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Antiretroviral drugs for HIV post-exposure
prophylaxis (PEP): Update
Kenneth Mayer
Professor of Medicine Harvard Medical School
Medical Research Director, The Fenway
2014
Simplification and standardization towards a public
health approach
Focus on risk rather than exposure type: single guideline for all
Preferred recommendations for adults, adolescents and children
- Alignment with recommendations for ART
Emphasis on simplification to support completion rates:
- Full course prescription (28 day)
- adherence support
Proportion completing PEP by population
Covariate
AIDS 2014: Abstract TUPE154
Proportion
completing PEP
Studies
Patients
Eligibility for PEP: Best Practice Guidance
1.
2.
3.
PEP should be offered, and initiated as early as possible to all persons
with a HIV exposure, and ideally within a window of 72 hours
Assessing the eligibility for PEP should be based on the HIV status of the
source whenever possible and may include consideration of background
prevalence and local epidemiological patterns*
Exposures that may warrant PEP include:
1.
2.
4.
Exclusions for PEP would include:
1.
2.
5.
Bodily fluids (semen, cervicovaginal secretions, blood)
Mucous membrane
Index patient positive from another source
Source is HIV negative
In some settings with high background HIV prevalence all eligible
exposures may be considered for PEP without a risk assessment
* Reference the Swiss Statement and CDC guidelines
Backbone drug
Third drug
Adults & adolescents
Preferred
TDF+XTC
+
LPV/r or ATV/r
Alternative
TDF+XTC*
+
RAL/r or DRV/r or EFV*
Preferred
AZT+3TC
+
LPV/r
Alternative
TDF+XTC
ABC+3TC
+
ATV, RAL, NVP (<3
years) and EFV* or DRV
(>3 years)
Children (≤ 10 years)
* AZT + 3TC in case of intolerance/contraindication to TDF+XTC
*concerns about CNS side effects
Supporting evidence: adults & adolescents
Backbone TDF+XTC • ART: 3 RCTs show fewer discontinuations due to AEs for TDF vs
drugs
AZT (RR 0.6)
• PrEP: 4 RCTs found no difference in risk of SAEs comparing
TDF+XTC vs placebo (RR 1.0)
• PEP: 15 observational studies found lower rates of discontinuations
due to AEs with TDF+XTC (0.3%) compared to AZT (3.2%), and
higher rates of PEP completion (78% vs 59%)
3rd drug
LPV/r
ATV/r
• Limited, low quality data to inform 3rd drug choice. Preference based
on cost, availability, and experience with use in PEP
• Some data support good tolerability for RAL and DRV/r in PEP but
cost/availability a limitation for resource-limited settings
• Data from ART shows good tolerabilty (<5% discontinuations in first
3 months) but limited data for PEP
• Poor acceptability among health providers and assaulted people
• Insufficient data about newer integrase inhibitors
Supporting evidence: children
Backbone
drugs
AZT+3TC • PEP: Some published data for use in PEP (<5% discontinuation due to AE)
Third drug
LPV/r
• ART: 1 RCT in naive HIV-infected children found no difference in adverse
events comparing AZT+3TC and ABC+3TC
• Other considerations: Availability of age-appropriate formulations and
alignment with adopted 1st line ART in countries, side-effect profile in the
context of short-term exposure in HIV-negative population
• PEP: No data is available on the use of 3rd drug for PEP
• ART: 3 RCTs in HIV-infected naive children less than 3 years found no
difference in grade 3 and 4 AEs between LPV/r and NVP-based ART.
Similarly, 1 RCT conducted in older children did not found a difference in
AEs between PI and NNRTI use.
• Other considerations: LPV/r is currently the preferred choice for 1st
(<3 years) and 2nd-line ART and drug is widely available and affordable
compared to newest drugs such as DRV, ATV and RAL that are not
available in age-appropriate formulations. Harmonization across
populations and age-groups within childhood is of value.
Starter packs vs full prescriptions
Outcomes
Partial course
Full course
Among those eligible at presentation
Refused PEP
22.4%
(16.7-28.1%)
11.4%
(5.3-17.5%)
53.2%
(44.4-62.2%)
70.0%
(56.7-77.3%)
0.3%
(0.1-0.6%)
0.6% (0.1-1.1%)
8.2% (6.3-10.1%)
11.2% (5.3-17.0%)
6.8%
(5.1-8.4%)
4.2% (1.6-6.8%)
28.0%
(21.4- 34.5%)
0
Among those initiating PEP
Completed PEP
Stopped: exposed HIV+ve
Stopped: source HIV-ve
Stopped because of adverse drug reaction
Defaulted on incomplete course
AIDS 2014: Abstract TUPE155
Enhanced adherence support
Control better
Intervention better
NPEP Research Priorities
Access
• Understanding barriers to accessing PEP for all population groups
Drug choice • Research to inform future drug choices for adults, adolescents and children
– Toxicity monitoring
– Drug-drug comparisons
– Resistance profiling / regimen selection
• Drug – drug interactions
• The potential use of newer antiretrovirals ( DTG, RIL, EVG/cobi) for PEP.
Adherence
Follow up
• Optimal adherence interventions – effectiveness, resource considerations, cost
effectiveness
• Impact of pill burden on adherence to PEP
• Optimal testing strategies at follow up
• Strategies and impact of transitioning from PEP to PrEP
Next steps
Draft
guidelines
GDG review
Final Recs text
JULY
External peer
review
Submit to
GRC
EARLY AUG
END AUGUST
Presentation on
expected direction of
PEP guidance
Finalisation
and
publication
OCT
Acknowledgements
Guideline Development Group
Chair: Kenneth Mayer (The Fenway Institute, USA)
GRADE methodologist: Nandi Siegfried (Independent Consultant, South Africa)
Linda Barlow (John Hopkins University and Makerere University, Uganda), Ferenc Bagyinszky (European AIDS
Treatment Group, Belgium), Alexandra Calmy (Geneva University Hospital, Switzerland), Mohamed Chakroun
(Fattouma Bourguiba Teaching Hospital, Tunisia), Esther C Casas (Medecins Sans Frontieres, The Netherlands),
Kenneth Dominguez (Centres for Disease Control and Prevention, USA), Kimberley Green (Family Health
International, Ghana), Christiane Rapparini (Universidade Federal de Rio de Janeiro, Brazil) Htin Aung Saw
(Specialist Hospital Mingalardone, Myanmar), Francois Venter (WITS Reproductive Health and HIV institute,
South Africa), Zhao Yan (The National Centre for AIDS/STD Prevention and Control, China Center for Disease
Control and Prevention, China).
UN partners
Sathyanarayanan Doraiswarmy (The UN Refugee Agency (UNHCR), Switzerland), Lee-Nah Hsu (International
Labour Organization (ILO), Switzerland), Atieno Ojoo (The United Nations Children’s Fund (UNICEF) Denmark),
Wilma Doedens (The United Nations Population Fund (UNFPA)).
WHO
Coordination: Nathan Ford (HIV), Rachel Beanland (WHO consultant, HIV), and Cadi Irvine (WHO consultant,
HIV).
WHO steering group: Rachel Baggaley (HIV), Meg Doherty (HIV), Claudia Garcia Moreno Esteva (Reproductive
Health and Research), Jane Ferguson (Maternal, Newborn, Child, Adolescent Health), Gottfried Hirnschall
(Director, HIV), Martina Penazzato (HIV), Francoise Renaud (HIV), Marco Vitoria (HIV).