Guidelines

Guidelines
Hans-Jürgen Stellbrink, Hamburg
Disclosures
• Scientific Secretary of the German AIDS Society,
responsible for guideline development
• Member of the EACS guideline committee
• Member of the National AIDS Advisory Board
• Consultant and speaker for
- Abbott (AbbVie), Bristol-Myers Squibb, Merck,
Sharp & Dohme, Janssen Cilag, ViiV Healthcare,
Gilead Sciences
• Investigator in clinical trials for
• Merck, Sharp & Dohme, Janssen Cilag, ViiV
Healthcare, GSK, Pfizer, Gilead Sciences
2
DAIG HIV Guidelines / Recommendations
• Antiretroviral therapy in adults (Dec 2015)
• Treatment and prophylaxis of opportunistic infections
(Sep 2014)
• Assessment of HIV-1 coreceptor usage (May 2014)
• HIV treatment during pregnancy and in HIV-exposed
newborns (May 2014)
• Anal dysplasia and anal carcinoma (Jun 2013)
• Postexposure prophylaxis (Jun 2013)
• Antiretroviral therapy in children and adolescents
(Mar 2013)
• Therapeutic drug monitoring (Feb 2012)
• HIV-2 guidelines (work in progress)
3
There are many HIV treatment guidelines
Guideline
EACS guidelines 20151
GeSIDA/Plan Nacional 20162
French HIV expert group 20143
British HIV association 20154
DHSS 20155
IAS-USA 20146
Italian HIV guidelines
working group7
Russian guidelines 20148
DAIG/ÖAG guidelines 20159
WHO guidelines 201510
Expert panel demographics
mainly Western/central European
Spain
France
UK
USA
US (+1 author from India +1 from Brazil)
Italy
Russian
Austria and Germany
USA and Africa
1. EACS guidelines version 8.0. Available at: http://www.eacsociety.org/guidelines/eacs-guidelines/eacs-guidelines.html; 2. Spanish HIV guidelines 2016
Available at: http://www.gesida-seimc.org/contenidos/guiasclinicas/2016/gesida-guiasclinicas-2016-tar.pdf; 3. Hoen B et al. J Int AIDS Soc. 2014; 17: 19034; 4.
BHIVA guidelines 2015. Available at: http://www.bhiva.org/HIV-1-treatment-guidelines.aspx; 5. DHHS Guidelines, 2015. Available at:
https://aidsinfo.nih.gov/guidelines; 6. Günthard H et al. JAMA. 2014;312:410–25; 7. Antinori A et al. New Microbiol. 2015;38:299–32; 8. Russian guidelines.
Available at: http://www.hivrussia.org/files/Protokol_corr.pdf; 9. German/Austrian guidelines 2015 revision, in press; Stellbrink personal communication; 10.
WHO guidelines. Available at: http://www.who.int/entity/hiv/pub/guidelines/earlyrelease-arv/en/index.html
German-Austrian ART Guidelines 2015
Short Summary
The full version of the German-Austrian
ART Guidelines 2015 is accessible under:
http://www.daignet.de/site-content/hivtherapie/leitlinien-1
German-Austrian ART Guidelines 2015
Recommendations for treatment initiation were graded as follows:
Grading
Explanation
To be initiated
Treatment is clearly indicated
Should be initiated
Treatment is indicated, but deferral is justifiable
May be initiated
Treatment is an option
Should not be initiated
Treatment is not indicated
Recommendations regarding choice of drugs were graded as follows:
Grading
Explanation
Recommended
Preferred drug / combination
Alternative
May be given, may be the best choice for some
patients
Not recommended
Only for special cases, but remains an option
Not indicated
Is not an option
German-Austrian ART Guidelines 2015
Start of treatment
CD4+
T cell count
ART
Any value
To be initiated
< 500/µl
To be initiated
> 500/µl
Should be initiated
Acute retroviral syndrome with
prolonged / severe symptoms
Any value
To be initiated
Asymptomatic/ mild symptoms
during seroconversion
Any value
Should be initiated
Symptoms
HIV-associated symptoms and
diseases (CDC: C, B), HIVAN1,
HAND2, and pregnancy3
Asymptomatic patients
(CDC: A)
1. HIVAN: HIV-associated nephropathy; 2. HAND: HIV-associated neurocognitive disorder, 2. See separate Guidelines
