HARVARD UNIVERSITY SCHOOL OF PUBLIC HEALTH

1. HARVARD UNIVERSITY SCHOOL OF PUBLIC HEALTH New Directions and Shifting Priorities in HIV Prevention (& some “Big Picture” Questions for Global Health…) Daniel Halperin, PhD Department of Global Health and Population Harvard University School of Public Health UN General Assembly, October 24, 2008

2. 40 Millions Oceania 35 Middle East & North Africa Eastern Europe & Central Asia 30 Latin America and Caribbean North America and W & C Europe Number of people living with HIV 25 Asia Sub-Saharan Africa 20 15 10 5 0 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Year Estimated number of adults and childrenliving with HIV, by region, 1990–2007

4. Estimated adult (15–49 yrs) HIV prevalence globally & in Sub-Saharan Africa, 1990–2007 8 Sub-Saharan Africa 7 6 5 Adult HIV prevalence rate (%) 4 3 Global 2 1 0 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Year

5. Heterogeneity of HIV:African Evidence • Globally, most HIV strategies look very similar, yet HIV is extraordinarily heterogeneous • HIV reached most places at similar times, but has spread very differently • Understanding heterogeneity is critical for developing more effective prevention strategies

6. Transmission Dynamics • Concentrated Epidemic - transmission occurs largely among vulnerable groups; vulnerable group interventions would reduce overall infection • Generalized Epidemic – transmission occurs primarily outside vulnerable groups and would continue despite effective vulnerable group interventions • Epidemics don’t inevitably keep escalating

7. HIV Prevalence in Asia Source: Chin, 2003

8. HIV Prevalence, Transmission Sources &HIV-AIDS Funding in Accra, Ghana Sources: NACP, GAC, CDC< MAP, 2005

9. HIV Transmission Patterns inMashonaland, Rural Zimbabwe Wilson and Cowan et al, 2003

10. Sexual Partnerships in Lesotho Sources: FHI BSS, 2002

11. Concurrent Partnerships Globally Sources: M. Carael, 1995; Halperin and Epstein, Lancet 2004

12. “Reassessing HIV Prevention” [in Generalized Epidemics] Potts M, Halperin D, Kirby D, Swidler A, Klausner J, Marseille E, Hearst N ,Wamai R, Kahn J, Walsh J. Science, May 9, 2008 “The largest investments in HIV prevention for generalized epidemics are being made into those interventions where evidence for large-scale impact is increasingly uncertain. Resources and attention need to be shifted to those approaches where the evidence of impact is greatest, namely male circumcision and decreasing multiple concurrent partnerships [and increasing access to FP].” And: Halperin D, Potts M, Kirby D, Klausner J, Wamai R, Swidler A, Marseille E, Walsh, J, Hearst N. (Response letter), Science, September 19, 2008

13. Successes & Failures of HIV Prevention in Africa • Epidemiological background (Why is HIV so high in Africa?): • The difference between concentrated and generalized epidemics • Pervasive multiple (especially concurrent) partnerships/networks • Lack of male circumcision • Weak (or even negative) evidence for the “standard” HIV prevention approaches: • “ABC” (mainly condom distribution/promotion and, more recently, abstinence-based programs for youth) • HIV testing and counseling • Treatment of other sexually transmitted infections (etc.)… • Thus new approaches -- and *priorities* -- needed for HIV prevention

14. Concurrent Partnerships Globally Sources: M. Carael, 1995; Halperin and Epstein, Lancet 2004

15. “Acute Infection” and Concurrence

16. Sexual Networking in Likoma, Malawi Source: Kohler H and Helleringer S. The Structure of Sexual Networks and the Spread of HIV in Sub-Saharan Africa: Evidence from Likoma Island (Malawi). PARC Working Paper Series: WPS 06-02 • A fifth of population in exclusive dyadic relationships • Two-thirds linked by single chain of infections over last 3 years • Networks not linked by sex workers or other “high frequency transmitters” • Linked by decentralized, complex, robust chains of sexual relationships

17. Modeling Sexual Networks Mean: 1.74 Number of Partners Mean: 1.68 Mean: 1.80 Mean: 1.86 Largest components In largest component: 2% 10% 41% 64% Low degree networks create a transmission core Bicomponents in red Source: Martina Morris, University of Washington and James Moody, Duke University, Meeting on concurrent sexual partnerships and sexually transmitted infections, Princeton University, 6 May 2006.

18. HIV prevalence* by partner faithfulness (Cameroon) Source: Dr. Vinod Mishra, ORC MACRO 2006 (DHS survey 2004)

19. Just as some drugs don’t cross the blood brain barrier; we have a very difficult time getting condoms to cross the marriage and relationship barriers.

