1. HIV-infected subjects with CD4 350 to 550 cells/mm 3 1763 serodiscordant couples HPTN 052 Study Design Immediate ART CD4 350-550 Delayed ART CD4 <250 Randomization N = 886 N = 877 184 initiated therapy during the trial REF: Cohen MS, et al. N Engl J Med 2011. All 886 initiated therapy at the start

2. Total HIV-1 Transmission Events: 39 HPTN 052 results Linked Transmissions: 28 Unlinked or TBD Transmissions: 11 p < 0.001 Immediate Arm: 1* Delayed Arm: 27 64% transmissions (tx) from HIV+ w/ CD4 >350 cells/µL & VL >50,000 c/mL 82% (23) tx from sub-Saharan Africa ♀♂ 64% (18) tx from ♀ to ♂ partners Cohen MS, et al. N Engl J Med 2011. * Tx likely near time of cART initiation

3. 96% reduction in the risk of transmission to sexual partners “HPTN 052 is a game changer” Michel Sidibe Executive Director of UNAIDS Note: adherence to cART was very high in this well-funded RCT How do we pull this off in the real world “How do we pull this off in the real world?” Jim Shelton Science 2011 HIV Suppression Stops Transmission

4. ACTG 076 IOM Committee on Perinatal Transmission of HIV Wortley PM, et al. Successful implementation of perinatal HIV prevention…. MMWR 2001 Lansky A, et al. Trends in HIV testing among pregnant women….Am J Public Health. 2001 Lindegren ML, et al. Trends in perinatal transmission of HIV/AIDS in the US. JAMA. 1999

5. New HIV infections among children, 1990-2007 (2008 UNAIDS) Still, >1000 babies infected with HIV every day: 370,000 in 2009, 98% in LMICs HIVNET 012 UNAIDS 2010

6. Testing and linkage to care Test HIV + Adopt safer behaviors Enroll in Care Treat Maintain viral suppression Positive Prevention Testing Initiation of ART Linkage to care sites Adherence to ART Decrease in HIV Transmission

7. Aspiration Meets Reality Treat to prevent: Aspiration Meets Reality 77% 66% 66% 89% 77% Multiplies to 28% Only 28% of HIV+ Americans had optimal suppression in 2010 Refs: Gardner, Clin Inf Dis 2011  MMWR 2011 80%

8. Aspiration Meets Reality 77% 66% 89% 77% Multiplies to 28% 80% MORE TESTING BETTER LINKAGE INCREASE RETENTION EARLY cART INCREASE ADHERENCE

9. Testing and linkage to care Test HIV + Adopt safer behaviors Enroll in Care Treat Maintain viral suppression Positive Prevention Testing Initiation of ART Linkage to care sites Adherence to ART Decrease in HIV Transmission Co-morbidities lead to: Increased transmission Less testing Less linkage Less retention Less treatment Less adherence Less VL suppression

10. Primary Prevention Efforts PrEP, PEP, condoms, syringes Drivers 1.Substance use 2.Alcohol 3.Meth 4.Crack 5.Poppers 6.STDs, # of partners  Testing Diagnosis Primary Care  Treatment Virologic Suppression Linkage HIV Engagement / Retention High income settings: Maximizing the HIV Prevention, Care and Treatment Continuum  Community Testing  Linkage & Partner Services Mental Health Services Substance Use Treatment Housing Support Treatment Adherence Medical Case Management  Routine Medical Testing SFDPH Positive Health Access to Services and Treatment (PHAST) STD & PCSI ART Guidelines Uptake Engagement & Partner Services REF: Das M, et al. PLoS One 2010

11. HPTN 071 - PopART Study Population effect of universal testing and immediate ART therapy to Reduce HIV Transmission

12. Universal voluntary HIV testing with appropriate combination prevention offered to all those testing HIV negative - in addition to immediate ART for all those testing HIV positive - will have a substantial impact on HIV incidence at population level Hypothesis

13. Universal voluntary annual home-based HIV testing Linkage to care (local health center) for those testing HIV(+) Immediate ART offered to those testing HIV positive Voluntary medical male circumcision for men testing HIV(-) Strengthening and promoting PMTCT services Syndromic STI treatment at clinic Drug and alcohol use assessment Counseling and condom provision in the community The PopART Combination Intervention Package Community HIV Providers (CHiPs) to deliver testing, counselling, linkage to care, & treatment support in the community

14. Trial Design: three-arm, two- country, cluster-randomized 21 clusters (communities): 12 in Zambia, 9 in So. Africa Average of ~50,000 in each cluster; 50% are adults Incidence measured in Population Cohort: 2,500 adults in each cluster, followed up yearly for 3 years Arm A (7 sites) Arm B (7 sites) Arm C (7 sites) Full PopART PopART, but CD4<350 Standard of Care

15. HPTN 071/PopART Study Design: A 3-Arm, 2-Country Cluster Randomized Trial A B C A B C A B C A B C A B C A B C A B C Zambia South Africa 15-30,000 adults in each community Enroll 2.500 into Population Cohort

16. Study Locations: 12 communities in Zambia 9 communities in the Western Cape of South Africa Zambia South Africa

17. Primary Objective –To measure the impact of the PopART intervention in reducing HIV incidence –Measured in a cohort of 52,500 adults over 3 years Secondary Objectives –Uptake of intervention components –Retention in HIV care –Sexual risk behavior –HIV-related stigma –HIV disease progression and death –TB case notification rate –HSV-2 incidence –ART Toxicity –ART adherence and viral suppression * –Community viral load* –ART drug resistance* *if further funding obtained Objectives