Are You Ready for the ARV Revolution?

1. Are You Ready for the ARV Revolution? Transforming HIV Prevention September 14, 2011 Jim Pickett Director of Prevention Advocacy and Gay Men’s Health AIDS Foundation of Chicago

2. Today • Definitions • Who is IRMA? • Why do we need new prev tech? • Review of the science, from July ‘10 – July ’11, ongoing trials • Implications and NOW WHAT?

3. Definitions • ARV, ART, HAART • Microbicide • PrEP • Treatment • Treatment as Prevention • TLC+ • TNT

4. Who is IRMA? • Mission: support development of safe, effective, acceptable, and accessible rectal microbicides for all that need them • 1000+ advocates, scientists, funders, policymakers from 6 continents – S. America/Latin America and Nigeria chapters AFC secretariat

5. rectalmicrobicides.org Global context

6. Highly active moderated listserv, website, blog, Facebook, Twitter, teleconferences

7. English, Spanish, French, Russian and Chinese rectalmicrobicides.org

8. Condoms work. So why do we need new strategies to halt the sexual transmission of HIV?

9. Here are some reasons for new strategies Source: Roger Tatoud PhD, Senior Programme Manager, International HIV Clinical Trials Research Mgmt Office, Imperial College London & IRMA Steering Committee Member

11. And here are some more Source: Measure Evaluation. 1997–2002. http://www.measuredhs.com

12. Intimacy Connection Emotion Pleasure

13. Prior to exposure Point of transmission Treatment What if we had a complete prevention tool kit? Improved ARV therapy Treatment for opportunistic infections Basic care/nutrition Prevention for positives Education & rights-focused behaviour change Therapeutic vaccines • Rights-focused behaviourchange • Voluntary counselling and testing • STI screening and treatment • Male medical circumcision • Preventive Vaccines • Pre-exposure prophylaxis (PrEP) • Male and female condoms and lube • ARV treatment to prevent vertical transmission (PMTCT) • Clean injecting equipment • Post-exposure prophylaxis (PEP) • Vaginal and rectal microbicides ARV = antiretroviral

14. The prevention landscape has forever changed

16. Let’s review the science • CAPRISA 004 • iPrEx • FEM PrEP • HPTN 052 • Partners PrEP • TDF2 (CDC 4940) Shall we?

17. CAPRISA 004 – July 2010

19. iPrEx – November 2010

20. *Only about half the men took their pills

21. New data on iPrEx • 2,499 HIV-negative gay men and other MSM • Brazil, Ecuador, Peru, South Africa, Thailand, US • Daily Truvada (FTC/TDF) • 92% efficacy among men with detectable drug levels • Overall efficacy down to 42% (from 44%)

22. New data on iPrEx • Adherence! • Drug levels in hair sub-study • Drug detected 90% of subjects from USA , RSA • Drug detected 55% of subjects from SA, Thailand • Acute infection/resistance • 10 infected acutely at start of PrEP, 2 of them developed resistance • Risk compensation - ?

23. Fem PrEP – 2011

24. But what about FEM PrEP? • Phase III, multi-center, double-blind, randomized, placebo-controlled effectiveness and safety study to assess the role of Truvada in preventing HIV acquisition in women • 1,951 women Kenya, South Africa, Tanzania • Study discontinued April – futility • HIV infection endpoints: 56 (78% of 72) – Truvada arm: 28, Placebo arm: 28 • Final data Q4 2011

25. HPTN 052 – 2011

26. HPTN 052 • Results first released May, “official” at IAS • Phase III clinical trial to eval effectiveness of ART to prevent sexual transmission of HIV in serodiscordant couples • Two study arms • 1) immediate initiation of ART in HIV-infected partner upon enrollment • 2) delayed initiation ART in HIV-infected partner until 2 consecutive CD4 cell counts were at or below 250 t-cells or AIDS-defining illness

