1. ART for Prevention From Evidence to Action Wafaa El-Sadr, MD, MPH ICAP-Columbia University

2. The Evidence is Here! Ecological data Observational studies in discordant couples Randomized clinical trial (HPTN 052)

3. Number of PLWH receiving ART in low- and middle-income countries, by region, 2002–2009 UNAIDS, 2010

4. HIV Treatment Coverage in Low & Middle Income Countries WHO Towards Universal Access 2010

5. ART for Prevention Test HIV Positive Adopt safer behaviors Enroll in Care Treat Maintain viral suppression Positive Prevention Testing Initiation of ART Linkage to care Adherence to ART Decrease in HIV Transmission

6. ART for Treatment & Prevention Test HIV Positive Adopt safer behaviors Enroll in Care Treat Maintain viral suppression Positive Prevention Testing Initiation of ART Linkage to care Adherence to ART Decrease in HIV Transmission Optimal Treatment Outcomes

7. HIV Care Continuum HIV Diagnosis ART Monitoring and Retention in Care ART eligible Pre-ART Monitoring, Retention and Adherence Support

8. HIV Testing and Knowledge of HIV Status-- Kenya 84% of HIV-infected adults did not know their status. 16% knew they were positive 28% reported last HIV-test negative 56% never tested for HIV KAIS, 2008

9. Awareness of HIV Status Among Persons with HIV and Estimates of Transmission-- US ~21% Unaware of Infection ~75% Aware of Infection People Living with HIV/AIDS 1,106,400 New HIV Infections Each Year: ~56,000 ~54 - 70% of New Infections ~30 - 46% of New Infections Marks, et al AIDS 2006

10. Point of Entry into HIV care ICAP-Supported Programs VCTPMTCTPICTTB/HIVOther clinic referral/unknown January 2010-March 2011

11. Advances in HIV Testing Home-based testing: – Randomization of household members of HIV-infected patients to home-based or clinic based VCT – Household testing versus clinic VCT: 55.8% versus 10.9% OR: 10.4 (95% CI: 7.89-13.73; P<0.001) Community-based testing: Project Accept (HPTN 043) – Community-randomized study (32 communities) – Community-based plus clinic-based C&T versus clinic-based C&T – Community-based plus clinic-based: Mean difference in proportion tested: 40.2% (95% CI: 15.8-64.7%, P=).019 D etected four fold more HIV cases than clinic based (952 vs 265 (P=0.003)) Self testing: – Feasibility study in Malawi – Of 260 who opted for self-test, 99.2% accurate test – 100% indicated would recommend to friends and family Lugada et al. JAIDS, 2010 Sweat et al, Lancet 2011 Choko et al, CROI 2011

12. Expansion of Provider Initiated Testing (PIHCT)--Ethiopia 80 health facilities HIV Counseled 2,077,592 HIV Tested 1,762,636 HIV +ve: 44,835 (2.5%) ICAP-supported sites--Ethiopia

13. HIV Concordance/Discordance in Couples (DHS) Eyawo et al. Lancet 2010

14. Couples Versus Individual Counseling and Testing-- Tanzania 1521 women attending three ANC randomized to Couples C&T versus Individual C&T VariableCouple C&TIndividual C&T Proportion women receiving result39%71% HIV positive women Receive ARV for PMTCT Infants receive ARV for PMTCT 90% 55% 60% 22% Becker et al, AIDS Beh 2010

15. C UMULATIVE ENROLLMENT IN HIV CARE AND TREATMENT Number of patients Number of clinics 561,722 on ART 1,113,543 in care 768 clinics ICAP-Supported Programs

16. Woman (Mother), Age: ______ 0 1 2 3 4 5 _____6______ UAN: Man (Father), Age: _______ 0 1 2 3 4 5 _ 6______ UAN: 1 st child, Age: _______ 0 1 2 3 4 5 6 7__ UAN: 6 th child, Age: ______ 0 1 2 3 4 5 6 7______ UAN: 5 th child, Age: ______ 0 1 2 3 4 5 6 _7______ UAN: 3 rd child, Age: ______ 0 1 2 3 4 5 6__ 7_____ UAN: 2 nd child, Age: ______ 0 1 2 3 5 4 _6 7_ _ UAN: 7 th child, Age: ______ 0 1 2 3 4 5 6_ 7_____ UAN: 4 th child, Age: ______ 0 1 2 3 4 5 6_ 7______ UAN: 0 = Not counseled 4 = HIV Positive 1 = Counseled not Tested 5 = Pre-ART 2 = HIV-exposed infant 6 = ART 3 = HIV Negative 7 = Died Family Enrollment Form Date: ____/____/____ ART Client - Unique ART No. of the Index Client: __________________________________ Pre ART Client - Pre ART Serial No (Facility card number): ___________________________ Family Code Number: _________________________________________________________

