Implementation Science: Realizing the HIV Prevention Revolution

1. Implementation Science: Realizing the HIV Prevention Revolution Nelly R. Mugo, MD, MBChB, MMed, Kenyatta National Hospital/ University of Nairobi. University of Washington

2. The HIV pandemic remains a global health challenge • From 1980s to present • Approximately 30 million deaths • 2010 HIV global estimates • 34 million people living with HIV/AIDS • 2.7 million newly infected • 1.8 million deaths • AIDS is still the commonest cause of death in Africa and 6th most common globally

3. The HIV prevention revolution • 30 years into the HIV epidemic, new research has demonstrated that we now have powerful interventions to prevent new infections • For the first time, we can begin to visualize a future free from HIV/AIDS as a feasible goal

4. Changing how we deliver HIV prevention services: road map • Think populations for targeted interventions • Prioritize interventions that work within populations • Deliver in combination and with high coverage for high impact

5. Roadmap for the prevention revolution • Think populations for targeted interventions • Prioritize interventions that work • Deliver in combination and with high coverage

6. Source of new HIV infections in generalized epidemic: the epidemic within epidemics Swaziland, Lesotho, Uganda, Malawi heterosexual unions contribute the majority of new infections

7. Heterosexual couples • The majority of new HIV-1 cases in sub-Saharan Africa occur among couples • HIV-serodiscordancy is common: 50% of partners of HIV-1 infected persons are HIV uninfected • Risk of HIV transmission in couples who do not know they are sero-discordant ~14% • Without couples counseling and testing , it may be unclear who is at risk and a target for intervention • Among sero-discordant couples desire for children overshadows fear of infection and is a risk driver

8. Marginalized populationsrequire prioritized HIV interventions • HIV prevalence is high (Data from *SWOP-Kenya) • 40% among MSM • 28% among female sex workers • And a minority correctly use condoms • Social and policy environment keep these at risk populations marginalized and reluctant to seek health services • Sodomy in Kenya is illegal with a 14 year jail sentence • Experience social condemnation, physical and sexual abuse *Sex workers project (SWOP), University of Nairobi

9. There can be no HIV revolution without youth Globally, 42% of new HIV infections are among youth age 15-24 years • 80% (4 million) of these infections are in sub-Saharan Africa • Young women, have twice the HIV infection rates as young men

10. High risk in young women: Kenya Kenya AIDS Indicator Survey 2007 • 65% of new infections among women occur before age 35 years • The same pattern holds true of South and East African countries

11. Thinking population • Prioritize activities • Specific to priority population • Address vulnerabilities • Deliver comprehensive packages designed for populations *Jewkes Lancet 2010

12. Roadmap for the prevention revolution • Think populations for targeted interventions • Prioritize interventions that work • Deliver in combination and with high coverage

13. ARVs for prevention: breakthroughs • 2011: Research provided clear and unequivocal evidence that antiretroviral treatment and PrEP work for the prevention of sexual transmission of HIV • 2012: We know the what. The question now is HOW?

14. HPTN 052: randomized clinical trial of immediate vs delayed ART in couples Total HIV-1 Transmission Events: 39 Unlinked or TBD Transmissions: 11 Linked Transmissions: 28 One infection in immediate arm was soon after HAART • 96% reduction in HIV transmission Immediate ART: 1 Delayed ART: 27 p < 0.001 Cohen et al NEJM 2011.

15. ART only works when taken In HPTN 052, viral suppression was near-universal, reflecting intensive strategies, including quarterly monitoring and individual counseling, to achieve near-perfect adherence Immediate Arm Delayed Arm (not on ART) Delayed Arm (on ART) Cohen et al NEJM 2011.

16. Pivotal randomized, placebo-controlled trials of PrEP for HIV prevention Grant et al N Engl J Med 2010 Thigpen et al N Engl J Med 2012 Baeten et al N Engl J Med 2012

17. PrEP (like ART) works when taken There is a clear dose-response between evidence of PrEP use & efficacy Baeten et al N Engl Med 2012 Grant et al N Engl J Med 2010 Van Damme et al N Engl J Med 2012 Thigpen et al N Engl J Med 2012

18. Risk perception: Behaviourmatters What motivates PrEP use? • Serodiscordant couples have a known HIV+ partner, decided to stay together, motivates high adherence • FEM-PrEP, young women • 70% perceived themselves to be at little or no HIV risk resulting in lower adherence • Yet HIV incidence was 5% per year! Risk perception is key for any strategy to be effective

19. PrEPis not lifelong, it is for a season • Adolescent women present a season of vulnerability • High HIV incidence East and Southern Africa ages 16-24 years • HIV serodiscordant couples trying to conceive • Young men who have sex with men • Couples where there is intimate partner violence, new partner, depression, alcohol & drug use and perhaps in conflict zones

20. USA FDA reviewed and approved a label indication for emtricitabine/tenofovir(Truvada®) for HIV prevention on July 16th 2012 • We now have a powerful tool, that can safely be used by populations of vulnerable HIV-negative individuals • We have been waiting decades for a tool under the control of a negative woman or man.

