulo,
2003.
Culture for fungi (n ¼ 121)
Negative
Positive
Trichomonas vaginalis (n ¼ 142)
Positive
Negative
Bacterial vaginosis (n ¼ 142)
Positive
Negative
Chlamydia trachomatis (n ¼ 134)
Reactive
Non-reactive
Pap smear (n ¼ 142)
Negative
Benign cellular alterations
ASCUS
CIN I, II, III
VDRL (n ¼ 143)
Reactive
Non-reactive
HIV (n ¼ 136)
Reactive
Non-reactive
Hepatitis B (n ¼ 143)
Reactive
Non-reactive
Hepatitis C (n ¼ 143)
Reactive
Non-reactive
Indeterminate
Number
and contributes to reducing the stigma felt by these
women, by suggesting changes in the academic education
of health professionals.
%
90
31
74.4
25.6
5
137
3.5
96.5
48
94
33.8
66.2
2
132
1.5
98.5
2
129
4
7
1.4
90.5
2.8
4.9
1
142
0.7
99.3
4
132
2.9
97.1
10
133
7.0
93.0
3
138
2
2.1
96.5
1.4
ASCUS, Atypical Squamous cells of uncertain significance; CIN,
cervical intraepithelial neoplasia; VDRL, Venereal Disease Research
Laboratory.
an abnormal Pap smear. The sample size is too small to
allow for any statistical analysis.
Among women who mentioned the use of sex toys, 31.2%
(15/48) presented with STD, whereas only 14.4% (14/97)
of women not using sex toys had an STD. There was
evidence of an association between STD and the use of sex
toys: odds ratio 2.7 (95% confidence interval 1.15–6.31)
P ¼ 0.01. Other practices such as penetration using hands
and fingers or the manipulation of the partner’s genitalia
in relations in which both were penetrated were reported,
and may present a risk of STD transmission, although the
instrument utilized for data collection did not allow such
an association to be evaluated. No association between
STD and any other risk factor was found.
Discussion
This was the first study in Brazil to approach behavioural
factors in WSW, the diagnosis of STD/HIV and the
relationship of these women with health professionals.
The study helps to expand knowledge on the needs of
WSW, the difficulties they have in obtaining healthcare,
The fact that the study was publicized by means of
the Internet may have induced a selection bias as the
population that has access to it probably has a higher
income and schooling and belongs to socio-economic
strata that are not representative of the general population.
The Gay, Lesbian, Bisexual and Transgender Pride Parade
was the opportunity for publicizing it widely and for
having more representative volunteers of the general
population.
The women in the study had a lower unemployment
rate and higher income than the averages for the
metropolitan region of São Paulo [28]. These characteristics may suggest that the population studied would
have a lower risk of acquiring HIV and other STD,
because of greater access to information, but this was not
observed.
This study reinforces the need for a medical appointment
without value judgements. The fact that 36.6% of the
population studied maintained sexual relations with the
opposite sex during the preceding 3 years indicates that
these women were not exclusively homosexual. The fact
that a woman is a practising homosexual at present does
not indicate that she is exclusively homosexual. The
possible denial of counselling for contraception and
prevention of infection by HIV and other STD, for these
women, is a matter for concern, given that 32% of them
reported that they had had male homosexual or bisexual
partners.
With regard to the use of sex toys, one-third of the
women studied mentioned the practice, and almost half of
them did so in a shared manner, whereas only 54.5%
changed the condom when sharing sex toys. Such
practices could increase the chances of transmitting STD/
HIV because, as well as the exchange of secretions, there
could be contact with the partner’s blood, a risk that was
little perceived by these women.
Among the women studied, 44.1% mentioned that they
had oral sex or penetration (using fingers or sex toys)
while the partner was in the menstrual period. This
percentage was much greater than the 18% found by
Rosário et al. [11], although their study was limited to a
population aged between 14 and 21 years.
Sexual practices in the presence of menstrual blood may
increase the risk of infection, especially by HIV. Some
women justified this risk, showing that they do not
know about or really do not believe in the transmission
risk. The risks of such practices should be publicized more
widely.
S67
S68
Although none of the woman reported the use of
injecting drugs, which, according to Young et al. [29] is an
important risk factor for those women in acquiring
STD/HIV, 74.2% (112/145) were using drugs, including
46.9% (68/145) of tabagism (cigarette smoking), 62.1%
(90/145) of alcohol and 51.7% (75/145) of other
non-injecting drugs. Those characteristics may also be
considered risk-related behaviours.
In addition to these data, there is the information that
12.4% of the women in this study had sexual relations
with male and female partners who they knew to be HIV
positive. This percentage differs from what was found by
Marrazzo et al. [30], whose figures were 4.4% for women
with sexual relations exclusively with women or bisexuals
and 1.2% for women with heterosexual relations, thus
indicating a greater risk among WSW.
Less than half of these women (46.9%) routinely
underwent annual gynaecological evaluation. In addition
to this, 17.9% of women reported that they had never
undergone a cervical cytology examination, which is
similar to the 17% found in the study by Bailey et al. [19]
analysing data from 606 WSW in two sexual clinics for
lesbians in London.
All women with abnormal Pap smear results had had
heterosexual relations at some time in their lives.
Infection by HPV was diagnosed in 6.2% of women,
which was similar to the 8% found by Fethers et al. [31]. In
that study, no difference in the prevalence of abnormal
Pap smear was found between WSW on their first
appointment (n ¼ 1408; average age 27 years) and
women who had never had sex with other women
(n ¼ 1423; average age 26 years). Moreover, two case
reports have described HPV infection among WSW who
had never had sexual relations with men [13,14].
The prevalence of HIV among these women was 2.9%.
This is higher than the rate demonstrated by Fethers
et al. [31] of almost 1%, but similar to the sentinel
study performed by the Centers for Disease Control
and Prevention, cited by Gonzales et al. [10], in which a
2.8% rate was found among 470 HIV-positive bisexual
women.
Almost half of the women in the present study did not
reveal to their doctors that they had sex with other
women. Of this group, almost all of them said that they
omitted the information because they felt some
discomfort caused by the healthcare professional during
the visit. One of the attitudes mentioned was the use of
terms that presupposed heterosexuality, such as ‘your
partner’ (male declination in Portuguese), ‘use of
condoms’, ‘contraception’, thus inhibiting any possible
initiative by the client towards revealing her sexual
orientation.
The majority of interviewees who considered that the
professional’s attitude was ‘natural’ subsequently revealed
that the professional did not provide guidance on the
topic, explaining that the way in which the medical
appointment was conducted merely continued unaltered.
This may result in a lack of specific information regarding
disease prevention.
Attention is drawn to the fact that more than a quarter of
the women reported that the professionals started to
attend to them more rapidly after the revelation of their
sexual orientation, and that the professionals failed to
examine them or to request tests that appeared necessary
to the women. These findings suggest unprepared
professionals, or even stigmatizing among some in
attending to WSW.
Almost all the women interviewed indicated that they
would feel more comfortable during the visit if the
professional ‘were not prejudiced’.
Within this context, healthcare professionals should not
presume that WSW never have sex with men, or that they
are less exposed to the risk of becoming infected by some
STD. They should therefore always stress the importance
of safe sex regardless of sexual practices.
The present study showed that there was rarely any use of
condoms or other protective barrier methods for the
practice of oral sex between women. The reasons
mentioned were that these women did not see any need
for it, did not know they should, or had excessive
confidence in sexual partners.
There is a need for more information for healthcare
professionals and patients regarding the importance of
preventing cervical cancer in WSW. The gynaecological
attendance and routine for WSW should not differ
from what is recommended for heterosexual women,
including guidance and making prevention methods
available.
A large proportion of medical schools do not deal with
the topic of homosexuality and its implications for
healthcare in an integrated manner. For this reason,
healthcare professionals need to review how they conduct
the appointment and how they steer the conversation
regarding the patient’s sex life. They need to leave space in
this dialogue for their clients to feel secure about
admitting their sexual orientation.
The data from this study point towards a need to
introduce and improve measures for preventing and
fighting prejudice, aimed at obtaining better knowledge of the sex life of WSW, providing guidance
regarding risky and vulnerable behaviour, and tracing
out strategies for interventions, monitoring and
evaluations.
Acknowledgements
This study is dedicated to patient R.D., 45 years old, who
as a result of an invasive uterine cervix carcinoma
diagnosed during the study, passed away in March 2003.
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S69
Evaluation of rapid tests for anti-HIV detection
in Brazil
Orlando C. Ferreira Juniora, Cristine Ferreirab, Maristela Riedelc,
Marcya Regina Visinoni Widolinc and Aristides Barbosa-Júniorb
for the HIV Rapid Test Study Group
Objectives: This assessment in Brazil was to evaluate the performance of commercially
available HIV rapid test (RT) against the gold standard testing and to establish a highly
sensitive and specific RT algorithm for HIV diagnosis.
Design: A prospective, anonymous and unlinked study.
