Presentation on theme: "Antiretroviral drugs for HIV post-exposure prophylaxis (PEP): Update"— Presentation transcript:
1 Antiretroviral drugs for HIV post-exposure prophylaxis (PEP): Update Kenneth MayerProfessor of Medicine Harvard Medical SchoolMedical Research Director, The Fenway2014
2 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: - starter packs - adherence support Simplification and standardization towards a public health approachFocus 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
3 Proportion completing PEP by population Covariate Proportion Studies Patientscompleting PEPAIDS 2014: Abstract TUPE154
4 Eligibility for PEP: Best Practice Guidance PEP should be offered, and initiated as early as possible to all persons with a HIV exposure, and ideally within a window of 72 hoursAssessing 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:Bodily fluids (semen, cervicovaginal secretions, blood)Mucous membraneExclusions for PEP would include:Index patient positive from another sourceSource is HIV negativeIn 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
5 ATV, RAL, NVP (<3 years) and EFV* or DRV (>3 years) Backbone drugThird drugAdults & adolescentsPreferredTDF+XTC+LPV/r or ATV/rAlternativeTDF+XTC*RAL/r or DRV/r or EFV*Children (≤ 10 years)AZT+3TCLPV/rTDF+XTC ABC+3TCATV, RAL, NVP (<3 years) and EFV* or DRV (>3 years)* AZT + 3TC in case of intolerance/contraindication to TDF+XTC *concerns about CNS side effects
7 Supporting evidence: adults & adolescents Backbone drugsTDF+XTCART: 3 RCTs show fewer discontinuations due to AEs for TDF vs 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 drugLPV/rATV/rLimited, low quality data to inform 3rd drug choice. Preference based on cost, availability, and experience with use in PEPSome data support good tolerability for RAL and DRV/r in PEP but cost/availability a limitation for resource-limited settingsData from ART shows good tolerabilty (<5% discontinuations in first 3 months) but limited data for PEPPoor acceptability among health providers and assaulted peopleInsufficient data about newer integrase inhibitors
8 Supporting evidence: children Backbone drugsAZT+3TCPEP: Some published data for use in PEP (<5% discontinuation due to AE)ART: 1 RCT in naive HIV-infected children found no difference in adverse events comparing AZT+3TC and ABC+3TCOther 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 populationThird drugLPV/rPEP: No data is available on the use of 3rd drug for PEPART: 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.
9 Starter packs vs full prescriptions OutcomesPartial courseFull courseAmong those eligible at presentationRefused PEP22.4%( %)11.4%( %)Among those initiating PEPCompleted PEP53.2%( %)70.0%( %)Stopped: exposed HIV+ve0.3%( %)0.6% ( %)Stopped: source HIV-ve8.2% ( %)11.2% ( %)Stopped because of adverse drug reaction6.8%( %)4.2% ( %)Defaulted on incomplete course28.0%( %)AIDS 2014: Abstract TUPE155
10 Enhanced adherence support Control better Intervention better
11 NPEP Research Priorities AccessUnderstanding barriers to accessing PEP for all population groupsDrug choiceResearch to inform future drug choices for adults, adolescents and childrenToxicity monitoringDrug-drug comparisonsResistance profiling / regimen selectionDrug – drug interactionsThe potential use of newer antiretrovirals ( DTG, RIL, EVG/cobi) for PEP.AdherenceOptimal adherence interventions – effectiveness, resource considerations, cost effectivenessImpact of pill burden on adherence to PEPFollow upOptimal testing strategies at follow upStrategies and impact of transitioning from PEP to PrEP
12 Finalisation and publication Next stepsDraft guidelinesGDG reviewFinal Recs textExternal peer reviewSubmit to GRCFinalisation and publicationJULYEARLY AUGEND AUGUSTOCTPresentation on expected direction of PEP guidance
13 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 partnersSathyanarayanan 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)).WHOCoordination: 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).