1. Topical, Oral; Daily, Intermittent; Single, Combination agents; What do we need AND what will work? Patrick Ndase, Microbicide Trials Network & Dep’t of Global Health, University of Washington

2. Within the research & advocacy community, there is a lot of enthusiasm & hope around the promise of ARV-based approach to HIV prevention –Biomedical piece that will likely revolutionalize HIV prevention THE BOLD STATEMENT

3. WE NEED Topical AND Oral ARV-based intervention –Know your HIV status = Know your options Daily dosing as a 1 st step but Intermittent dosing based on exposure times preferred Single agents if efficacious & out of treatment realm desired, but the search for combination agents ought to continue

4. Key stakeholders’ question has been……. How can you explain the enthusiasm around ARV based prevention, amidst ever diminishing slots for people in desperate need of care? –Shall funders have the much needed momentum for prevention in light of failed sustained momentum for treatment? –Can’t the biomedical prevention approach be mismanaged?

5. Reminder of why we need additional prevention tools now For every 2 people started on ART in Southern Africa, 3 become newly infected In South Africa alone >1500 new HIV infections are Estimated to occur daily An approx 70,000 babies are born with HIV annually Bottom line: We need to prevent new infections if we’re to effectively treat those who need care. http://www.avert.org/aidssouthafrica.htm

6. The Face of HIV in Uganda 110,000 new infections every year (> 300 new infections everyday) 73,000 (66%) of new infections annually are women. 47% of the women living with advanced have no access to anti- retroviral therapy 52% percent access PMTCT (21% of new infections due to MTCT)

7. The New York Times on Uganda At Front Lines, AIDS War Is Falling Apart ~ 500,000 need treatment 200,000 getting treatment Each year approx an additional 110,000 infected

8. HIV slots not only limited to Uganda Economy Hurts Government Aid for H.I.V. Drugs, New York Times of June 30 th, 2010 FORT LAUDERDALE, Fla. Nearly 1,800 have been relegated to rapidly expanding waiting lists that less than three years ago had dwindled to zero. http://www.nytimes.com/2010/07/01/us/01aidsdrugs.html?hp

9. Proving the skeptics wrong ART roll-out in resource limited settings will never be possible –Countries now constrained with stock-outs & few slots for new entrants Adherence to ART will be poor in the developing world –Some of highest reported adherence rates –Resistance a major worry due to programmatic failure (NOT poor adherence)

10. Signal of willingness to access prevention services Documented HIV Prevalence on Island is 17% [2006 Sentinel survey] Having sex is single most important risk factor in context of high prevalence Up to 5hrs en-route study clinic for PrEP Participants wake up 3:00AM to start journey Yet with excellent retention

11. Topical, Oral; Daily, Intermittent; Single, Combination agents; What do we need AND what will work?

12. Is the field poised to provide all we need? Vaccine - Prime/Boost Thailand Oral TDF - IDU Thailand Oral Truvada – Heterosexual Botswana Oral TDF -MSM US (Ph II) Oral Truvada - MSM (iPrEx) Oral TDF, Truvada - Partners PrEP Oral Truvada - FemPrEP Microbicide - BufferGel, PRO2000 CAPRISA 004 TDF Gel Microbicide - PRO2000 Oral TDF & Truvada & Tenofovir gel - VOICE Microbicide - Dapivirine gel & ring 2009 2010 2011+ Index Partner Treatment HSV-2 Treatment - Infectiousness 2015+ New Vaccine concept(s) Vaccine - DNA Prime/Ad5 Boost US TMC 278 - UK (Ph I/II) Microbicides PrEP Vaccines Treatment as PX KEY Testing & linkage to care plus (TLC+)

13. What will be lacking? Topical / OralVOICE efficacy & acceptability data will be critical Daily / IntermittentNo data on intermittent use & efficacy A hint from CAPRISA’s coitally dependent approach Single / Combination agentsOral: TDF/Truvada will provide a hint No topical combinations The three issues here all point to efficacy; QUESTION: But how much of an impact does efficacy have on the epidemic?

14. Use Microbicides/ PrEP 50% Product 50% effective Product 80% effective 100 Women Exposed to HIV (10% transmission risk) 50 have access TOTAL The Prvention Cascade – 50% Access/Adherence Access to Microbicides/ PrEP 50% 50 have no access 25 use 75 do not use 1.3 infections 0.5 infections 7.5 infections 7.5 infections If 50% − 9 infections If 80% − 8 infections No Product − 10 infections

15. Use Microbicides/ PrEP 95% Product 50% effective Product 80% effective 100 Women Exposed to HIV (10% transmission risk) 95 have access TOTAL The Microbicide/PrEP Cascade – 95% Access/Adherence Access to Microbicides/ PrEP 95% 5 have no access 90 use 10 do not use 4.5 infections 1.8 infections 1 infection 1 infection If 50% − 6 infections If 80% − 3 infections No Product – 10 infections

16. The prevention Cascade Intervention effectPercent coverageFraction of Infections prevented 80%50%20% 50%95%40% The effectiveness of an intervention, matters but coverage matters even more

17. Impact of ARV-based prevention on epidemic Modeling work (Imperial College London) Targeting most at-risk populations Extent of coverage of these populations Adherence/Acceptability of the interventions

18. An old challenge! Can we deliver on the promise? Sources: UNAIDS, 2004; UNGASS, 2008; WHO, 2009 0% 20% 40%60%80%100% HIV testing Antiretrovirals for PMTCT Condom Use Contraception for PMTCT 2004 9%32% 9% 14% 2006/7 Male Circumcision 20% 80% 85% 10% 75% 55% Unmet HIV Prevention Need 85% Estimates of CoverageUnmet Need for HIV Prevention 5% 15% 2008 45% 39% 25%

19. Thank You The International Clinical Research Center at UW The Microbicide Trials Network