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

DHHS/NIH/OAR HIV/AIDS in Women in DC 2009 (2.7%) (DC DOH) RaceRate/100K Black2,826.4 Hispanic/Latina785.0 White153.4 Other862.6 Total1692.4

DHHS/NIH/OAR WHAT IS NEW IN HIV PREVENTION RESEARCH? What is new in HIV prevention research?

DHHS/NIH/OAR Understanding Women’s Risk for HIV

DHHS/NIH/OAR 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

DHHS/NIH/OAR Do hormones affect HIV risk? Partners in Prevention study Hormonal contraception (injectable) Serodiscordant couples HIV neg women / infected male partner Hazard Ratio -- HIV acquisition– HIV neg man / infected female partner Hazard Ratio -- HIV acquisition– 1.95 Genital VL X Heffron, Lancet ID, 2012

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

DHHS/NIH/OAR ARE THERE INTERVENTIONS TO DECREASE HIV RISK? Are there interventions to decrease HIV risk?

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

DHHS/NIH/OAR Microbicides – CAPRISA - 004: Effectiveness of 1% tenofovir gel in preventing HIV and HSV infection 1% tenofovir Gel Placebo Number of HIV infections 3860 Number of HSV-2 infections 2958 Karim Q. et al. Science 2010, 329: % lower HIV incidence overall (54% incidence with > 80% adherence) 51% lower HSV-2 incidence overall

DHHS/NIH/OAR 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

DHHS/NIH/OAR FemPrEP Daily 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

DHHS/NIH/OAR 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

DHHS/NIH/OAR Partners PrEP Study 4,758 HIV serodiscordant couples randomized to receive tenofovir, tenofovir + emtricitabine (Truvada) or placebo Kenya and Uganda tenofovirTruvadap value Overall62%73%.0003 Female68%62%.01 Male55%83%.001 IAS 2011, Plos One 2011

DHHS/NIH/OAR HPTN 052: Treatment as Prevention Ongoing study with interim report HIV serodiscordant heterosexual couples HIV-infected partner --- CD4 count 350 to 550cells/µL Early Treatment CD cells/ul Delayed treatment CD4 -- < 250 cells/ul Efficacy96%, p =.0001 Transmission events 127 OIs and clinical events 4065 Extra Pulmonary TB events 317 Cohen, Science 2011

DHHS/NIH/OAR MTN VOICE Trial Vaginal 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

DHHS/NIH/OAR 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

DHHS/NIH/OAR 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 about the effect of hormones ? Rectal microbicides Behavioral and social norms

DHHS/NIH/OAR 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?

DHHS/NIH/OAR 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

DHHS/NIH/OAR 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

DHHS/NIH/OAR Annual Trans-NIH Plan for HIV-Related Research: Ensuring research priorities reflect the needs of the field