for antiretroviral treatment during pregnancy (http://www.daignet.de/site-content/hiv-therapie/leitlinien-1)
When to start: Major guidelines for ART initiation in 2016
Guideline
AIDS or
HIV-related
symptoms
CD4+ cell count (cells/mm3)
<200
200–350
350–500
>500
EACS guidelines 20151
Highly
recommended
Highly
recommended
Highly
recommended
Recommended
Recommended
German/Austrian DAIG/ÖAG 20152
Highly
recommended
Highly
recommended
Highly
recommended
Highly recommended
Recommended
GeSIDA/Plan Nacional 20163
Highly
recommended
Highly
recommended
Highly
recommended
Highly recommended
Highly
recommended
French HIV expert group 20144
Highly
recommended
Highly
recommended
Highly
recommended
Highly recommended
Highly
recommended
British HIV association 20155
Highly
recommended
Highly
recommended
Highly
recommended
Highly recommended
Highly
recommended
DHSS 20156
Highly
recommended
Highly
recommended
Highly
recommended
Highly recommended
Highly
recommended
IAS-USA 20147
Highly
recommended
Highly
recommended
Highly
recommended
Highly recommended
Highly
recommended
Italian HIV guidelines working group8
Highly
recommended
Highly
recommended
Highly
recommended
Highly recommended
Recommended
Russian guidelines 20149
Highly
recommended
Highly
recommended
Highly
recommended
Highly recommended
Recommended
WHO guidelines 201510
Highly
recommended
Highly
recommended
Highly
recommended
Highly recommended
Highly
recommended
1. EACS guidelines version 8.1. Available at: http://www.eacsociety.org/guidelines/eacs-guidelines/eacs-guidelines.html. 2. German/Austrian guidelines 2015 revision, in press; Stellbrink personal communication
3. Spanish HIV guidelines 2016 Available at: http://www.gesida-seimc.org/contenidos/guiasclinicas/2016/gesida-guiasclinicas-2016-tar.pdf; 4. Hoen B et al. J Int AIDS Soc. 2014; 17: 19034
5. BHIVA guidelines 2015. Available at: http://www.bhiva.org/HIV-1-treatment-guidelines.aspx; 6. DHHS Guidelines, 2015. Available at: https://aidsinfo.nih.gov/guidelines; 7. Günthard H et al. JAMA. 2014;312:410–25
8. Antinori A et al. New Microbiol. 2015;38:299–32; 9. Russian guidelines. Available at: http://www.hivrussia.org/files/Protokol_corr.pdf
10. WHO guidelines. Available at: http://www.who.int/entity/hiv/pub/guidelines/earlyrelease-arv/en/index.html
START study: Is there a potential for waiting ?
INSIGHT START Study Group. N Engl J Med. 2015;[Epub ahead of print]. Lundgren J, et al. IAS 2015. Abstract MOSY0302.
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German-Austrian ART Guidelines 2015
Combination Partner 1
Nucleoside-/ Nucleotide
combinations
Recommended:
Tenofovir1/Emtricitabine (FTC)
Abacavir2/Lamivudine
Alternative:
Tenofovir/Lamivudine
Combination Partner 2
+
Integrase inhibitors
Recommended: Dolutegravir
Raltegravir
Elvitegravir/c*(+TAF/FTC
)
Alternative:
(+TDF/FTC)
Elvitegravir/c
NNRTI
Recommended : Rilpivirine3
Alternative:
Efavirenz4
Proteaseinhibitoren
Recommended : Atazanavir/r#
Darunavir/r
Alternative:
Lopinavir/r
1. Tenofovir either given as Tenofovir-Disoproxilfumarat (TDF) or Tenofoviralafenamid (TAF), 2. Only for HLA-B*5701-negatives; Cave: possibly
elevated cardiovascular risk, virologically slightly inferior, 3. Cave: not if HIV-RNA >100,000 copies/mL (not licensed), 4. not during first trimester
of pregnancy */c: Cobicistat, #/r: Ritonavir
What to start: Major guidelines for ART initiation in 2016
Guideline
EACS (Oct
2015)1
DAIG/ÖAG 20152
Initial options
INSTIs: DTG + TDF/FTC; DTG +
ABC/3TC , RAL + TDF/FTC;
EVG/c/TDF/FTC
Boosted PIs: DRV/r +
TDF/FTC
NNRTIs: RPV + TDF/FTC
Tenofovir/FTC or ABC/3TC plus one of the following options: DTG
or RGV or RPV or DRV/r or ATVr OR TAF/FTC/EVG/c.