Methods: An evaluation of seven commercially available RT to compare their performance against the gold standard tests for Brazil. This includes two competing
enzyme immunoassays plus a Western blot for confirmation. After informed consent,
whole blood samples were collected from volunteers in voluntary counselling and
testing sites (n ¼ 400), antenatal clinics (n ¼ 500) and from HIV-positive controls in
AIDS treatment centres (n ¼ 200). Two seroconversion panels, one HIV-1 subtype
(B, B0 , C and F) panel and an operational assay performance evaluation were also part of
the study parameters.
Results: For the seven RT the clinical sensitivity ranged from 97.74 to 100% and
clinical specificity from 99.43 to 100%. However, only four RT were considered
acceptable after full evaluation. The two EIA had a clinical sensitivity of 100% and
clinical specificity of 99.32 and 99.66%. Two RT had the same performance on
the seroconversions panels as the EIA. The operational assay performance evaluation for the RT indicated that Hexagon and Capillus could not be classified as
simple assays.
Conclusion: We have provided evidence that RT assays can perform equally or better
than EIA for the detection of HIV antibodies. The simplicity and rapidity of the RT
warrants its utilization in an algorithm for a rapid diagnosis of HIV infection.
AIDS 2005, 19 (suppl 4):S70–S75
Keywords: evaluation of rapid tests, HIV rapid test, rapid serological assays,
voluntary and counselling testing and antenatal care, whole blood HIV testing
Introduction
The conventional strategy for the diagnosis of HIV-1
infection in Brazil includes combining two competing
enzyme immunoassay (EIA) screening assays plus a
confirmatory assay, using Western blot or immunofluorescence (referred to as the ‘gold standard’). This
diagnostic system is highly specific and sensitive for the
detection of anti-HIV-1 antibodies but has some operational constraints. It requires highly trained laboratory
From the aLaboratory of Molecular Virology, Department of Genetics, Federal University of Rio de Janeiro, Rio de Janeiro, the
b
Brazilian STD/Aids Programme, Sao Paulo, and the cPublic Health Municipal Laboratory of the city of Curitiba, Curitiba, Brazil.
Correspondence to Orlando C. Ferreira Junior, Laboratory of Molecular Virology, Department of Genetics, Federal University of
Rio de Janeiro, UFRJ, Centro de Ciências da Saúde, CCS, Bloco A, Sala 121, 2nd Floor, Av. Brigadeiro Trompowsky s/n, 21944-970
Ilha do Fundão, Rio de Janeiro, RJ, Brazil.
S70
HIV rapid tests in Brazil Ferreira et al.
technicians and a developed laboratory infrastructure. In
addition, the turnaround time for results to be returned to
the client could be 1–2 weeks or more, thus resulting in
individuals lost to follow-up, delays in diagnosis and
referral to much-needed services.
By 1985, shortly after the introduction of EIA, rapid/
simple anti-HIV-1 tests (RT) became increasingly
available [1]. In the beginning, the performance of
HIV RT assays was poor when compared with EIA.
However, in the past few years rapid/simple assays were
improved and new assays were developed based on new
technologies [2]. As a consequence, some HIV RT assays
have comparable performance with EIA [3–5]. They
require no laboratory expertise and can be executed in a
few steps in less than 20 min.
The World Health Organization recommends a rationalized RT algorithm to diagnose HIV-1 [3]. As the
predictive value of a single screening assay depends on the
HIV prevalence of the population tested, a single HIV RT
assay is not feasible as a tool for a rapid HIV diagnosis.
Therefore, the World Health Organization proposed the
sequential use of two or three different HIV RT assays for
the rapid diagnosis of HIV infection in asymptomatic
individuals. Such a strategy has been applied with success
in other countries [6–8].
In this project we have evaluated seven commercially
available HIV RT assays using whole blood samples from
individuals at voluntary counselling and testing (VCT)
sites and from pregnant women at antenatal clinics
(ANC). Our aim was to create a methodology for the
evaluation of HIV RT assays using whole blood in Brazil.
This effort will pave the way for the development and
future implementation of a three-test algorithm that
would rely only on RT assays for the rapid diagnosis of
HIV infection in Brazil.
Methods
Ethics Committee approval
This was an anonymous unlinked study approved by the
Conselho Nacional de Ética em Pesquisa, CONEP
(Brazilian National Ethic Committee for Human
Research). Informed consent was obtained from each
participant before enrollment.
Sample collection and HIV testing
Between 16 June and 29 August 2003, a total of 1100
samples were collected for the assessment from three
different population sites: (i) from the VCT (n ¼ 400); (ii)
ANC (n ¼ 500); and (iii) from HIV-infected individuals,
as a positive control group (n ¼ 200). After obtaining
informed consent, 5 ml whole blood was collected by
venous puncture in ethylenediamine tetraacetic acid
tubes. Samples were labelled and sent to the Public Health
Laboratory of the city of Curitiba where RT and the
serological gold standard assays were performed on the
same day.
The seven RT evaluated were: Determine HIV-1/2
(Abbott Laboratories, Diagnostics Division, 100 Abbott
Park Road, Abbott Park, II 60064-3500, USA); HIV
Rapid Check (NDI-UFES, Núcleo de Deonças Infecciosas, Universidade Federal do Espirito Santo, Av.
Marechal Campos, 1468 – Maruı́pe, 29.040-091, Vitória
(ES), Brazil); Hexagon HIV 1þ2 (Human GmbH, MaxPlanck-Ring 21, D 65205, Wiesbaden, Germany);
HIV 1/2 STAT PAK (Chembio Diagnostic Systems
Inc., 3661 Horseblock Road, Medford, BY 11763,
USA); Hema-Strip HIV-1/2 (Saliva Diagnostic Systems,
(SDS), 11719 NE 95th Street, Vancouver, WA 98682,
USA); Cappillus HIV-1/HIV-2 and Uni-Gold HIV
(Trinity Biotech plc, IDA Business Park, Bray, Co.,
Wicklow, Ireland). All assays were performed and results
interpreted according to the manufacturer’s packaging
insert recommendations.
Four laboratory technicians rotated in performing two
RT per day, with whole blood in batches of four samples.
Every test result was read by two technicians and by a third
in cases of discordant results.
After completion of the RT, the samples were centrifuged
in order to recover the leftover plasma. The plasma
volume was split into two aliquots: (i) 1–2 ml for the
plasma repository; and (ii) 0.5 ml for gold standard
screening (EIA and, if necessary, confirmatory Western
blot).
Daily, three samples (at least one negative and one
positive) were selected for a quality control procedure. All
seven RT assays were repeated and in case of discordant
results between the initial RT and quality control testing,
a third testing with the initial RT sample batch was
repeated for the assay that scored the discordant result.
The sample final result was the median among the three
results obtained.
In order to ensure comparability, all collected specimens
that underwent RT testing were also evaluated with the
gold standard, including two sandwich EIA from different
manufacturers: Vitrus anti-HIV1/2 (Ortho-Clinical
Diagnostics, Inc., Rochester, New York, USA) and
Axsym HIV-1/2 gO (Abbott GmbH, WiesbadenDelkenheim, Germany) and the New Lav Blot I (BioRad, Marnes-la-Conquette, France) as a confirmatory
assay. Our criteria for Western blot positivity requires the
presence of the p24 gag protein plus any two proteins
from the virus envelope (gp41, gp120 or gp160),
regardless of band intensity.
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In order to address the analytical sensitivity of the assays
used in this study, we have used one commercial
seroconversion panel from Boston Biomedica Inc.
(BBI; panel number PRB931) and an in-house panel
from a seroconverting blood donor, originally identified
by individual nucleic acid technology screening in Brazil.
Assays were also evaluated for performance against an
HIV-1 subtype panel constituted of the main three HIV-1
subtypes circulating in Brazil (B0, C and F) plus the B
subtype. Each subtype was represented by four samples.
Criteria used for acceptance and ranking the
rapid test performance
The criteria used were: (i) clinical sensitivity ( 99.5%);
(ii) sensitivity against the subtype panel; (iii) analytical
sensitivity against the two seroconversion panels; (iv)
clinical specificity ( 99.0%); and (v) operational assay
performance.
The operational assay performance evaluates some
positive (score 1) and negative (score 0) operational
characteristics of the assay as follows: (i) number of
reagents needed to run the assay (1, only one reagent
needed; and 0, more than one reagent needed); (ii)
reagent storage temperature (1, ambient temperature
possible; and 0, 2–88C required); (iii) total number of
assay steps (1, equal to or less than four steps; and 0, more
than four steps); (iv) total performance time (1, equal to or
less than 20 min; and 0, more than 20 min); and (v)
technical skill needed by the operator (1, no laboratory
experience; and 0, laboratory experience recommended).
The assay performance was considered good if the assay
has scored at least four points and poor if less than four
points.
Data management and statistical analysis
Daily results were transferred to an Excel spreadsheet
(Microsoft Windows 2000; Microsoft Corp., Redmond,
Washington, USA) used for data analysis and 95%
confidence interval (CI) calculation.
