1. Women and ARV-based Prevention: Challenges and Opportunities Tim Mastro, MD, DTM&H AIDS 2014 Melbourne, Australia 24 July 2014

2. Women and Risk for HIV Infection 2 Women at risk due to complex mix of biological, behavioral, structural, cultural and social factors Varying risk Young women in Africa at particular risk HIV incidence: 4% to 9% per year in recent studies, despite best available HIV prevention Risk perception often low, despite high rates of HIV

3. Age Group (Years) HIV Prevalence (N=1237) ≤1610.6% 17-1821.3% 19-2033.0% 21-2244.3% 23-2451.1% HIV prevalence in pregnant women in rural Vulindlela, South Africa

4. Structural Interventions Medication assisted therapy for people who use drugs Clean injection equipment for people who inject drugs PMTCT ARV PrEP Behavioral Interventions HIV Testing and Counselling Male & female condoms Blood Supply Screening Male circumcision ART – Treatment as Prevention Treatment of STIs COMBINATION HIV Prevention

5. Approaches to Reducing HIV Transmission Exposure to HIV INFECTED PARTNER Reduce infectiousnessReduce susceptibility Reduce exposure HIV+HIV- EXPOSED PARTNER

6. HIV Suppression Stops Transmission 6 96% HPTN 052: If an HIV-infected person adheres to ART, the risk of transmitting the virus is reduced by 96% UNAIDS 2011 AIDS at 30 SMARTER, FASTER, BETTER CAMPAIGN “HPTN 052 is a game changer” Michel Sidibe, Executive Director of UNAIDS

7. ART Coverage and HIV Incidence, KwaZulu Natal, South Africa 7 Africa Centre, Univ of KwaZulu Natal Africa’s largest population-based cohort study; >16,000 HIV-negative people followed, 2004-11 HIV incidence decline associated with increased ART coverage Communities with 30-40% ART coverage had 38% lower HIV incidence than communities with <10% ART coverage Tanser F, Science, Feb 2013

8. HIV prevention, care and treatment cascade – major gaps in operational guidance Viral suppression People aware of HIV status on ART All people Reached by prevention in the health sector Enrolled in HIV care HIV+ HIV- Prevention targeting HTC demand creation Referral Retained Prevention opportunities for negatives Prevention opportunities for PLWHIV, care and treatment for PLWHIV HIV+ HIV-

9. Effectiveness in HIV Prevention Trials 9 Efficacy Study Effect size (CI) TDF/FTC oral PrEP (iPrEx, 2010) 44% (15, 63) TDF oral PrEP (Partners PrEP, 2011) 62% (34, 78) 0% 20 40 60 80 100% 63% (22, 83) TDF/FTC oral PrEP (TDF2, CDC, 2011) Medical male circumcision (x3) (Orange Farm, 2005; Rakai, Kisumu, 2007) 57% (42, 68) Prime-Boost vaccine (Thai RV144, 2009) 31% (1, 51 ) 1% tenofovir gel (CAPRISA 004, 2010) 39% (6, 60) TDF/FTC oral PrEP (Partners PrEP, 2011) Immediate ART for HIV-positive partners (HPTN 052, 2011) 73% (49, 85) 96% (82, 99) TDF oral PrEP (CDC, IDU, 2013) 49% (10, 72)

10. 10 Challenges

11. Effectiveness in HIV Prevention Trials 11 Efficacy Study Effect size (CI) TDF/FTC oral PrEP (iPrEx, 2010) 44% (15, 63) TDF oral PrEP (Partners PrEP, 2011) 0 - 62% (0, 78) 0% 20 40 60 80 100% 63% (22, 83) TDF/FTC oral PrEP (TDF2, CDC, 2011) Medical male circumcision (x3) (Orange Farm, 2005; Rakai, Kisumu, 2007) 57% (42, 68) Prime-Boost vaccine (Thai RV144, 2009) 31% (1, 51 ) 1% tenofovir gel (CAPRISA 004, 2010) - 39% ( 60) TDF/FTC oral PrEP (Partners PrEP, 2011) Immediate ART for HIV-positive partners (HPTN 052, 2011) 0 - 73% (0, 85) 96% (82, 99) (VOICE, 2011) (FEM-PrEP, 2011; VOICE, 2013) 0 0, 0, TDF oral PrEP (CDC, IDU, 2013) 49% (10, 72)

12. Pearson correlation = 0.86, p=0.003 Effectiveness by adherence Source: Salim S. Abdool Karim, personal communication

13. Summary of PrEP Trials for Women 13 Tenofovir gel safe & effective in CAPRISA-004 (BAT-24 dosing). But, not effective in VOICE (daily dosing) FACT 001 (BAT-24) ongoing, results in 2015 TDF/FTC (daily) effective and well tolerated: – For hetero men & women in CDC TDF2 and Partners PrEP (also showed TDF effective) – But, not effective for women in FEM-PrEP and VOICE (low adherence) Demonstration programs ongoing, or planned

14. 14 Opportunities

15. Long-acting ARV Products 15 Dapivirine (NNRTI) vaginal ring; monthly ASPIRE (MTN 020) & IPM RING Study ongoing Expect results in 2015 Vaginal rings – multipurpose prevention Injectable, long-acting agents – 1-3 monthly TMC278 LA (rilpivirine, NNRTI) GSK744LA (integrase inhibitor)

16. Issues for ARVs for Prevention 16 Who will use PrEP? For what phase(s) of life? For how long? Who will pay? Intermittent dosing? Adherence Service delivery Reproductive health needs Many, many more………..