1. Washington D.C., USA, 22-27 July 2012www.aids2012.org Implementation Science: Realizing the HIV Prevention Revolution Nelly R. Mugo, MD, MBChB, MMed, Kenyatta National Hospital/ University of Nairobi. University of Washington

2. Washington D.C., USA, 22-27 July 2012www.aids2012.org 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 6 th most common globally

3. Washington D.C., USA, 22-27 July 2012www.aids2012.org 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org Roadmap for the prevention revolution Think populations for targeted interventions Prioritize interventions that work Deliver in combination and with high coverage

6. Washington D.C., USA, 22-27 July 2012www.aids2012.org 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org Marginalized populations require 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org High risk in young women: Kenya 65% of new infections among women occur before age 35 years The same pattern holds true of South and East African countries Kenya AIDS Indicator Survey 2007

11. Washington D.C., USA, 22-27 July 2012www.aids2012.org Thinking population Prioritize activities –Specific to priority population –Address vulnerabilities –Deliver comprehensive packages designed for populations *Jewkes Lancet 2010

12. Washington D.C., USA, 22-27 July 2012www.aids2012.org Roadmap for the prevention revolution Think populations for targeted interventions Prioritize interventions that work Deliver in combination and with high coverage

13. Washington D.C., USA, 22-27 July 2012www.aids2012.org 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org Total HIV-1 Transmission Events: 39 HPTN 052: randomized clinical trial of immediate vs delayed ART in couples Linked Transmissions: 28 Unlinked or TBD Transmissions: 11 p < 0.001 Immediate ART: 1 Delayed ART: 27 One infection in immediate arm was soon after HAART 96% reduction in HIV transmission Cohen et al NEJM 2011.

15. Washington D.C., USA, 22-27 July 2012www.aids2012.org ART only works when taken Cohen et al NEJM 2011. Immediate Arm Delayed Arm (not on ART) Delayed Arm (on ART) In HPTN 052, viral suppression was near-universal, reflecting intensive strategies, including quarterly monitoring and individual counseling, to achieve near-perfect adherence

16. Washington D.C., USA, 22-27 July 2012www.aids2012.org Pivotal randomized, placebo-controlled trials of PrEP for HIV prevention iPrExTDF 2 Partners PrEP Population Men who have sex with men Heterosexual men and women Heterosexual HIV serodiscordant couples Location US, Brazil, Ecuador, Peru, South Africa, Thailand BotswanaKenya, Uganda Sample size249912194758 InterventionDaily oral FTC/TDF HIV protection due to PrEP (FTC/TDF) 44% (95% CI 15-63%) 62% (95% CI 22-83) 75% (95% CI 55-87%) 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org PrEP (like ART) works when taken % of blood samples with tenofovir detected HIV protection efficacy in randomized comparison Partners PrEP FTC/TDF arm 81%75% TDF279%62% iPrEx51%44% FEM-PrEP26%6% 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org Risk perception: Behaviour matters 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org PrEP is 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org USA FDA reviewed and approved a label indication for emtricitabine/tenofovir (Truvada®) for HIV prevention on July 16 th 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org It was said that ART could not be done “…. In Africa, a higher proportion of patients are likely to fall into the category of potential poor adherers unless resource intensive adherence programmes are 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org Behavioural Intervention HIV Counselling and Testing Coates T, Lancet 2000 Structural / legal Male & female condoms Treatment of STIs Grosskurth H, Lancet 2000 Male circumcision Auvert B, PloS Med 2005 Gray R, Lancet 2007 Bailey R, Lancet 2007 Treatment for prevention Donnell D, Lancet 2010 Cohen M, NEJM 2011 Microbicides for women Abdool Karim Q, Science 2010 Grant R, NEJM 2010 (MSM) Baeten J, NEJM 2012 (couples) Thigpen, NEJM, 2012 (Heterosexuals) Oral pre-exposure prophylaxis Post Exposure prophylaxis (PEP) Scheckter M, 2002 HIV PREVENTION combined interventions