Results
A total of 1100 samples were screened by seven HIV RT
and the two gold standard EIA. Of the 400 samples from
the VCT site, 23 were repeat reactive on one or both
screening EIA, and of those 18 were Western blot positive
(site prevalence of 4.5%; 95% CI 2.5–6.5%). The other
five samples were Western blot indeterminant (n ¼ 1) or
negative (n ¼ 4). Of the 500 samples screened from the
ANC, six were repeat reactive on one or both EIA and
three samples were Western blot positive (site prevalence
of 0.6%; 95% CI 0.0–1.3%). The other three samples
were Western blot indeterminant (n ¼ 2) or negative
(n ¼ 1). All 200 samples from the positive control group
were repeat reactive on both EIA and Western blot
positive.
Clinical sensitivity and specificity evaluation
By using the gold standard assays, 221 samples were
characterized as Western blot positive and served for the
evaluation of RT clinical sensitivity. All other 879 samples
(from VCT and ANC) were considered HIV-1/2
antibody negative, including the 871 samples negative
on both screening EIA, five samples negative on Western
blot and the three samples with an indeterminant result
on Western blot.
Table 1 demonstrates the clinical sensitivity and specificity
of the RT and the two EIA. All RTexcept the HemaStrip
and Hexagon detected the 221 Western blot-positive
samples (clinical sensitivity of 100%). The Hexagon assay
missed two samples and the HemaStrip assay missed five
samples resulting in a clinical sensitivity of 99.10% (95%
CI 97.85–100%) and 97.74% (95% CI 95.78–99.70%),
respectively.
Table 1. Clinical sensitivity and specificity of the seven rapid tests plus the two gold standard enzyme immunoassays.
Clinical sensitivity (n ¼ 221)
a
Assay
Sens (%)
Determine
RapidCheck
UniGold
Stat Pak
Capillus
HemaStrip
Hexagon
Vitrus EIA
Axsym EIA
100
100
100
100
100
97.74
99.10
100
100
b
Clinical specificity (n ¼ 879)
c
d
95% CI
95% CI
Spec (%)
95% CIb
95% CIc
–
–
–
–
–
95.78
97.85
–
–
–
–
–
–
–
99.70
100
–
–
99.89
99.89
100
99.77
100
100
99.43
99.66
99.32
99.66
99.66
–
99.46
–
–
98.94
99.27
98.77
100
100
–
100
–
–
99.93
100
99.86
EIA, Enzyme immunoassay.
a
Assay clinical sensitivity.
b
Lower bound for the 95% confidence interval (CI).
c
Upper bound for the 95% CI.
d
Assay clinical specificity.
Table 2. Evaluation of the operational assay performance based on five characteristics of the rapid test.
Score for the evaluation of the operational assay performancea
Assay
Determine
RapidCheck
UniGold
Stat Pak
HemaStrip
Capillus
Hexagon
No.
reagents
1
1
1
1
1
0
0
(1)
(1)
(1)
(1)
(1)
(3)
(3)
Reagent storage
temperatureb
1
1
1
1
1
0
0
(2–30)
(2–27)
(2–27)
(8–30)
(2–33)
(2–8)
(2–8)
No.
stepsc
1
1
1
1
1
0
0
(4)
(3)
(3)
(3)
(4)
(6)
(11)
Performance
timed,e
1
1
1
1
1
1
1
(16 : 30)
(10 : 30)
(10 : 30)
(10 : 30)
(15 : 45)
(9 : 00)
(9 : 10)
Technical skills
of operator
Assay performance
1
1
1
1
1
0
0
Good (5/5)
Good (5/5)
Good (5/5)
Good (5/5)
Good (5/5)
Poor (1/5)
Poor (1/5)
a
Values in parenthesis represent actual parameters evaluated.
Temperature range in 8C.
Steps include all activities performed by the operator plus incubation time, before test reading.
d
Performance time includes all incubation time and an average of 15 s per step, except for Capillus (some steps may take 30 s to 1 min) and
Hexagon (average of 20 s per step).
e
Values in parenthesis represents min : s.
b
c
The UniGold, Capillus and HemaStrip assays had a
clinical specificity of 100% followed by the Determine
and RapidCheck assays with a clinical specificity of
99.89% (missed one sample), the Stat Pak assay with a
clinical specificity of 99.77% (missing two samples), and
the Hexagon assay with a clinical specificity of 99.43%
(missing five samples). The Vitrus EIA missed three
samples (two from ANC) and the Axsym EIA missed
six (three from ANC), resulting in clinical specificity of
99.66 and 99.32%, respectively. The nine false-positive
results detected by the RT came from nine different
samples. However, the Hexagon RT and the Axsym
EIA generated false-positive results for the same sample
from ANC. This sample was Western blot indeterminant
with the presence of p24, a weak p55 and a weak
p66 band.
Serconversion panels and HIV-1 subtype panel
All seven RT and the two EIA were tested against two
seroconversion panels. The BBI PRB931 is a nine sample
panel, with the last four samples carrying antibody against
HIV. All RT and EIA but the Capillus RT, gave positive
results for the four samples. Capillus scored positive for
the last three samples only.
Our in-house seroconversion panel is a six-sample panel
with the last four samples carrying antibody against HIV
(samples 3–6). In addition to the two EIA, among the RT
only, the Determine and RapidCheck assays scored a
positive result for the four antibody-positive samples. The
UniGold, Stat Pak and Capillus RT scored positive for the
last three samples only. The HemaStrip RT scored a weak
positive result only for sample number 6. The Hexagon
RT showed an irregular reactivity profile. It was weakly
positive for samples 1 and 4, positive for sample 5 and
negative for sample 6.
All seven RT scored positive results with all 16 samples of
the HIV-1 subtype panel.
Operational assay performance
Five characteristics of the RTwere used for the evaluation
of their operational performance described in the
methods section.
Determine, RapidCheck, UniGold, Stat Pak and HemaStrip had a maximum score (5/5) (Table 2). Typically,
those assays start with the sample application to test device
followed by the addition of a buffer solution, which takes
less than 2 min. Results should be read after 10–15 min,
but for some assays it can be read up to 20 (RapidCheck
and UniGold) or 60 (Determine) min. Any individual
with a specific training on these RT could perform the
assays. Furthermore, the wide temperature range for
reagent storage includes room temperature.
The Capillus assay had a poor performance (scoring 1/5)
(Table 2). It has six steps and utilizes three different
reagents. One of the steps involves the application of latex
beads to the test device and sample mixing, which are
critical to a good assay performance. This step is not
simple, as it requires good laboratory skills. The test result
can be read in approximately 9 min, but it again requires a
well-trained or experienced technician for the recognition of latex agglutination. Illumination of the area
where the test is being performed can also affect
recognition of the agglutination and therefore test
interpretation. Reagents should be kept refrigerated (at
2–88C), limiting test utilization in the field.
The Hexagon assay also had a poor performance (scoring
1/5) (Table 2). It has 11 different steps that can take up 4–
5 min before the final incubation that lasts 5 min and after
which the results should be read immediately. Every step
involves the addition of one out of three different
solutions that should be added timely. It is clear that this
assay requires a great deal of time and attention. Reading
the final result needs good judgement as it involves a
comparison between colorimetric changes developed in
the test area with the one developed in the control area.
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As with the Capillus assay, reagents should be kept
refrigerated (at 2–88C).
Quality control procedure
A total of 157 samples (14.3% of the total 1100) had their
RT repeated for quality control purposes. Two Western
blot-positive samples from the positive control group
showed discordant results when the initial RT was
compared with quality control testing. In one case, the
Hexagon assay was initially negative but quality control
and the third repeat testing were positive, thus correcting
the initial false-negative result.
The second case involved the Stat Pak and HemaStrip
assays. Both assays were positive on initial RT testing but
quality control testing was negative for both assays. The
third repeat testing was weakly positive for the Stat Pak
assay, thus confirming this sample result as positive.
However, the HemaStrip assay again scored a negative.
The clinical sensitivity scorings for these tests were
adjusted accordingly. The Determine, RapidCheck,
UniGold and Capillus RT did not have any discordant
results between initial RT and quality control testing.
Cumulative rapid test evaluation
The RT performance against the subtype panel did not
serve to discriminate performance as all seven RT detected
all four subtypes. Discrimination of assay performance
could be seen on the basis of the other four criteria.
Clinical sensitivity criteria divided the seven RT into two
groups: the Determine, RapidCheck, UniGold, Stat Pak
and Capillus had 100% clinical sensitivity, whereas
Hexagon and HemaStrip assays performed less than the
threshold of 99.5%.
The Analytical Sensitivity ranking is important because it
can help to choose a better assay for screening purposes. Of
note is the fact that the Determine and RapidCheck
assays performed equally well to the two gold standard EIA.
All RT assays met the study criteria for clinical specificity
of 99.0%, three RT assays had a 100% clinical specificity;
six had a clinical specificity above 99.5%. The 100%
clinical specificity observed for the HemaStrip assay may
offset its low sensitivity (97.74%).
The Determine, RapidCheck, UniGold, Stat Pak and
HemaStrip had a maximal operational performance score.
