Update on PrEP progress: WHO/UNAIDS challenges and actions Kevin R. O'Reilly Prevention in the Health Sector, HIV/AIDS Department, WHO HQ
Outline Review current status of PrEP Planning for PrEP
Pre-exposure prophylaxis (PrEP) In PrEP, an HIV uninfected individual takes antiretroviral medication(s) daily. By having these medications in the bloodstream, HIV may be unable to establish infection. Evidence that PrEP may work to prevent HIV Animal studies PMTCT PEP
Considerations re TDF & FTC/TDF for PrEP POTENT: Broad antiviral activity (HIV-1 subtypes, HIV-1&-2) Active against virus types found both in early and late HIV infection (i.e., R5 & X4 viruses) Acts early in the life cycle of HIV (pre-integration) so it can block initial infection Rapidly active (suggesting even intermittent use might be possible) SAFE: Favorable safety and tolerability High barrier to resistance, and limited cross-resistance EASY: Relative easy to use (low pill burden, no food restrictions, no drug interactions with contraception/tb meds/antibiotics) We are evaluating both TDF and FTC/TDF because of the potential for different cost, resistance, and efficacy
Ongoing and Planned Efficacy Trials of PrEP USA Thailand Brazil Ecuador Peru Botswana Kenya Malawi South Africa Tanzania Uganda Zambia Zimbabwe 7 efficacy studies, up to 13 countries 20,000+ participants
CDC PrEP Studies Location Population PrEP Intervention Status United States phase II study 400 men who have sex with men TDF Enrollment began February 2005 Fully enrolled Results late 2009/early 2010 (safety & risk behavior)
CDC PrEP Studies Location Population PrEP Intervention Status United States phase II study Thailand (Bangkok Tenofovir Study) 400 men who have sex with men 2400 injection drug users (~20% women) TDF Enrollment began February 2005 Fully enrolled Results late 2009/early 2010 (safety & risk behavior) TDF Enrollment began June 2005 ~95% enrolled Results 2010-2011 Interim efficacy review October 2009; recommended study continuation
CDC PrEP Studies Location Population PrEP Intervention Status United States phase II study Thailand (Bangkok Tenofovir Study) Botswana (TDF2 Study) 400 men who have sex with men 2400 injection drug users (~20% women) 2400 heterosexual men and women TDF Enrollment began February 2005 Fully enrolled Results late 2009/early 2010 (safety & risk behavior) TDF Enrollment began June 2005 ~95% enrolled Results 2010-2011 Interim efficacy review October 2009 FTC/TDF Enrollments began March 2007 <50% enrolled Results 2012 (?)
CAPRISA 004 Location Population PrEP Intervention Status South Africa phase II study 900 high-risk women Vaginal TDF gel (coitallydependent) Enrollments began July 2007 Fully enrolled One interim efficacy review completed; results expected mid- 2010 Funder: USAID, FHI, CONRAD
iprex Location Population PrEP Intervention Status Brazil Ecuador Peru South Africa Thailand United States 3000 men who have sex with men FTC/TDF Enrollments began July 2007 ~2300 enrolled Results expected 2010-2011 Interim efficacy review November 2009 recommended continuation Funders: US NIH + BMGF
Partners PrEP Location Population PrEP Intervention Status Kenya Uganda 3900 HIV serodiscordant couples TDF FTC/TDF Enrollments began July 2008 ~2700 enrolled Results expected Q4 2012 Funder: BMGF to University of Washington Study Drug provided by Gilead
FEM-PrEP Location Population PrEP Intervention Status Kenya South Africa Site development ongoing (Malawi, Tanzania, Zambia) 3900 high-risk, heterosexual women FTC/TDF Enrollments began May 2009 ~250 enrolled so far Results ~2012-13 Funders: USAID + BMGF (to FHI)
VOICE Trial Location Population PrEP Intervention Status Uganda Zimbabwe Site development ongoing (Malawi, South Africa, Zambia) 5000 heterosexual women TDF FTC/TDF Vaginal TDF gel (5 arm study: including oral and vaginal placebo groups) Enrollments began September 2009 Results ~2012-13 Funded by the National Institutes of Health: NIAID, NICHD and NIMH through the Microbicides Trial Network In partnership with Gilead and CONRAD
Outline Review current status of PrEP Planning for PrEP
Goal: moving PrEP from trial effectiveness to real world effectiveness Frustration with prevention runs high debatable if this is justified Optimism about PrEP runs higher animal models promising well-designed trials underway some evidence could be forthcoming Experience of moving from trials to implementation effectiveness is usually less than efficacy implementation usually more complicated than planned pace of scale-up usually much longer than expected
Reality check Thorny issues to be addressed include so far only proof of concept through animal data implementation challenges could limit effect cost of daily PrEP (greater than treatment?) motivation for daily PrEP attractiveness of intermittent PrEP though much longer lead time to results political challenge of advocating scarce resources for socially marginalized groups sex workers, MSM, IDU readily available drug
Reality check: Setting the tone Envision a broader approach where PrEP is integrated into current HIV prevention programs PrEP will not be a magic bullet
3 key phases of WHO/UNAIDS Phase I workplan on PrEP Bridging between science and implementation Phase II Consensus recommendations Phase III Helping countries decide if, when and how to implement Support countries in implementation Positive trial results become available WHO/UNAIDS make official statement Efficacy is sufficiently established Phase I: Bridging between science & implementation Phase III: Endorsement, guidelines & technical assistance for scale up Phase II: Consensus recommendation meeting
WHO PrEP implementation plans: strands in the Gordian knot I Reaching Consensus on Global Recommendations Close planning with Guidelines Review Committee What is sufficient evidence for WHO? Solving the puzzle of efficacy, side effects, drug safety, choice of target groups and epidemic settings Regulatory& Licensing processes. Manufacturing capacity II III Health Systems Users Issues Addressing PrEP-specific issues HIV testing & counselling, drug resistance and re-testing Adverse Events (e.g. Renal dysfunction, hepatitis flares) Pregnancy, breast feeding System strengthening: Infrastructure, financial and human resources capacity Adding PrEP to existing prevention, care and treatment priorities User and community acceptability for a daily prevention method Adherence Risk compensation Drug sharing Social issues Safety issues
What WHO will need to endorse PrEP Careful planning & close cooperation with the Guidelines Review Committee Evidence of efficacy from more than one trial depends on which ones, where, target populations, etc. the stronger the evidence the better Independent review of the data from the trials Endorsement: breadth linked to strength and generalisability of results may influence how much additional evidence is needed, or how generalisable the results may be across regions and populations
WHO/UNAIDS-led Steering Committee Existing Working Groups Research Focused Other Necessary Working Groups & work packages Implementation Focused PrEP Trialists' Working Group (Forum for Collaborative HIV Research) PrEP Communication Working Group (Facilitated by AVAC) Steering Committee PrEP Implementation/ delivery Working Group GRC approval process Planning & Implementation Regulatory & Licensing Drug costing & forecasting