Alternatives are (NRTI) TDF + 3TC, (3rd drug) EFV or LPV/r or TDF/FTC/EVG/c
GeSIDA/Plan
Nacional 20163
INSTIs: DTG + TDF/FTC; DTG + ABC/3TC; RAL + TDF/FTC;
EVG/c/TDF/FTC
French HIV
expert group 20144
TDF/FTC plus one of the following
four options: EFV; RPV; ATV/r;
DRV/r
BHIVA 20155
TDF/FTC plus one of the following six options:
ATV/r; DRV/r; DTG; EVG/c; RAL; RPV
DHSS
20156
ABC/3TC plus one of the
following two options: EFV; ATV/r
INSTIs: DTG/ABC/3TC; DTG + TDF/FTC;
EVG/c/TAF/FTC; EVG/c/TDF/FTC; RAL +
TDF/FTC
Boosted PI:
DRV/r + TDF/FTC
1. EACS guidelines version 8.0. Available at: http://www.eacsociety.org/guidelines/eacs-guidelines/eacs-guidelines.html. 2. German/Austrian guidelines 2015 revision, in press; Stellbrink personal communication
3. Spanish HIV guidelines 2016 Available at: http://www.gesida-seimc.org/contenidos/guiasclinicas/2016/gesida-guiasclinicas-2016-tar.pdf; 4. Hoen B et al. J Int AIDS Soc. 2014; 17: 19034
5. BHIVA guidelines 2015. Available at: http://www.bhiva.org/HIV-1-treatment-guidelines.aspx; 6. DHHS Guidelines, 2015. Available at: https://aidsinfo.nih.gov/guidelines
What to start: Major guidelines for ART initiation in 2016
Guideline
IAS-USA 20141
Initial options
INSTIs: DTG + TDF/FTC; DTG +
ABC/3TC, RAL + TDF/FTC;
EVG/c/TDF/FTC
NNRTIs: EFV + TDF/FTC; EFV +
ABC/3TC; RPV + TDF/FTC
Boosted PIs: ATV/r + TDF/FTC;
ATV/r + ABC/3TC; DRV/r +
TDF/FTC
Italian HIV guidelines
working group2
INSTIs: DTG + TDF/FTC; DTG +
NNRTIs: EFV + TDF/FTC; EFV +
ABC/3TC; RAL + TDF/FTC;
RAL + ABC/3TC ;
ABC/3TC; RPV + TDF/FTC
EVG/c/TDF/FTC
Boosted PIs: ATV/r + TDF/FTC;
ATV/r + ABC/3TC; DRV/r +
TDF/FTC; DRV/r + ABC/3TC
Russian guidelines
20143
NNRTI:
EFV
WHO guidelines 20134
NNRTI: EFV + TDF/FTC; EFV + TDF/3TC
+
2 NRTIs: AZT-F; ABC; TDF; ZDV; 3TC;
TDF/FTC
1. Günthard H et al. JAMA. 2014;312:410–25; 2. Antinori A et al. New Microbiol. 2015;38:299–32
3. Russian guidelines. Available at: http://www.hivrussia.org/files/Protokol_corr.pdf; 4. WHO guidelines. Available at:
http://www.who.int/hiv/pub/guidelines/arv2013/art/artadults/en/
Indikation zur HIV-PEP bei nicht-beruflichen HIVExpositionen (Teil1)
Parenterale Exposition
Expositionsereignis
PEP-Indikation
Versehentliche Transfusion von HIV-haltigen Blutkonserven oder
Erhalt von mit hoher Wahrscheinlichkeit HIV-haltigen Blutprodukten
oder Organen
PEP empfehlen
Nutzung eines HIV-kontaminierten Injektionsbestecks durch
mehrere Drogengebrauchende gemeinsam
PEP empfehlen