The Hexagon and Capillus assays failed in this criterion as
they scored less than our cut-off value of four points.
Discussion
This study is the first attempt to evaluate systematically
the commercially available RT in Brazil and compare
their performance with the gold standard testing used in
the national algorithm for HIV diagnosis. Five parameters
were considered in the evaluation of seven RT: clinical
sensitivity, clinical specificity, analytical sensitivity, performance against an HIV-1 subtype panel, and the
operational performance of the assay.
All seven RT performed well by these parameters but four
RT were notably better: Determine, UniGold, RapidCheck, and Stat Pak. The data for the clinical sensitivity
and specificity are consistent with the results from other
studies [2,3,7]. However, we should be aware that RT
batch-to-batch variations can affect sensitivity and
specificity.
At least two RT (Determine and RapidCheck) performed equally to EIA when compared against seroconversion panels. Another two RT (UniGold and Stat Pak)
missed only one sample (which would result in a 2-day
difference in the detection of anti-HIV antibodies) from
one seroconversion panel when compared with EIA.
These data provide evidence that the RT is a good
alternative to the use of EIA as a screening test, as has been
suggested by others [3–5,9].
All RTand the two EIA detected all samples of our HIV-1
subtype panel (B, B0, C, F). As the B0, C and F subtypes
are the most important in Brazil [10], we expect that all
seven RT would perform well in the country.
In terms of ease of performance, the Capillus and
Hexagon received lower scores than others RT as they
require more than one reagent that should be kept
between 2 and 88C, involved more than four steps to
complete, and required a laboratory skill level on the
part of the operator. Although they are rapid assays
(performance time is less than 10 min) we found that they
were not easy assays to perform, especially outside a
laboratory environment. The other five RT assays had a
good operational performance with performance time
ranging from 10 : 30 to 16 : 30 (min : s). The characteristics of these five RT make them an excellent option for
rapid HIV diagnosis in situations with limited time,
laboratory conditions and personnel.
Four RT (Determine, RapidCheck, UniGold and Stat
Pak) performed highest according to all evaluation
criteria, and will be used to construct an algorithm for
the rapid diagnosis of HIV infection in Brazil. This RT
diagnostic will subsequently be evaluated to determine its
programmatic value.
Our results show that any pair among the four RTwould
give an accurate test result. On the basis of the analytical
sensitivity, Determine and RapidCheck would have the
same efficacy as the EIA for the purpose of screening. A
discordant result could be correctly resolved by applying a
third, tiebreaker test, overcoming the need for a Western
blot confirmation. In our case, the UniGold would be an
ideal assay for this purpose as it has a clinical specificity of
100%.
The widespread use of two assays for a confirmatory
strategy should be regarded with caution as some pairs of
assays may be susceptible to the same non-specific effects
and thus could generate a false-positive result. We advise
that before implementing this strategy additional evaluations on the specificity of a particular pair of assays should
be performed using a large number of HIV antibodynegative samples.
In conclusion, we have developed a methodology for
the evaluation of RT, and have documented that the
RT can provide highly accurate HIV test results that
equal the EIA in sensitivity and specificity. The advantage
of using an algorithm with RT is its simplicity and rapidity
when compared with the algorithms that utilize EIA
and Western blot for confirmation. These characteristics
can be useful when addressing some high-risk populations in which only one opportunity for counselling
and providing test results is possible. Furthermore, the
adoption of an appropriate strategy could expand the
availability and acceptability of HIV testing and counselling, which may increase the number of individuals
reached for encouraging the adoption of risk-reducing
behaviour.
References
1. Constantine N, Fox TE, Abbatte EA, Woody JN. Diagnostic usefulness of five screening assays for HIV in an east African city
where prevalence of infection is low. AIDS 1989; 3:313–317.
2. Branson BM. Rapid tests for HIV antibody. AIDS Rev 2000;
2:76–83.
3. WHO/UNAIDS. Operational characteristics of commercially
available assays to determine antibodies to HIV-1 and/or HIV2 in human sera. Geneva, Switzerland: World Health Organization/the Joint United Nations Programme on HIV/AIDS, Report
11. WHO/BTS/99.1;UNAIDS/99.5; 1999.
4. Wilkinson D, Wilkinson N, Lombard C, Des M, Alan S, Floyd K,
et al. On-site HIV testing in resource-poor settings: is one rapid
test enough? AIDS 1997; 11:377–381.
5. Ketema F, Zeh C, Edeleman DC, Saville R, Constantine NT.
Assessment of the performance of a rapid, lateral flow assay for
the detection of antibodies to HIV. J Acquir Immune Defic
Syndr 2001; 27:63–70.
6. Kline RL, Dada A, Blattner W, Quinn TC. Diagnosis and
differentiation of HIV-1 and HIV-2 infection by two rapid
assays in Nigeria. J Acquir Immune Defic Syndr 1994; 7:
623–626.
7. Stetler HC, Granade TC, Nuñez CA, Meza R, Terrell S, Amador
L, et al. Field evaluation of rapid HIV serological tests for
screening and confirming HIV-1 infection in Hounduras. AIDS
1997; 11:369–375.
8. Irwin K, Olivo N, Schable CA, Weber JT, Janssen R, Ernst J.
Performance characteristics of a rapid HIV antibody assay in a
hospital with a high prevalence of HIV infection. Ann Intern
Med 1996; 125:471–475.
9. Respess RA, Rayfield MA, Dondero TJ. Laboratory testing
and rapid HIV assays: applications for HIV surveillance
in hard-to-reach populations. AIDS 2001; 15 (Suppl. 3):
S49–S59.
10. Brindeiro RM, Diaz RS, Sabino EC, Morgado MG, Pires IL,
Brigido L, et al. Brazilian Network for HIV Drug Resistance
Surveillance (HIV-BResNet): a survey of chronically infected
individuals. AIDS 2003; 17:1063–1069.
Acknowledgements
This study was partially supported by the Centers for
Disease Control and Prevention, Global AIDS Program,
Atlanta, Georgia, USA and by the Brazilian STD/Aids
Programme, Brasilia, Brazil.
The HIV-1 subtype panel was kindly provided to us by
Dr. Amilcar Tanuri from the Federal University of Rio
de Janeiro. We also want to thank Dr. Mauro Niskier
Sanchez from the Brazilian STD/Aids Programme for his
collaboration in the early phase of this project.
Finally, our thanks to William Brady, Peter Crippen and
Suzanne Westman, from the Centers for Disease Control
and Prevention/Global AIDS Program, for their constant
support and encouragement.
Appendix
Other members of the HIV Rapid Test Study Group are:
Tomoko Sasazawa Ito, Rosamaria Megias Ligmanosvski
Kuss, and Sara Ferraz Vianti from the Public Health
Laboratory of the city of Curitiba; Maria Rita C.B. Almeida
from the VCT; Luiz Carlos Beira, Gefersson Alexandre
Fernandes de Freitas, Danielle Fontoura Teixeira, Márcia
Maria Fantinatti Guerra, Luciana Kusman, Maria Terumi
Kami, Silvana Ribeiro Pienta, Paula Graciela Bochkariov,
Ligia Fatima Simões, Michele Kessler, Patricia Regina
Crozeta, Benedita Almeida dos Santos, Cristiane Ceccon de
Souza Martinelli, Cristiane Yumiko Osawa, Solange
Dalazoana, Tania Mary Medeiros Karvat, Grizeldi Colla,
and Dulce Meri Blitzkow from the Antenatal Clinics.
S75
Estimating the genetic component (RGC) in
pharmacokinetic variability of the antiretroviral
didanosine among healthy Brazilians
Luciane S. Velasquea, Rita de Cassia E. Estrelab,
Guilherme Suarez-Kurtzb and Claudio J. Struchinera
Background: We estimate the variance between between- and within-subjects, using
mixed effect models, as a way to assess the genetic component in explaining the
observed heterogeneity of ddl kinetics among healthy individuals. Our work expands
on a previous reported method known as RGC.
Methods: Repeated measurements of ddl concentration in the serum were obtained
from 48 healthy adult volunteers enrolled in two bioequivalence study. We use the
NONMEM program (Non-linear Mixed Effect Model) to estimate the between- and
within-subject variability and the corresponding pharmacokinetic parameters. We
assess the genetic contribution to the variability of each pharmacokinetic parameter
through the RGC method.
Results: Pharmacokinetic parameters, expressed as functions of covariates gender and
creatinine clearance (CLCR), were: Oral clearance (CL ¼ 55.1 þ 240 CLCR þ 16.6 l/h
for male and CL ¼ 55.1 þ 240 CLCR for female), central volume (V2 ¼ 9.82), intercompartmental clearance (Q ¼ 40.90/h), peripheral volume (V3 ¼ 62.7 þ 22.90 for
male and V3 ¼ 62.70 for female), absorption rate constant (Ka ¼ 1.51 h1) and duration
of the dose administration (D ¼ 0.44 h). The RGC of CL, Q, V3, Ka and D were 0.58,
0.97, 0.60, 0.53 and 0.88, respectively.
