1. Monica Gandhi MD, MPH Associate Professor and Women’s HIV Clinic provider, HIV/AIDS Division San Francisco General Hospital/ UCSF Safe Poz Love, U.S. Positive Women’s Network February 14, 2012 Science and Sex: HPTN 052 and Treatment as Prevention

2. Percent of adults (15+) living with HIV who are female, 1990–2009 Sub-Saharan Africa GLOBAL Caribbean Asia E Europe & C Asia Latin America www.unaids.org

3. Proportion of all AIDS cases in women: 7% in 1985 to 26% today

4. We already thought HIV-positive people on antiretrovirals cannot pass on the virus readily –The lower your HIV viral load in plasma, the lower the viral load in semen and vaginal secretions –Concentration of HIV in the genital area correlates with sexual transmission –Observational studies had shown very low rates of transmission to sexual partners if HIV-infected person is on treatment –But in MEDICINE, “evidence” means a randomized controlled trial

5. Cohen MS et al. Prevention of HIV-1 infection with early antiretroviral therapy. NEJM August 2011 (HPTN-052)

6. Stable, healthy, serodiscordant couples, sexually active CD4 count: 350 to 550 cells/mm 3 Primary Transmission Endpoint Transmission events that were linked to that primary partnership Primary Clinical Endpoint WHO stage 4 clinical events, pulmonary tuberculosis, severe bacterial infection and/or death HPTN 052 Study Design Immediate ART CD4 350-550 Delayed ART CD4 <250 Randomization

7. 10,838 Individuals Screened Immediate Arm 886 Couples Delayed Arm 877 Couples Major reasons for exclusion: 3058 HIV+ but CD4 count out of range 2565 HIV- but HIV+ partner ineligible 308 Seroconcordant couples 155 Ineligible due to sexual history HPTN 052 Enrollment 1763 Couples (3526 Individuals) Randomized

8. HPTN 052 Enrollment (Total Enrollment: 1763 couples) U.S. Brazil South Africa Botswana Kenya Thailand India Americas 278 Africa 954 Asia 531 Zimbabwe Malawi

9. IndexPartner Immediate N = 886 Delayed N = 877 Immediate N = 893 Delayed N = 882 Female49%50%49%47% Age (median)3332 Married94%95%93%94% Any unprotected sex6%8% CD4 (median [IQR]) 442 [373-522] 428 [357-522] --- HIV RNA log 10 (median [IQR]) 4.4 [3.8-4.9] 4.4 [3.9-4.9] --- HPTN 052: Baseline Characteristics

10. “ The Board recommends that the results of the trial be announced as soon as possible” (was supposed to go until 2014) HPTN 052 continues to follow couples, but all HIV-infected participants are being offered ART The Data safety and monitoring board announced April 28, 2011

11. Total HIV-1 Transmission Events: 39 HPTN 052: HIV-1 Transmission Immediate Arm 4 Delayed Arm 35 p < 0.0001

12. Total HIV-1 Transmission Events: 39 HPTN 052: HIV-1 Transmission Linked Transmissions: 28 Unlinked or TBD Transmissions: 11 p < 0.001 Immediate Arm: 1 Delayed Arm: 27 23/28 (82%) transmissions in sub- Saharan Africa 18/28 (64%) transmissions from female to male partners 238 pregnancies People have sex outside of their partnerships.. Wait, REALLY????!!! People have unprotected sex. Wait, REALLY????!!!

13. 0.1/1.7 = 96% reduction Study ArmFollow-up (PY)* Incidence/100PY [95% CI] LinkedOverall Immediate1585 0.1 [0.0 – 0.4] 0.3 [0.1 – 0.6] Delayed1567 1.7 [1.1 – 2.5] 2.2 [1.6 – 3.1] HPTN 052: HIV-1 Transmission *Person-years specific for transmission events

14. HPTN 052: Effect of ART Immediate Arm Delayed Arm (not on ART) Delayed Arm (on ART) 3691215182124273033363942450 Months Proportion of participants with VL<400 at each visit 60 80 100 40 20 0

15. One Transmission Event on ART Single Genome Analysis: 1-2 viruses transmitted Analysis of Transmission: >50 days earlier (84 – 190 days) -14 Screening Days0 Enrollment 1 Index begins ART AZT/3TC/EFV 28 Index VL<400 85 Partner HIV+ (WB) Partner VL < 400 Index CD4 = 482 Index VL = 87,202

16. HPTN 052 Prevention Conclusion Early ART that suppresses viral replication led to 96% reduction of sexual transmission of HIV-1 in serodiscordant couples

17. Sex and sexuality for HIV-positive women With such strong evidence for protection and prevention, let’s think about sexual rights in women living with HIV infection!