27. HPTN 052 • 1,763 HIV serodiscordant couples enrolled between April ‘05 – May ‘10 • 886 couples randomly assigned immediate ART arm • 877 were randomly assigned delayed ART arm • Malawi, Zimbabwe, Botswana, Kenya, South Africa, Brazil, Thailand, US, India • 97% of the partnerships heterosexual

28. HPTN 052 • Early initiation ART led to 96% reduction in HIV transmission to HIV- partner • 105 morbidity and mortality events noted, with 40 in immediate ART arm, and 65 in delayed ART arm, showing trend toward benefit favoring immediate arm • Among endpoints, 3 extra-pulmonary tuberculosis events in immediate, and 17 in delayed

29. HPTN 052 This is the first randomized clinical trial to definitively indicate that an HIV-infected individual can reduce sexual transmission of HIV to an uninfected partner by beginning antiretroviral therapy sooner. – Myron Cohen, PI

30. Partners PrEP – 2011

31. Partners PrEP • Tenofovir, Truvada, placebo • HIV-serodiscordant couples • Once daily dosing • 4,758 HIV-serodiscordant couples • 60% couples male HIV-, 38% couple female HIV- • Kenya, Uganda • University of Washington, Bill & Melinda Gates Foundation, Gilead Sciences

32. Partners PrEP • Overall: TDF = 62% reduction, FTC/TDF = 73% • TDF efficacy • 68% fem, 58% men vs. placebo • FTC/TDF efficacy • 62% fem, 83% men vs. placebo • All differences “not statistically significant”

33. Partners PrEP • High adherence – 97% across all arms • Self reports correlate with pill count • Higher in couples? • No significant safety concerns • Recently closed placebo arm • Placebo arm offered either • Active drug arms remain blinded

34. Partners PrEP This is an extremely exciting finding for the field of HIV prevention. Now, more than ever, the priority for HIV prevention research must be on how to deliver successful prevention strategies, like PrEP, to populations in greatest need. –Dr. Jared Baeten, study co-chair

35. TDF2 (CDC 4940) – 2011

36. TDF2 (CDC 4940) • Bostwana – 1,219 neg het men/women aged 18 – 39 (46% women) • Once-daily dosing Truvada vs. placebo • 63% overall efficacy • 78% overall efficacy if only counting people who had been to clinic in last month • Adherence by pill count – 84% • No significant safety concerns • All offered open label

37. TDF2 (CDC 4940) These are exciting results for global HIV prevention. We now have findings from two studies showing that PrEP can work for heterosexuals, the population hardest hit by HIV worldwide. Taken together, these studies provide strong evidence of the power of this prevention strategy. – Kevin Fenton, director CDC National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention

38. We now have a solid scientific foundation to say that even in the absence of a vaccine we have the capacity to end the epidemic. I can’t go to the US President and say: 'We can cure HIV.’ But I can say ‘Ending the epidemic is scientifically doable’. –Tony Fauci, Director National Institute of Allergies and Infectious Diseases (NIAID)

39. Trials underway

40. VOICE/MTN 003

41. VOICE/MTN 003

42. VOICE/MTN 003

43. VOICE/MTN 003

44. FACTS 001

45. Overview of FACTS 001 • FACTS 001 will be similar to CAP004. • It is designed as a confirmatory study and is placebo controlled. • Study will test BAT24 dosing of tenofovir gel. • A minimum of 2,200 women will be enrolled at 9 sites across South Africa. • Study will enroll young HIV-negative women aged 18-30. • Study scheduled to start in Sept./October and last around 2 and half years.

46. PrEP studies underway

47. PrEP studies underway

48. Rectal snapshot

49. RM research activities • Baseline studies • What normally happens during AI? • Formulation studies • How will different chemicals and substances be put together to make a safe, effective RM? • Distribution studies • Where do RMs need to go?

50. RM research activities • Acceptability & behavioural studies • What kinds of products would people use? • Who is having AI? • Pre-clinical/basic science • developing and testing products in labs and in animal studies • Clinical trials – safety and efficacy • Are these RMs safe? Do they work?