HIV and Women Collaborating Across Borders to Advance the Health of Women IAS 2012

1. HIV and Women Collaborating Across Borders to Advance the Health of Women IAS 2012 Gina M. Brown, M.D. July 22, 2012

2. HIV/AIDS in Women in DC 2009 (2.7%)(DC DOH)

3. What is new in HIV prevention research? What is new in HIV prevention research?

4. Understanding Women’s Risk for HIV

5. Mucosal immunity and HIV risk • Natural protection-- adaptive and innate • Endogenous antimicrobials—antibacterial, antifungal, antiviral, cytokine induction, regulate antigen uptake • Microflora • pH • Endocrine effects--- impact risk • Ovulation – decreased -cytokine production/activity, SLPI • Pregnancy– antimicrobial/ anti-inflammatory alterations • Hormonal contraception • Semen Wira, AJRI March 2011, Herold 2012

6. Do hormones affect HIV risk? Partners in Prevention study Hormonal contraception (injectable) Serodiscordant couples 1314 -- HIV neg women / infected male partner Hazard Ratio -- HIV acquisition– 1.98 2476 HIV neg man / infected female partner Hazard Ratio -- HIV acquisition– 1.95 • Genital VL -- 1.67 X Heffron, Lancet ID, 2012

7. Do hormones affect HIV risk? Partners in Prevention Study Pregnancy nrnejjpjpifpjb Serodiscordant couples 1085 – HIV neg women / infected male partner HR -- HIV acquisition– 2.34 2236 HIV neg men / infected female partner HR -- HIV acquisition –2.31 Mugo, AIDS July 21, 2011

8. Are there interventions to decrease HIV risk? Are there interventions to decrease HIV risk?

9. 96% HPTN-052 Partners PrEP 73% CDC TDF2 63% Circumcision 54% iPrEX 44% STI 42% CAPRISA 39% RV144 31% Effectiveness of Prevention Abdool Karim & Abdool Karim. Lancet 2011

10. Microbicides – CAPRISA - 004: Effectiveness of 1% tenofovir gel in preventing HIV and HSV infection 39% lower HIV incidence overall (54% incidence with > 80% adherence) 51% lower HSV-2 incidence overall Karim Q. et al. Science 2010, 329:1168-1174

11. PrEP: iPrEX – Oral Pre-exposure Prophylaxis with Truvada (tenofovir plus emtricitabine) • Studied in MSM and transgender women who have sex with men • Once daily pill • Comprehensive package of HIV prevention services • 44% reduction in HIV seroconversion in Truvada group • 73% reduction with > 90% adherence • Study limitations Grant CROI 2011, NEJM 2012

12. FemPrEPDaily oral Truvada in heterosexual women • Discontinued for futility • Adherence was the issue? • 94% adherence by ACASI • 85% adherence by pill count • 43% adherence by drug levels • The questions • Pill count vs. drug levels? • Why the adherence issue? • Social and behavioral norms CROI 2012, NEJM 7/12

13. CDC Botswana TDF2 Study • 1,200 men and women randomized to Truvada or placebo • Botswana • 80% effective to prevent infection in men • Not powered to show a statistically significant effect in women IAS, July 2011

14. Partners PrEP Study • 4,758 HIV serodiscordant couples randomized to receive tenofovir, tenofovir + emtricitabine (Truvada) or placebo • Kenya and Uganda IAS 2011, Plos One 2011

15. HPTN 052: Treatment as PreventionOngoing study with interim report HIV serodiscordantheterosexual couples HIV-infected partner --- CD4 count 350 to 550cells/µL Cohen, Science 2011

16. MTN VOICE TrialVaginal and Oral Interventions to Control the Epidemic • 5000 women in South Africa, Uganda, and Zimbabwe • Daily dose • Oral tenofovir, or oral Truvada, vs. oral placebo • Vaginal 1% tenofovir gel vs. placebo gel • Oral tenofovir discontinued –due to no effect • Daily vaginal tenofovir gel discontinued due to no effect – HIV 6% vs. 6.1% • Daily oral Truvada study continues • Last study visit August, 2012 Sept, Nov 2011

17. HIV Prevention Issues for Women • Conflicting prevention trials data • 1% tenofovir gel • Preventive – CAPRISA 004 BAT 24 • Not preventive – VOICE daily dose • Oral Pre Exposure Prophylaxis • Couples vs. Singles • Preventive -- Partners PrEP • Not significant effect -- CDC TDF2 • Not preventive -- FemPrEP, VOICE • Treatment as prevention • Couples vs. singles

18. Unanswered questions in PrEP and microbicides studies • PrEP and ART resistance • Differential safety and efficacy between oral and topical PrEP • VOICE study • Use of microbicides and PrEP in adolescents • Use of microbicides and PrEP in pregnancy • When can we give up condoms? • PrEP and invasive procedures during pregnancy • What aboutthe effect of hormones? • Rectal microbicides • Behavioral and social norms

19. Where are we now with HIV prevention for women? • Male condoms • Female condoms ? • Treatment as Prevention? • Couples vs. general public • Availability for all? • Treatment success for all • PrEP –tenofovir/emtricitabine • FDA approved July 16, 2012 • Couples vs. general public • Availability? • Who prescribes?

20. HIV Prevention Research: What is on the Horizon? • FACTS – 001/002 (Follow on African Consortium for Tenofovir Studies) • 1% tenofovir gel before and after sex (repeats CAPRISA) in adult and adolescent women • ASPIRE– Dapivarine ring study • PrEP implementation pilot studies • FDA approval July 16, 2012 • Multi-purpose Prevention Technologies (MPTs) • Preventing HIV, STIs, Pregnancy • Sorting out hormonal contraception and HIV risk (CDC, Cochrane Collaborative) • New formulations and delivery systems

21. HIV Prevention Research: what is needed? • Basic sciences: risk, pathogenesis, and prevention • Vaginal and rectal ecology and functional immunity • Semen and risk • Other modulators – hormones? • Socio-cultural influences on risk • Informs prevention interventions • Behavioral and social norms • Risk across the lifecycle • Clinical research • Prevention– HIV and multi-purpose • Safe pregnancy • Adherence and safety markers • Male circumcision impact on women? • Formulations and delivery

22. Annual Trans-NIH Plan for HIV-Related Research: Ensuring research priorities reflect the needs of the field