Conclusion: We estimated parameter-specific RGC indices and rank them according
to the potential genetic contribution as an explanation for the observed variance.
Our study design improved precision by decreasing background noise and, thus,
improved the chances that indices such as the RGC are in fact describing genetic
variability.
AIDS 2005, 19 (suppl 4):S76–S80
Keywords: genetic component, pharmacokinetic, between-within variability,
didanosine, NONMEM
Introduction
Didanosine is a component of highly active antiretroviral
therapy (HAART) drug combinations, especially in
resource-limited settings and in zidovudine-resistant
patients. AIDS treatment has evolved significantly in
past years as a result of the advent of HAART. This
treatment is based on a combination of antiretroviral
drugs acting at different stages of the HIV replication
cycle. It has been shown that HAART is responsible for a
dramatic reduction in the mortality and morbidity
associated with AIDS [1,2]. HAART is highly efficient
because of the partial reconstitution of the number and
function of CD4 and CD8 T cells by viral suppression.
Nevertheless, HAART is not able to eradicate the virus
and this is partly responsible for therapeutic failure. There
are several factors involved in treatment failure, such as
lack of adherence to therapy, the chosen treatment at the
From the aPrograma de Computação Cientı́fica, Fundação Oswaldo Cruz, and the bCoordenação de Pesquisa, Instituto Nacional de
Câncer, Rio de Janeiro, Brazil.
Correspondence to Luciane S. Velasque, Programa de Computação Cientı́fica, Fundação Oswaldo Cruz. Av. Brasil 436, Rio de
Janeiro, RJ 21045-900, Brazil.
S76
Genetic component in pharmacokinetic variability of didanosine Velasque et al.
beginning of infection, and inadequate knowledge of
medication dosing [3].
Another factor influencing therapy failure is the
variability of the drug response. It is known that for a
given dose of a drug, individual responses can vary
significantly [4,5]. In the presence of full adherence to
treatment, failure is still expected as a result of the
variability in the pharmacological response. This variability is attributable to several possible sources, including
genetic, metabolic and environmental factors [6].
Environmental and physiological factors could inhibit
metabolism, either decreasing or increasing the level of
the drug in the plasma, and may affect the mechanisms
related to the absorption, distribution or excretion of the
drug [4].
In a series of recent articles, Kalow and colleagues [7,8]
and Ozdemir et al. [8] have shown that pharmacokinetic
data collected during the repeated administration of drugs
to healthy volunteers or patients can be used to estimate
the genetic component of drug disposition. They have
proposed a mathematical procedure termed ‘RGC’. This
index helps in assessing the contribution of genetic
sources of between-subject variability to the overall
observed variability of the pharmacological response.
Using this approach, the authors rely on one-way analysis
of variance to estimate the between (SDb2) and within
(SDw2) subject variation and introduce the summary
index RGC ¼ (SDb2 SDw2)/SDb2. Accordingly, RGC
values approaching 1.0 point to an overwhelming genetic
contribution to the overall observed variability, whereas
RGC values close to zero suggest that sources other than
genetic may dominate [8,9].
In the present article, we extended the RGC approach
and estimated between and within-subject variation
through a mixed effect model. The program NONMEM
(non-linear mixed effect model; double precision; version
V; level 1.1) developed by Beal and Sheiner [10]
(NONMEM Project at the University of California)
was used to obtain point estimates and standard deviations
for the pharmacokinetic parameters in a compartmental
model. Our approach allowed us to estimate the RGC
index for each pharmacokinetic parameter.
Methods
Patients
The concentrations of didanosine in serum samples and
the corresponding pharmacokinetic parameter estimates
were obtained from two bioequivalence studies, in which
48 healthy adult volunteers were enrolled and the tested
drug was considered bioequivalent. The study was
conducted in accordance with the revised Declaration
of Helsinki and the rules of Good Clinical Practice. The
clinical protocol was approved by the Ethics Committee
of Instituto Nacional do Câncer, and all participants
provided written and informed consent. Twenty-four (12
male) healthy volunteers were selected for each study
according to medical history, physical examination,
electrocardiogram and standard laboratory test results
(blood cell count, biochemical profile and urinalysis).
The demographic data of these 48 volunteers were: age
19–48 years (median 26), height 145–187 cm (median
166.5), and weight 52–83 kg (median 64.6). The serum
creatinine concentrations, which we used to estimate the
creatinine clearance (CLCR) based on the Cockroft–
Gault equation, ranged from 0.8 to 1.3 (median 1). Each
volunteer was then orally administered 200 mg didanosine oral tablet formulations. Thirteen blood samples
were collected from each volunteer before drug
administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4,
5, 6 and 8 h post-dosing. The concentrations of
didanosine in serum used for the population pharmacokinetics analysis were measured by liquid-chromatography with electrospray ionization tandem mass
spectrometric detection [11].
Pharmacokinetic analysis
Model fitting was done under NONMEM using the
POSTHOC method [12], and the serum didanosine
concentrations were measured after the administration of
the reference formulation (n ¼ 624 samples, 48 subjects).
Our choice of an appropriate statistical model was
preceded by preliminary modelling exercises when we
tried several compartmental models in combination with
different types of additive and proportional withinsubject error structures (results not shown). We finally
settled with the proportional within-subject error
structure and a two-compartment pharmacokinetics
model (ADVAN3 TRANS3) with absorption rate
constant (Ka), clearance (CL), volume of the central
compartment (V2), intercompartmental clearance (Q),
volume of peripheral compartment (V3) and dose
duration (D, used to model the dissolution time of the
tablet: RATE 2). The covariates identified as possible
factors affecting the pharmacokinetic parameters were
formally tested using NONMEM. We retained in the
model the set of covariates that minimized the AIC
statistics [Akaike information criterion 2 log likelihood
þ2(number of parameters)] [13].
We assumed that between-subject variability of the
pharmacokinetic parameters is log-normally distributed;
that is, each parameter value for the ith individual is
expressed as Pi ¼ P̂ þ expðhi Þ, where P̂ is the typical
value of the parameter in the population, and hi is the
between-subject error with mean zero and variance V2.
In addition, within-subject proportional errors were
expressed as Cij ¼ Ĉij(1 þ eij), where Cij is the observed
concentration in serum for the ith individual at time j,
Ĉij is the serum concentration for the ith individual at
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time j predicted by the model, and eij is the residual or
within-subject error with mean zero and variance s2.
Table 1. Didanosine model parameter estimates by NONMEM.
Calculation of modified RGC
As a result of fitting pharmacokinetics mixed effect
population models, we estimate the within-subject
variance (s2) and the between-subject variance associated
with each kinetic parameter (v2 ) of the model. So, it is
P̂
possible to calculate the RGC associated with each
parameter and to know the kinetic stage that contributes
most to genetic variability. The proposed equation is as
follows:
Parameter
Estimate
95% CI
uCL(l/h)
uv2 (l/h)
uQ(l/h)
uv3 (l)
uKa (l/h)
uD(h)
uCLCR CL (l/h)
uSEXV3 (l)
uSEXCL (l/h)
v2CL
v2Q
v2V3
v2Ka
v2D
s2
Objective function
AICa
55.10
9.82
40.90
62.70
1.51
0.44
240.00
22.90
16.6
0.04
0.57
0.04
0.04
0.15
0.02
5081.87
5109.87
22.5–87.7
3.96–15.68
21.08–60.72
50.54–72.46
1.15–1.87
0.40–0.46
10–470
15.76–30.04
5.33–27.26
0.02–0.06
0.07–1.07
0.01–0.06
0.01–0.06
0.09–0.20
0.01–0.02
–
–
RGC CL ¼ 1 s 2 =v2CL
RGC V2 ¼ 1 s 2 =v2V2
RGC Q ¼ 1 s 2 =v2Q
RGC V3 ¼ 1 s 2 =v2V3
RGC Ka ¼ 1 s 2 =v2Ka
RGC D ¼ 1 s 2 =v2D
An RGC value close to 1.0 suggests an important contribution of genetic sources of variability, whereas a value near
zero suggests that variability is affected mostly by environmental sources [7]. Lower and upper bounds of the 95%
confidence intervals were obtained according to Ozdemir
et al. [9] using the statistic F0.25, k–1, k(n–1). Here, k is the
number of subjects (48 subjects) and n is the number of
blood samples collected from the same subject.
Results
Data from a bioequivalence study among healthy
volunteers allowed us to estimate the variability of the
pharmacological parameters in a homogeneous population, that is, without the interference of co-infections
and heterogeneities caused by different stages of disease
progression that could influence the absorption or
distribution of the drug by the patient. Homogeneity
of the study participants was also achieved by controlling
food ingestion and the concomitant use of other drugs
that could interact with didanosine. The homogeneous
conditions under which we estimated RGC for the
various parameters help in the interpretation of these
statistics as an index of the contribution of genetic sources
to overall variability.