Verletzung an altem, weggeworfenem Spritzenbesteck – z.B. bei
spielenden Kindern
Keine PEP-Indikation
Sexuelle Exposition
Expositionsereignis
PEP-Indikation
Ungeschützter insertiver oder rezeptiver vaginaler oder analer
Geschlechtsverkehr (z.B. infolge eines geplatzten Kondoms) mit
einer bekannt HIV-infizierten Person
PEP empfehlen
-wenn Indexperson
unbehandelt bzw. VL > 1000
Kopien/ml
- wenn Behandlungsstatus nicht
eruierbar,
PEP anbieten
wenn VL der Indexperson 501000 Kopien/ml
Keine PEP-Indikation
wenn Indexperson wirksam
behandelt (VL< 50 Kopien/ml)
Deutsch-Österreichische Leitlinie zur Postexpositionellen Prophylaxe der HIV-Infektion; Stand 2013
Indikation zur HIV-PEP bei nicht-beruflichen HIVExpositionen (Teil2)
Sexuelle Exposition bei unbekanntem HIV-Status der Indexperson
Ungeschützter Analverkehr zwischen Männern
PEP anbieten
Wenn ungeschützter Analverkehr wiederholt
erfolgt (Anamnese!) sollte zusätzlich eine
Präventionsberatung empfohlen werden
Ungeschützter heterosexueller Vaginal- oder
Analverkehr
… mit aktiv intravenös Drogen konsumierendem
Partner/in
… mit bisexuellem Partner
… mit Partner/in aus HIV-Hochprävalenzregion (v.a.
Subsahara-Afrika)
… bei Vergewaltigung
PEP anbieten
Ungeschützter heterosexueller Vaginal- oder
Analverkehr (auch mit Sexarbeiterin)
Keine PEP-Indikation
Oralverkehr
Keine PEP-Indikation
Keine Einigkeit bezüglich PEP-Indikation
ungeschützter oraler Geschlechtsverkehr mit der
Aufnahme von Sperma eines sicher oder
wahrscheinlich HIV-infizierten Partners in den Mund
Küssen
Keine PEP-Indikation
Kontakt von HIV mit Haut
Deutsch-Österreichische Leitlinie zur Postexpositionellen Prophylaxe der HIV-Infektion; Stand 2013
Standardprophylaxe
Standardprophylaxe: Isentress 1 Tablette zweimal täglich plus Truvada 1 Tablette einmal
täglich über 28-30 Tage
Standard
Raltegravir + Tenofovir-DF/Emtricitabin = Isentress® + Truvada®
Dosierung:
Isentress 400 mg 1 - 0 - 1
+Truvada 245/200 mg 1 - 0 - 0
Alternativen
Alternativ zu Isentress® (Raltegravir) kann Kaletra® (Lopinavir/ Ritonavir),
alternativ zu Truvada® (Tenofovir-DF/Emtricitabin) kann
Combivir® (Zidovudin/Lamivudin) eingesetzt werden.
Dosierungen: Kaletra 200/50 mg 2 – 0 – 2
Combivir 300/150 mg 1 – 0 - 1
US guidelines: TDF/FTC + RAL1
Die Standard-PEP bei einer Schwangeren besteht aus
WHO guidelines: TDF + XTC + LPV/r or ATV/r²
Lopinavir/rit + Tenofovir-DF/Emtricitabin
EACS guidelines: TDF/FTC + RAL or DRV/r or LPV/r or DTG³
Truvada
245/200mg
+ Kaletra, 2x 400/100mg.