17. HIV Care Continuum HIV Diagnosis ART Monitoring and Retention in Care ART eligible Pre-ART Monitoring, Retention and Adherence Support

18. From HIV Testing to HIV Care to ART Initiation-- Mozambique 1,506 Eligible for ART Initiation (49%) 23,430 Tested for HIV 7,005 Tested HIV positive (30%) 3,956 Enrolled HIV care < 30 days after HIV test (57%) 3,046 CD4 test <30 days after enrollment (77%) 317 Adherent to ART for 6 months (83%) 3,049 (43%) not enrolled in HIV care 910 (23%) No CD4 test drawn 1,035 (69%) did not initiate ART 65 (14%) LTFU after ART 471 Initiated ART < 90 days after CD4 test (31%) Micek et al JAIDS 2009

19. 62.6% newly diagnosed patients linked to care Highest % linkage in STI tested (84.1%) Lowest % linkage in VCT (53.5%) Kranzer Plos Med 2010 HIV Care Cascade by Testing Site

20. Eggers et al, CROI 2007

21. Median CD4 Count at Enrollment into Care, by Point of Referral ICAP-Supported Programs

22. Median CD4 count at enrollment into care, by enrollment year 242 cells/ul 306 cells/uL ICAP-Supported Programs

23. HIV Care Continuum HIV Diagnosis ART Monitoring and Retention in Care ART eligible Pre-ART Monitoring, Retention and Adherence Support

24. Retention in ART Programs Meta-analysis SSA Fox and Rosen, Trop Med Int Health 2010 36 cohorts 226,307 patients All losses except transfers Retention: 6 months: 86.1% 12 months: 80.2% 24 months: 76.8% 36 months: 72.3%

25. Interventions InterventionOutcome POC CD4 at HIV TestLinkage to care ART initiation Case ManagerLinkage to care Adherence support activities (counseling, home visits, treatment preparation, supportive supervision by RN Retention and ART adherence Cash transfer (transport)Retention Free cotrimoxazoleRetention of pre-ART patients Food packageVisit adherence Peer educatorsRetention (not adherence) SMS messagingAdherence Faal et al IAS 2010 Jani et al IAS 2010 Gardner et al JAMA 2005 Etienne et al. Trop Med Int Health 2010 Emenyonu CROI 2010 Kohler et al CROI 2011 Ivers et al. AIDS Res Therapy 2010 Chang et al, Plos One June 2010

26. ART for Prevention: A Multi-Component Strategy Expanded testing Linkage to care Initiation of ART Adherence support Positive prevention Testing Linkage Antiretroviral Treatment Adherence Positive Prevention Community Mobilization Policies and Guidelines Buy-in by PLWH Plus

27. Time for Action HIV Prevention Trial (HPTN 052) Releases New Findings Early initiation of ART leads to 96% reduction in HIV transmission according to study conducted by HIV Prevention Trials Network PIVOTAL STUDY FINDS THAT HIV MEDICATIONS ARE HIGHLY EFFECTIVE AS PROPHYLAXIS AGAINST HIV INFECTION IN MEN AND WOMEN IN AFRICA

28. Granich et al Lancet 2009; 373:48-57 ART for Prevention 95% reduction in new HIV cases in 10 years HIV Incidence reduced from 15-20,000 to 1000 per million Prevalence decreases to less than 1% by 2050 Granich et al, Lancet 2009 Annual testing by all >15 year old individuals All HIV+ individuals started on ART immediately 99% decrease in infectiousness High adherence with ART Low failure with first line ART

29. El-Sadr, Coburn, Blower Populations Demographics and Couple Serostatus

30. Change in HIV Incidence with Increasing ART Coverage in Discordant Couples

31. El-Sadr, Coburn, Blower Treatment Coverage and Infections Prevented

32. Conclusions-1 Evidence accumulating on the value of ART for prevention of HIV transmission Several challenges and opportunities impede/enable the potential of ART for prevention (and for treatment) –Expansion of HIV testing –Identification of individuals earlier in HIV disease –Optimization of HIV care cascade (from testing to linkage to ART initiation to retention and adherence) Seek, Link, Treat, Retain and Support

33. Conclusions-2 Implementation and scale-up need to be guided by evidence, prioritization, adaptation, innovation, monitoring and evaluation Need for continued research to: –Determine the feasibility and effectiveness of ART as prevention at a population level –Examine the effect(s) of combined interventions –Identify interventions to enable/maximizing every step of the HIV care cascade –Conduct modeling to guide prioritization and action at country levels

34. Thank you