Pharmacokinetic compartmental models represent a
tentative description of the drug disposition in vivo. In
this context, each parameter in the model lends itself to a
distinct biological interpretation. This approach allowed
us to identify the pharmacokinetic parameters that
showed the higher variability as a result of the putative
genetic factors, and consequently, which stage of the drug
disposition is most influenced by genetic factors. The
parameter estimates that best fitted didanosine data are
shown in Table 1. Sex had a high and significant (CI did
not include the null value) influence on parameters CL
Final model
AIC, Akaike information criterion; CI, confidence interval; OF, objective function; l/h; litres/h.
a
AIC ¼ OF þ 2 parameter number.
Table 2. Evaluation of the genetic component (RGC) of didanosine
pharmacokinetic parameters through mixed effects model.
Parameter
RGC
95% CI
CL
Q
V3
Ka
D
0.58
0.97
0.60
0.53
0.88
0.25–0.67
0.95–0.98
0.26–0.68
0.24–0.67
0.80–0.91
CI, Confidence interval; CL, oral clearance; D, duration of dose
administration; Ka, absorption rate constant; Q, intercompartmental
clearance; V3, peripheral volume.
and V3. The effect of body weight on the various
parameters was not significant. The within-subject
variability estimate was 0.02 (coefficient of variation
12.96%). The RGC calculated for all parameters are
shown in Table 2.
Discussion
The decomposition of total variance into between and
within-subject components constitutes the main rationale
for studies on the identification of genetic determinants.
This decomposition is achieved via one-way analysis of
variance statistical models and the ratio of the two
components yields the RGC index [7,9]. Data on repeated
measurements on the same individual allow the direct
estimation of within-subject variance. Between-subject
variance is obtained as the difference between total
variance and within-subject variance. Data from studies
on twins or with repeated drug administration have been
used in the medical literature for estimating these
variances. In the statistical literature, another way to
Several diagnostic procedures indicate that the final
model estimated by NONMEM fitted the data well, as
shown in Figs 1 and 2. The within-subject (residual)
variability was estimated to be approximately 13% (CV),
which indicates that most of the total variability in the
data was explained by the model.
2500
0
500
1000
1500
2000
Predicted didanosine concentration (ng/ml)
Fig. 2. Scatter plot of weighted residual versus didanosine
concentration predicted by the final model developed in the
present study.
individual variability is higher in that phase of didanosine
kinetics. High RGC values are also associated with the
dissolution time of the tablet (D). This parameter was
highly significant in the model, and added considerably to
improve the model fit. Its importance in describing the
absorption of didanosine has also been reported in Faulds
and Brogden [14]. This behaviour was attributed to
mechanisms associated with variations in gastric degradation, gastrointestinal motility and transit time, and the
metabolism by intestinal bacteria [14]. Our study is based
on data on healthy individuals, to whom the same
mechanisms apply, and we also observed extensive
variability in the absorption phase of didanosine. Studies
that assess data on these other dimensions, so they can be
controlled for, are necessary to provide evidence on
genetic contributions as a better explanation of the
putative mechanism associated with the observed
between-subject variability.
500
1000
1500
2000
Sponsorship: G.S-K. and C.J.S. were supported by
research grants from CNPq, Fundação Ary Frauzino
(FAF) and Fundação de Amparo à Pesquisa do
Estado do Rio de Janeiro (FAPERJ). L.S.V. and R.E.E.
were supported by graduate scholarships from
FAPERJ and the Instituto Nacional de Câncer,
respectively.
References
0
Predicted didanosine concentration (ng/ml)
The intercompartmental clearance (Q) was associated
with the highest estimated RGC. This shows that
Weighted residuals
0
2
We use the NONMEM program to fit a compartmental
model to pharmacokinetics data and thus estimate the
between-subject variability of each parameter. These
parameters roughly describe or approximate physiological
mechanisms, implying that knowledge about the
parameter-specific genetic contribution also indicates
knowledge about the stage-specific genetic contribution
to drug disposition. These models also account for
additional covariates, such as sex and CLCR, to explain
the total variance. Parameter estimates are interpreted as
controlled for the explanatory variables when these
variables are present in the compartmental model. This is
a very popular strategy to achieve homogeneity. The use
of data collected from healthy volunteers enrolled in a
bioequivalence study can be seen as an additional strategy
to improve precision. These data allow for smaller total
variability because factors such as food ingestion, the use
of concomitant drugs and some additional external factors
have been controlled for by design. In conclusion, all
study choices described above add up to improve
precision by decreasing background noise, and thus
improve the chances that indices such as the RGC are
describing genetic variability.
−2
estimate within and between-subject variance uses mixed
effect models or hierarchical models. The models
proposed by us in this work belong to this latter class.
4
Genetic component in pharmacokinetic variability of didanosine Velasque et al.
0
500
1000
1500
2000
Observed didanosine concentration (ng/ml)
2500
Fig. 1. Scatter plot showing the relationship between the
serum didanosine concentrations measured in 48 healthy
volunteers treated with 200 mg of the reference didanosine
formulation (abscissa) and the corresponding concentrations
predicted by the final model developed in the present study
(ordinate). The continuous line is the identity line.
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less. N Engl J Med 1997; 337:725–733.
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4. Lu AYH. Drug-metabolism research challenges in the new
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6. Kalow W. Pharmacogenetics in perspective. Drug Metab
Dispos 2001; 29:468–470.
7. Kalow W, Ozdemir V, Tang BK, Tothfalusi L, Endrenyi L. The
science of pharmacological variability: an essay. Clin Pharmacol Therapeut 1999; 66:445–447.
8. Kalow W, Endrenyi L, Tang BK. Repeat administration of drugs
as a means to assess the genetic component in pharmacological
variability. Pharmacology 1999; 58:281–284.
9. Ozdemir V, Kalowa W, Tang BK, Paterson AD, Walker SE,
Endrenyi L, et al. Evaluation of the genetic component of
variability in CYP3A4 activity: a repeated drug administration
method. Pharmacogenetics 2000; 10:373–388.
10. Beal S, Sheiner L. The Nonmem system. Am Statistician 1980;
34:118–119.
11. Estrela RDE, Salvadori MC, Raices RSL, Suarez-Kurtz G.
Determination of didanosine in human serum by on-line
solid-phase extraction coupled to high-performance liquid
chromatography with electrospray ionization tandem mass
spectrometric detection: application to a bioequivalence
study. J Mass Spectrom 2003; 38:378–385.
12. Sheiner L, Beal S. NONMEM user’s guide. San Francisco, CA:
University of California at San Francisco; 1994.
13. Akaike H. New look at statistical-model identification. IEEE
Trans Auto Control 1974; AC19:716–723.
14. Faulds D, Brogden RN. Didanosine – a review of its antiviral
activity, pharmacokinetic properties and therapeutic potential
in human-immunodeficiency-virus infection. Drugs 1992;
44:94–116.
HIV-1 subtype C dissemination in southern Brazil
Esmeralda A.J.M. Soaresa, Ana M.B. Martı́nezb, Thatiana M. Souzaa,
André F.A. Santosa, Vanusa Da Horab, Jussara Silveirab, Francisco I.
Bastosc, Amilcar Tanuria and Marcelo A. Soaresa
Objectives: To describe the molecular and epidemiological profile of HIV-1 in patients
followed at the University Hospital of Rio Grande, Brazil.
Design and methods: A cross-sectional study was conducted from September to
December 2002. Plasma viral RNA of 85 patients was extracted and protease and
reverse transcriptase genes were polymerase chain reaction-amplified and sequenced.
Sequences were subtyped and examined to antiretroviral resistance mutations. Laboratory data and past history of antiretroviral treatment were also collected.
Results: Most viruses were either subtype B (42%) or subtype C (45%). No risk
behaviour, sexual orientation or laboratory parameter was associated with any specific
subtype, but subtype C tended to be more frequently found in women (P ¼ 0.06). The
prevalence of subtype C has increased over the HIV/AIDS epidemic, accounting for
almost 60% of cases diagnosed in 2002. Intra-subtype genetic distances were smaller in
subtype C than in subtype B, suggesting a more recent introduction of the former in the
epidemic. Of patients under treatment, 60% had at least one antiretroviral drug
resistance mutation, but no mutation was specifically associated with any HIV-1
subtype. Only one resistance mutation each was found in drug-naive patients with
subtypes B and C.
Conclusion: Despite the fact that subtype C appeared in southern Brazil more recently
than subtype B, it is now the predominant strain in Rio Grande. The epidemic spread of
subtype C could be taking place in Brazil, and possibly in south America, a phenomenon similar to that seen in other countries where this subtype is now totally dominant.
AIDS 2005, 19 (suppl 4):S81–S86
Keywords: HIV-1, molecular epidemiology, southern Brazil, subtype C
Introduction
HIV-1 of subtype C is currently the most prevalent virus
subtype and it is found in more than 56% of HIV
infections worldwide [1]. Subtype B prevails in the
developed countries of western Europe and the United
States where HIV infections are concentrated in high-risk
populations such as men who have sex with men and
injection drug users [2]. Subtype C is more prevalent in
countries with high HIV infection rates among
heterosexuals, such as those of sub-Saharan Africa [3–
8] and the populous countries of India and China [9–12].