1.=Kuhar
DT et al.1x
(2013)
http://www.jstor.org/stable/10.1086/672271
2.http://apps.who.int/iris/bitstream/10665/145719/1/9789241508193_eng.pdf?ua=1
3. http://www.eacsociety.org/files/2015_eacsguidelines_8_0-english_rev-20160124.pdf
Deutsch-Österreichische Leitlinie zur Postexpositionellen Prophylaxe der HIV-Infektion; Stand 2013
Algorithmus zur Prävention, Diagnostik und Therapie
von Condylomata acuminata, analen intraepithelialen Dys/Neoplasien und Analkarzinomen bei HIV-Infizierten
HPV
negativ
Vorgeschichte
ggf.
HPVTypisierung
Routineuntersuchung
einmal pro Jahr
für alle HIV-Infizierten
Inspektion,
Palpation
Anamnese,
Abstrich,
Zytologie
S. Esser
LR HPV
nein
AIN
high risk Patient,
HR HPV
nein
Normal
ja
Normal
ja
siehe Legende*
ja
ja;
nein
(HR)
Anoskopie
kurzfristig,
spätestens
innerhalb
von 3 Monaten
(Essigsäure,
Lugol`sche Lsg)
nein; kurzfristig spätestens
innerhalb von 3 Monaten
Suspekter
Befund
nein
bei Erstvorstellung
und alle drei Jahre
persistiert
> 12 Monate
LSIL/
ASCH/ASCUS
HSIL
innerhalb von 3-6 Monaten
Suspekter
Befund
ja
PE
nein
Suspekte
Zytologie
nein;
ggf. ungezielte PE`s
aus Anoderm
ja
ja
ja:
Wiederholung
Abstrich,
Zytologie
innerhalb
von
3-6 Monaten
nein
nein
Normal
ja; innerhalb von 3-6 Monaten
Analkarzinom
Carcinoma in situ,
AIN II, AIN III
Condylomata
acuminata,
AIN I
Wiederholung
Abstrich,
Zytologie
kurzfristig spätestens innerhalb von 3 Monaten
Staging
Legende*:
nein
Lokaltherapie
und/oder
operative
Entfernung
ggf.
therapeutische
Vakkzinierung
Radiochemotherapie
kurzfristig spätestens innerhalb von 3 Monaten
operative
Entfernung in
Einzelfällen bei
Analrandkarzinom
möglich
Wiederholung
Inspektion, Palpation,
Abstrich, Zytologie,
Anoskopie ggf. PE
ohne
Behandlung
innerhalb
von
3-6 Monaten
Patient startet
Algorithmus
erneut
Normal
ja;
2x normale Zytologie
ja
4x nein; innerhalb von 12 Monaten
Suspekter
Befund
3x nein; innerhalb von 12 Monaten
2x nein; innerhalb von 3-6 Monaten
nein; innerhalb von 3-6 Monaten
Wiederholung
Inspektion, Palpation,
Abstrich, Zytologie,
Anoskopie ggf. PE
AIN
high risk Patient,
siehe Legende*
Aktuell oder
Vorgeschichte:
- Condylomata
acuminata
- HPV-assoziierte
intraepitheliale
Neoplasien (IN)
unabhängig von ihrer
Lokalisation
(oral, genital, anal)
- Analkarzinom
Guideline development
Guideline recommendations may be based on
• Evidence
• Eminence
• Eloquence
17
Evidence-based
E
V guidelines
Consensus-based
guidelines
Confounding
factor
Guidelines are not commandments, but a
road map to success
Alternative recommended
• Guidelines define minimum and maximum standards and provide a
„treatment avenue“. Deviations should be justified.
• National Guidelines adapt recommendations to national financial and
logistic constraints, as well as drug availability.
• Ambitious treatment recommendations in international guidelines may
exert pressure on national politics and may aid drug availability.
18
The quality of care continuum
too little
acceptable
adequate
superb
Guideline framework
The specialist‘s tendency
Third party payer‘s tendency
19
too much
Thank you very much
for your attention !
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