21. It was said that ART could not be done “…. In Africa, a higher proportionof patients are likely to fall into the category of potentialpoor adherers unless resource intensive adherence programmesare available.” Remember the critiques of ART roll-out in Africa: it was done and we can do more Antiretroviral therapy in Africa Stevens et al. BMJ  2004

22. Treatment of STIs Male circumcision Microbicides for women Grosskurth H, Lancet 2000 Auvert B, PloS Med 2005 Gray R, Lancet 2007 Bailey R, Lancet 2007 Abdool Karim Q, Science 2010 Male & female condoms Structural / legal HIV PREVENTION combined interventions HIV Counselling and Testing Oral pre-exposure prophylaxis Coates T, Lancet 2000 Grant R, NEJM 2010 (MSM) Baeten J , NEJM 2012 (couples) Thigpen, NEJM, 2012 (Heterosexuals) Behavioural Intervention Post Exposure prophylaxis (PEP) Treatment for prevention Donnell D, Lancet 2010 Cohen M, NEJM 2011 Scheckter M, 2002

23. Long-lasting protection from VMMC‘a cut with extended benefit’ Uncircumcised % HIV Incidence Similar results from Kenya and South Africa trial sites, no evidence of risk compensation 68% Effectiveness – Extending long after RCT Circumcised 0 (Last trial visit) 40 months 10 20 30 Results from extended Rakai study (from Kong et al, CROI, 2011)

24. Prioritize what works • FINALLY, we have additional tools for a package of interventions that work – we have never been here before • It is time to revisit and revise how interventions are prioritized – time to focus resources and efforts on proven and impactful interventions • We have to be ready to get rid of policies and approaches that do not work • The revolution is targeting populations and providing relevant packages

25. Roadmap for the prevention revolution • Think populations for targeted interventions • Prioritize interventions that work • Deliver in combination and with high coverage

26. Combination high impact HIV prevention • Synergies of effective interventions in combination: • Reduce HIV infectiousness (eg ART, condoms), and • Reduce HIV susceptibility (eg male circumcision, PrEP, vaccine) & behavioral interventions with • High coverage Coates, Lancet 2008

27. Synergies– HIV prevention is a team effort: Cambodia 1.0 100% CUP IEC/BCC STI case management HC Local Authority Police Health Workers RH/NGO Advocacy Monitoring brothel owners Sex workers STD Clinic Media (TV, radio, News paper) Special campaigns (Posters, leaflets, bill boards…) For high coverage, Cambodia has a framework that includes both social and medical care services to reach MSMs Mean ChhiVun, AIDS 2012 www.nchads.org

28. Testing is the gateway to HIV prevention and care • Acceptability of HIV testing is high in large scale campaigns and Home based community testing • Testing must be linked to services & not simply numbers • Requires systems for effective linkage to services In Kenya: 41,040 people tested in 1 week during a community outreach Navneet Garg | Global Business Manager | Vestergaard Frandsen

29. Delivery of highly effective prevention interventions will not be without challenges

30. The leaky cascade • We need • high testing coverage • linkage to care • viral suppression • to reduce infectiousness and HIV incidence at population levels

31. Willingness to start antiretrovirals • Soweto, South Africa:7287 adults tested for HIV 2562 (35%) HIV infected 743 (29%) eligible for ART (CD4<200***) 148 (20%) refused • Most common reason for refusal was feeling well Katz et al. AIDS 2011

32. We have little experience with starting ART in asymptomatic persons… • Among HIV+ members of discordant couples in Thika, Kenya • 42% of men and 31% of HIV infected women said they would NOT be willing to initiate ART solely to lower the chance of infecting their partner • Concerns: Fear of side effects of ART, stigma , pill burden and potential for developing resistance Heffron et al JAIDS 2012 CROI 2012

33. Improving testing & linkage to care • Patient empowerment improves retention in care

34. Improving testing & linkage to care • Strategies that have worked • Home based HIV testing • Point of Care CD4 count • Community delivery of ART 100% *Barnabas TasP 2012

35. Parallel challenges, parallel opportunities

36. Demonstration project approach – ART with PrEP as a bridge in couples ART and PrEP work together to drive down HIV risk

37. Roll-out of male circumcision: substantial country differences % of target achieved

38. Lessons learnt from VMMC implementation Kenya • The HIV prevention plan must be community owned- at all levels from government to local communities • In Kenya the Luo council of elders endorsed MMC • Educate the public through social media • For population impact: target & coverage matters • Be flexible & creative • Monitor and Evaluate to catch problems early and intervene JUST DO IT Adapted from KawangoAgot

39. ARVs have made elimination of mother to child HIV transmission a feasible goal This has required combination of biomedical and behavioural interventions Source: Mahy, Stover, Kiragu et al, Sex Transm Infect 2010 86: ii48-ii55, 2011

40. Summary • Target Population • We need to change course and target population, then apply interventions that fit the populations • Youth are key, and should be prioritized if we are to reverse the tide of this epidemic • Programs should reflect this mind shift and start with populations then provide appropriate intervention package • Proven Intervention • we finally have tools that are proven to be highly efficacious, • we must carefully select both biomedical and behavioral tools appropriate to each at risk population • Coverage • For high impact, must have high coverage, link testing to services • Reduce leakages in prevention cascade • Process of prevention needs to belong to communities www.aidsmark.org

41. Give them a future without HIV • We have a real opportunity in the history of this disease to make a remarkable difference and save lives –this is not a choice but obligation • We shall be judged on how well we utilized the knowledge we have accrued to save men and women from getting infected with HIV • Hopefully fulfilling a dream for future generations of an HIV free life

42. Acknowledgement IAS Conference organizers Kenyatta National Hospital All investigators, advocates, sponsors and seekers of new HIV prevention tools Kenya Prevention Revolution team NdukuKilonzo: Kenya LVCT, Peter Cherutich: Kenya NASCOP Jared Baeten, Connie Celum: University of Washington All of you for listening THANK YOU, ASANTE SANA