It is believed that subtype C has risen above other
previously prevalent subtypes in these regions [13,14]. In
Brazil, although subtype B is still more common
nationwide, subtype C has been increasingly prevalent
in the southern region [15,16]. Although regional studies
have suggested an increase in subtype C, such studies were
carried out in state capitals and did not assess the inland
spread of the HIV epidemic characteristic of Brazil [17].
The city of Rio Grande is located in the outermost
southern Brazil, near the Uruguayan and Argentine
borders. The economy of Rio Grande is based on port
activity and ships from Africa and Asia arrive at its local
harbours. A study carried out in this city revealed a 22%
From the aLaboratório de Virologia Molecular, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, the bDepartamento de
Patologia, Fundação Universidade Federal do Rio Grande, RS and the cInstituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
Correspondence to Marcelo A. Soares, Laboratório de Virologia Molecular, Universidade Federal do Rio de Janeiro, CCS-BL.ARM.A2-121, Cidade Universitária, Ilhado Fundás, 21949-570, Rio de Janeiro, RJ, Brazil.
S81
S82
point prevalence of subtype C in 1997 [18]; however, less
is known about the temporal trends in the prevalence of
subtype C, its geographical distribution and the potential
contribution of Brazil to the spread of subtype C virus in
South America.
The present study aims to describe the molecular and
epidemiological profile of HIV-1 in the city of Rio
Grande, in the state of Rio Grande do Sul. The
distribution dynamics of virus subtypes at different times
throughout the HIV/AIDS epidemic is described as well
as the spread of their genetic diversities in the study
population. Finally, the universal availability of antiretroviral drugs in Brazil also made it possible to examine
the genotypic resistance of subtype C to treatment, a
phenomenon rarely studied elsewhere in the world.
Materials and methods
Study population and sample collection
A consecutive sample of 100 HIV-positive patients
routinely seen at the HIV/AIDS outpatient clinic of the
University Hospital of Rio Grande participated in the
study from September to December 2002. Upon
informed consent (provided by 100% of those invited),
a plasma specimen was collected and existing medical
records were reviewed. The University Hospital is the
only public health centre providing care to HIV-positive
patients in Rio Grande and the surrounding cities and it is
a reference centre in the southern part of the state of Rio
Grande do Sul. Currently, approximately 1200 patients
are now followed in that centre. Study inclusion criteria
included age more than 18 years, available past and
current medical records, laboratory tests (viral load and
CD4 T-cell counts) and date of HIV diagnosis. Patients
diagnosed between 1988 and 2002 were included. For
each patient, a standardized data abstraction form
recorded the date of diagnosis, the last 15 CD4 T-cell
counts and HIV viral load estimations, clinical information and past and current antiretroviral treatment
regimens and their duration was compiled.
Plasma was separated at the Federal University of Rio
Grande (FURG) Laboratory of Molecular Biology, and
approximately 1 ml was sent packed in dry ice to the
Federal University of Rio de Janeiro (UFRJ) Laboratory
of Molecular Virology for subsequent processing. At
UFRJ, plasma was stocked at 708C until further
processing.
Viral RNA extraction, polymerase
chain-reactions and sequencing
As previously described [19], viral RNA was extracted
from plasma and complementary DNA synthesis was
immediately carried out with random primers. Polymerase chain reactions (PCR) were conducted in two
steps with specific nested primers. The entire gene of the
protease region (PR) and the first 225 codons of reverse
transcriptase (RT) were amplified, purified using the
Qiagen kit (Qiagen, Valencia, California, USA) and
sequenced in an automated ABI 3100 sequencer (Applied
Biosystems, Foster City, California, USA). Sequencing
chromatograms were aligned in PC/Windows using
SeqMan software (DNAStar, Madison, Wisconsin, USA)
and manually edited.
Of 100 samples processed for PCR and sequencing,
molecular information on one of the genomic regions
(PR or RT) was obtained from 85 cases. Thirty-six (42%)
had both regions analysed, whereas 23 (27%) had only PR
and 26 (31%) had only RT available for analysis. Most of
the remaining 15 samples (11/15; 73%) were from
subjects under treatment with undetectable plasma viral
loads (< 80 copies of viral RNA per millilitre of plasma)
and thus were not able to be included in the analysis.
Phylogenetic and drug resistance
mutation analyses
The corresponding sequences to PR and RT genes were
aligned to reference sequences representative of all HIV-1
subtypes obtained from the Los Alamos database (http://
hiv-web.lanl.gov) in ClustalW [20]. Aligned sequences
were subjected to phylogenetic inference through the
neighbour-joining method and Kimura 2-parameter
model of the MEGA 2.1 package [21] for the inference
of HIV-1 subtypes. Mean genetic distances of subtype C
and B samples were determined using the Li93 method
[22] of the MEGA 2.1 package [21]. The genotypic
interpretation of antiretroviral drug-resistant mutations in
the PR and RT genes was carried out through electronic
submission to the Stanford database (http://hivdb.stanford.edu) [23]. Mutations were gathered according to the
International AIDS Society–USA consensus statement
[24]. Gene sequences obtained in the study were
submitted to the GenBank database and were assigned
the access numbers DQ190951 – DQ191039.
Statistical analyses
Continuous variables (age, time from diagnosis, CD4
T-cell counts and log10 HIV viral loads) were compared
between subtype B and C groups using Student’s t-tests.
Categorical variables [sex, exposure categories, Centers
for Disease Control and Prevention (CDC) clinical and
immunological stages and treatment status] were compared using the chi-squared test with Yates’ correction.
Temporal trends of subtype prevalence over the epidemics
were evaluated by chi-squared for trend.
Results
Epidemiological features
Table 1 shows the demographic characteristics, risk
category, laboratory and molecular markers and treatment
status of the 85 patients with virus molecular information.
HIV-1 subtype C dissemination in southern Brazil Soares et al.
Table 1. HIV subtypes by demographic, clinical, and laboratory characteristics among patients of University Hospital of Rio Grande, Rio
Grande, Brazil, 2002.
Mean age (years) SD
Sex (%)
Male
Female
Mean diagnosis time (years) SD
Exposure categories
Homo/bisexual
Heterosexual
Injection drug user
Haemophiliac/transfusion
Unknown
CDC clinical stage (%)
A
B
C
Non-identified
CDC immunological stage (%)
1
2
3
Mean CD4 T-cell count (SD)
Treated
Non-treated
Median log10 of viral RNA
Treated log
Non-treated log
Treatment status (%)
Treated
Non-treated
Interrupted treatment
Total (n ¼ 85)
Subtype B (n ¼ 36)
Subtype C (n ¼ 38)
35.2 11.0
37.3 11.5
32.9 10.1
45 (53%)
40 (47%)
3.4 3.1
24 (67%)
12 (33%)
3.6 3.0
16 (42%)
22 (58%)
2.8 2.5
15
50
15
2
3
(18%)
(59%)
(18%)
(2%)
(3%)
8 (22%)
19 (52%)
5 (14%)
2 (6%)
2 (6%)
5 (13%)
27 (71%)
6 (16%)
0
0
29 (37%)
17 (22%)
32 (41%)
7
12 (36%)
6 (18%)
15 (45%)
3
16 (47%)
8 (24%)
10 (29%)
4
14 (16%)
43 (51%)
28 (33%)
5 (14%)
20 (56%)
11(31%)
8 (21%)
19 (50%)
11 (29%)
246 (157)
395 (260)
254 (167)
520 (426)
265 (167)
375 (195)
3.7
3.9
3.5
3.6
4.0
3.9
48 (56%)
25 (29%)
12 (14%)
25 (69%)
6 (17%)
5 (14%)
15 (40%)
19 (50%)
4 (10%)
CDC, Centers for Disease Control and Prevention. All statistical comparisons were not significant unless otherwise stated in the text.
The mean age was 35 years, men-to-women ratio was
1 : 1, and the mean estimated length of HIV diagnosis was
3.4 years. Of all patients, 41% were in clinical stage C and
33% in immunological stage 3 according to CDC criteria
at the time of sample collection. Fifty-six per cent of patients were under antiretroviral drug treatment, whereas
the remainder did not meet the Brazilian criteria for
receiving drug treatment (www.aids.gov.br/final/biblioteca/adulto_2004/consenso.doc) and thus were treatment-naive or had received treatment in the past but
were not under treatment at the time of sample collection.
HIV-1 subtype profile
Phylogenetic analysis of viral PR and RT determined that
45% of the samples were subtype C, 42% were subtype B,
5% were subtype F1, 2% were subtype D, and 6% were
recombinant samples (three F1/B, one D/B, and one
B/C). Of note is the fact that the B/C recombinant
found was from a recently diagnosed individual. Subtypes
C and B comprised almost 90% of studied samples, and
demographic and laboratory data from these samples were
compared separately (Table 1, columns 3 and 4). The
mean age, mean length of diagnosis, exposure category,
clinical stage, CD4 T-cell counts, viral load and treatment
status were similar in the groups of patients infected with
subtypes B and C, and no statistically significant
differences were found. However, a marginal significance
was seen in the sex proportion for both subtypes; subtype
C was more frequently seen in women (P ¼ 0.03, nonadjusted chi-squared test; P ¼ 0.06 after Yates’ correction). An apparent difference was observed between
patients classified according to CDC clinical staging,
although such a difference did not reach statistical
significance. Forty-five per cent of the subtype B group
were stage C, whereas 47% of the subtype C group were
stage A (Table 1). With regard to treatment, 69% of the
subtype B group had already undergone previous
treatment or were currently under treatment compared
with 40% of the subtype C group (P ¼ 0.02, chi-squared
test after Yates’ correction).