23. Washington D.C., USA, 22-27 July 2012www.aids2012.org Long-lasting protection from VMMC ‘a cut with extended benefit’ (Last trial visit ) 102030 40months % HIV Incidence 0 Uncircumcised Circumcised 68% Effectiveness – Extending long after RCT Results from extended Rakai study (from Kong et al, CROI, 2011) Similar results from Kenya and South Africa trial sites, no evidence of risk compensation

24. Washington D.C., USA, 22-27 July 2012www.aids2012.org 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org Roadmap for the prevention revolution Think populations for targeted interventions Prioritize interventions that work Deliver in combination and with high coverage

26. Washington D.C., USA, 22-27 July 2012www.aids2012.org 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org Synergies– HIV prevention is a team effort: Cambodia 1.0100%CUP STI case management IEC/BCC Health Workers Local Authority Police brothel owners Sex workers Special campaigns (Posters, leaflets, bill boards…) Media (TV, radio, News paper) STD Clinic HC Advocacy Monitoring RH/NGO Mean Chhi Vun, AIDS 2012 www.nchads.org For high coverage, Cambodia has a framework that includes both social and medical care services to reach MSMs

28. Washington D.C., USA, 22-27 July 2012www.aids2012.org Navneet Garg | Global Business Manager | Vestergaard Frandsen In Kenya: 41,040 people tested in 1 week during a community outreach 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

29. Washington D.C., USA, 22-27 July 2012www.aids2012.org Delivery of highly effective prevention interventions will not be without challenges

30. Washington D.C., USA, 22-27 July 2012www.aids2012.org We need high testing coverage linkage to care viral suppression to reduce infectiousness and HIV incidence at population levels The leaky cascade

31. Washington D.C., USA, 22-27 July 2012www.aids2012.org 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org We have little experience with starting ART in asymptomatic persons… Heffron et al JAIDS 2012 CROI 2012 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

33. Washington D.C., USA, 22-27 July 2012www.aids2012.org Patient empowerment improves retention in care N ( 4177)% Deaths1313.1% LTFU40.1% Remaining in care 404296.8% Improving testing & linkage to care

34. Washington D.C., USA, 22-27 July 2012www.aids2012.org Improving testing & linkage to care 100% Strategies that have worked – Home based HIV testing – Point of Care CD4 count – Community delivery of ART *Barnabas TasP 2012

35. Washington D.C., USA, 22-27 July 2012www.aids2012.org Parallel challenges, parallel opportunities ART for HIV preventionPrEP for HIV prevention AdherenceNecessary for efficacy Sexual risk-taking Principal question is whether risk-taking would be sufficient to undermine prevention benefits Antiretroviral resistance Established risk, associated with poor adherence, rising in Africa In trials, only with use in acute infection. Must be weighed against infections averted. Who will use? In theory, all HIV+s. Life-long. Target to those at highest risk. Season of highest risk. Who will pay? Rising need = rising costs Where to fit in the priority list?

36. Washington D.C., USA, 22-27 July 2012www.aids2012.org Demonstration project approach – ART with PrEP as a bridge in couples ART and PrEP work together to drive down HIV risk

37. Washington D.C., USA, 22-27 July 2012www.aids2012.org Roll-out of male circumcision: substantial country differences % of target achieved

38. Washington D.C., USA, 22-27 July 2012www.aids2012.org 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 Kawango Agot

39. Washington D.C., USA, 22-27 July 2012www.aids2012.org ARVs have made elimination of mother to child HIV transmission a feasible goal Source: Mahy, Stover, Kiragu et al, Sex Transm Infect 2010 86: ii48-ii55, 2011 This has required combination of biomedical and behavioural interventions

40. Washington D.C., USA, 22-27 July 2012www.aids2012.org 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org 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. Washington D.C., USA, 22-27 July 2012www.aids2012.org Acknowledgement IAS Conference organizers Kenyatta National Hospital All investigators, advocates, sponsors and seekers of new HIV prevention tools Kenya Prevention Revolution team Nduku Kilonzo: Kenya LVCT, Peter Cherutich: Kenya NASCOP Jared Baeten, Connie Celum: University of Washington All of you for listening THANK YOU, ASANTE SANA