Dynamics of HIV-1 subtypes throughout
HIV/AIDS epidemic
Despite being equally represented in the sample overall,
there was a tendency towards an increasing proportion of
subtype C over subtype B over time. Figure 1 shows an
increasing relative proportion of subtype C from 36% of
cases before 1997 to 58% of cases in 2002. However,
this trend was not statistically significant (P ¼ 0.18, chisquared test for trend).
S83
significant (P < 0.001, Student’s t-test) whereas the
difference in RT means was borderline (P ¼ 0.07).
Fig. 1. HIV-1 subtype proportions according to diagnosis
period, Rio Grande, Brazil, 1988–2002. B; C; F1; D;
mosaic.
In order to corroborate the hypothesis of a more recent
introduction of subtype C in the region, mean genetic
distances in PR and RT sequence groups were compared
between subtypes B and C. The mean sequence distance
in PR of the subtype C group was 4.2% (SE 0.5%) at
nucleotide level compared with 7.3% (SE 0.8%) in the
subtype B group (Fig. 2a). As for RT, subtype C
sequences showed a mean distance of 5.9% (SE 0.5%)
compared with 6.2% (SE 0.5%) seen in subtype B (Fig.
2b). The mean distance differences in PR were highly
35
30
No. of sequences
Profile of genotypic resistance to
antiretroviral drugs
The availability of antiretroviral drug treatment in Brazil
since 1987 and the highly active antiretroviral therapy
with PR inhibitors since 1996 has made the southern
region an attractive area for studying the subtype C virus
response to treatment. Among patients currently under
any antiretroviral drug treatment (n ¼ 48), 57% had at
least one resistance mutation to RT nucleoside analogues.
Of those receiving RT non-nucleoside inhibitors as part
of their current regimens, 54% had at least one mutation
for these drugs. Of those receiving protease inhibitors (PI,
n ¼ 33), 38% had at least one primary PI mutation. We
found no specific association between HIV-1 subtypes
and specific resistance mutations (data not shown). Of the
treatment-naive patients (n ¼ 25), only one subtype B
sample had a PI L90M mutation and one subtype C
sample had a V82I mutation.
Discussion
Our study shows a high prevalence of HIV-1 subtype C in
Rio Grande, a port city that borders other south
American countries. The temporal trend analysis of
HIV subtype distribution among diagnosed cases
throughout the epidemics showed that subtype C has
prevailed over subtype B, which used to be more
prevalent.
(a)
25
20
15
10
5
0
0.01
0.04
0.06
0.08
0.11
0.13
0.15
Genetic distance
(b)
25
No. of sequences
S84
20
15
10
5
0
0.02
0.03
0.05
0.07
0.08
0.1
0.11
0.13
Genetic distance
Fig. 2. Interpatient pairwise genetic distances between protease and reverse transcriptase sequences of subtypes B and
C, Rio Grande, Brazil, 1988–2002. (a) Protease sequences of
subtypes B ( ) and C ( ). (b) Reverse transcriptase sequences
of subtypes B ( ) and C ( ).
Several lines of evidence in our study point towards an
increase in subtype C in southern Brazil. An increasing
proportion of subtype C over time in the epidemics, the
younger age of subtype C-infected individuals, the
shorter time of diagnosis for those subjects, less advanced
clinical and immunological stages in the subtype C
group, a smaller proportion of subtype C-infected
subjects under treatment and genetic variation in the
pol gene all argue in favour of a more recent introduction and expansion of this subtype. Although some of
this evidence is not statistically significant or is of
borderline significance, taken together they support such
a hypothesis.
The recent predominance of subtype C over other
subtypes has been described in many countries [4–12],
and has also recently been described by our group in the
city of Porto Alegre, the state capital of Rio Grande do
Sul [14]. However, we now report an even higher
prevalence in the city of Rio Grande. Furthermore, a
separate study in the city of Rio Grande among HIVinfected women in labour found the percentage of
subtype C to be greater than 70% [25]. These findings
HIV-1 subtype C dissemination in southern Brazil Soares et al.
support the hypothesis that subtype C has actually
prevailed over subtype B outside the capital cities of
southern Brazil, and in fact may have been introduced
into the country through Rio Grande. Of note is the fact
that Rio Grande is one of the largest seaports in Brazil and
serves as the southernmost transportation hub to
neighbouring countries. Although earlier studies in
Uruguay, Argentina, Paraguay, and Bolivia have not
detected cases of subtype C infection [26–28], a more
recent study has documented subtype C strains in these
countries [29]. Besides spreading from south to north as
earlier proposed [15,30], it is possible that subtype C is
similarly spreading down throughout South Cone
countries, reaching neighbouring nations towards the
outermost south. Further investigation in these bordering
regions is needed to evaluate the local impact of Brazilian
subtype C in other south American HIV/AIDS
epidemics.
The present study also showed that subtype C was
introduced in Rio Grande later in the HIV/AIDS
epidemic than subtype B. This has been evidenced by the
lower mean genetic diversity found in both the PR and
RT genes seen in subtype C when compared with
subtype B. The same assumption was discussed in an
earlier study in southern Brazil [31], and the present study
data further corroborates such a hypothesis.
The finding that subtype C was more frequent among
women merits consideration. It may reflect the introduction of subtype C coinciding temporally with the
increasing feminization of the HIV epidemic in Brazil
[17]. It may also reflect a relatively higher rate of the male
to female transmission of subtype C compared with
subtype B. The differential efficiency of infection among
distinct subtypes, in particular with respect to the
infection of Langerhans cells, has been suggested in
earlier studies [32,33].
Our data do not answer the question as to why subtype C
is able to prevail over other subtypes. It has been proposed
that subtype C is actually less fit than subtype B in vitro
[34], but these findings have not been corroborated
in vivo. In the present study, even although the mean
diagnosis times were not significantly different in
both subtypes B and C, it took longer for patients
infected with subtype C to start antiretroviral drug
therapy and this was probably postponed because of a
slower clinical progression according to CDC criteria. It
is possible that this longer asymptomatic phase seen in
subtype C-infected patients makes its epidemic dissemination more efficient than that of subtype B, and could
explain the epidemiological predominance of subtype C.
However, HIV sexual transmission during the asymptomatic phase is eight to 10 times less likely than in acute
infections [35], and this might not be epidemiologically
relevant.
With regard to resistance mutations to antiretroviral
drugs, no resistant isolates to all three classes of
antiretroviral drugs among treated subjects were
observed, a finding similar to other studies in Brazil
[16,36]. The fact that there were almost no treatmentnaive patients infected with resistance mutation viruses
corroborates recent low estimates of primary (transmitted) resistance in Brazil [37], and even in the state of
Rio Grande do Sul [16].
In addition to the small sample size that provides low
power to many comparisons, we recognize other
limitations of our study. The use of subjects with
HIV/AIDS in care raises the question of how representative our sample is to the larger epidemic. Nonetheless, the care unit sampled follows a large proportion of
all cases in Rio Grande. Another limitation is determining
the patients’ timing of infection. In the present study, we
are forced to rely on imperfect markers for the timing of
infection, including the date of diagnosis, stage of disease,
immunological stage, and age. New assays to detect recent
infection, such as the BED capture enzyme immunoassay
[38], may help with the interpretation of data from newly
diagnosed patients.
Despite limitations, our data provide useful public health
information. HIV heterosexual prevention policies
should be stressed in southern Brazilian states, where
higher rates of subtype C can be found and are now
prevailing over the other variants. It is worth highlighting
the fact that the southern region is the only one in the
country where the HIV/AIDS epidemic has been
increasing [39], and the association of this growth and
subtype C virus should be further investigated. A rapid,
stronger response to the HIV/AIDS epidemic in
southern Brazil should be taken to prevent the emergence
of another focus for the epidemic spread of this subtype,
as seen in several countries of sub-Saharan Africa and
south-east Asia.
Acknowledgements
The authors are deeply indebted to University Hospital
FURG HIV/AIDS Unit staff for their help with data
collection and the clinical follow-up of patients. They
would also like to thank Professor Rodrigo Brindeiro
(UFRJ) for his support to this study and Mônica Arruda
and Adriana Afonso (UFRJ) for their technical support.
The study was part of the PhD thesis of E.A.J.M.S.,
granted by the Coordination of Scientific Improvement
in Universities.
Sponsorship: This study was funded by the Brazilian
Ministry of Health STD/AIDS Program and Research
Support Foundations of the state of Rio de Janeiro and
Rio Grande do Sul.
S85
S86
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