20. Behavioral & HIV Trends in Uganda: A “Social Vaccine”?? Sources: WHO/GPA surveys; Stoneburner and Low-Beer, Science, 2004

22. Male circumcision & HIV prevalence in population-based surveys (DHS) in Africa High (>80%) male circumcision Low (<20%) male circumcision *Note: very few men in Rwanda report multiple sexual partners in past year (5%), compared to other African countries. **HIV prevalence in Kisumu area, where most men are uncircumcised, is much higher than in rest of Kenya. Source:s DHS survey data

23. Male circumcision and national HIV prevalence estimates in Asia High (>80%) male circumcision Low (<20%) male circumcision Source: World Bank Report on MC and HIV Prevention (2008 )

24. HIV Prevalence by Male Circ. (Kenya) Source: DHS Kenya 2003

25. 12 African “PEPFAR Focus” Countries HIV in adults* Estimated Male Circ. %** “Higher Risk Sex” (Males)*** C at last “Hi-risk” Sex (Males)*** Botswana 25% 15% 65% 78% Namibia 21%? 20% 47% 68% South Africa 16% 35% 40%? 57% Zambia 15% 15% 29% 60% Mozambique 16%? 60% 58% 33% Tanzania 7% 70% 52% 35% Kenya 7% 80% 40% 47% Uganda 6% 25% 28% 60% Cote d’Ivoire 4% 95% 87% 50% Nigeria 3%? 95% 78% 47% Rwanda 3% 10% 12% 51% Ethiopia 1.5% 95% 21% 31% * UNAIDS 2004 estimate, and/or population-based survey estimate ** Based on DHS, SBS or other survey data, or from ethnographic research methodologies (ie, Drain et al. 2004, JAIDS) *** % of males reporting non-married, non-cohab. partner in previous year, from DHS, UNAIDS, etc. data sets (‘98-04)

26. Physician and health show host Dr Themba Ntiwani, Swaziland: "Everyone wants to have it done. Not one person has called to say it's 'un-Swazi" Source: Timberg, Wash Post, Dec. 2005

27. Acceptability of MC in Currently Non-Circumcising Communities in Africa Source: Westercamp N, Bailey RC. , AIDS Behav. , 2006

28. Botswana – MC uptake of 80% over 10 years, relative risk = 0.33 Nagelkerke et al, BMC Inf. Dis. 2007

29. Modeled Implications HIV+ 16 14 12 10 8 6 4 2 0 0 2 4 6 8 10 Year Male Circumcision No Male Circumcision Moses et al, 1992

30. Other Important Benefits of Circumcision for Male (and Female) Reproductive Health Reduction of other STIs, including chancroid & syphilis (some protection for herpes) Elimination of phimosis & balanitis (foreskin infection) Huge reduction in invasive penile cancer Significant reduction of cervical cancer among female partners Significant reduction of urinary tract infections (in infants)

31. Benefits of Adding Family Planning to PMTCT Services in 14 High Prevalence Countries Stover, Fuchs, Halperin, Gibbons, Gillespie, Paper in review (http://www.usaid.gov/our_work/global_health/pop/news/issue_briefs/familypmtct.html)

32. What About Breast Feeding & Mother-to-Child Transmission? A 1990s South Africa study suggested that Exclusive Breast Feeding (EBF) greatly reduces HIV risk to babies More recent, large studies from Zimbabwe, Zambia and Botswana confirm that EBF lowers HIV risk by at least half compared to mixed feeding (breast milk and other foods)

33. The Standard HIV Prevention Methods - • Condom Promotion: Success stories (e.g., Thailand), in concentrated epidemics driven by commercial sex work, etc. • HIV Testing and Counseling: Important as gateway to treatment/care – but little evidence of reducing risky behavior • Treatment of Other Sexually Transmitted Diseases: Also important for public health reasons, yet 8 out of 9 clinical trials found reduced STDs but no impact on HIV • Youth (including Abstinence-based) Programs: Worth promoting delay of debut, use of contraception, etc., but little likelihood of impacting on the overall HIV epidemic

34. HIV Incidence & VCT in Harare, Zimbabwe Highly acceptable VCT did not reduce HIV incidence HIV incidence was higher (almost stat. significantly) in high uptake (intensive) VCT arm Lends support to “adverse behavioral consequences in some HIV-negative clients” Corbet, E. Makamure B., et al AIDS 2007, 21:483-9

35. Early successes: Thailand and “100% condoms”

36. Early successes: Uganda and “zero grazing” Maureen Maureen

37. Behavior Change among Males in Manicaland, Zimbabwe Source: Gregson et al, 2006

38. % Reporting 2+ Partners in last 12 Months, South African National Surveys

41. The horror of Slim is forcing people to change social habits.…A number of wives openly go so far as to confess that Slim has saved their marriages…In Bugolobi, a young housewife with three children, declared with a gleam in her eye, “There has been a positive change in our marriage. My husband stays at home much more. And I encourage him to do so by enthusiastically keeping him informed of the latest gossip about Slim victims.”(New Vision, October 23, 1987, p.10) “Female-Controlled Method” of HIV Prevention?: Uganda in Late 1980s

42. The Difference between Response to AIDS in Botswana, compared to Uganda: “Aids had not gone beyond the headspace of awareness, education and counselling to a lower centre of gravity between the gut and the heart of behaviour change.“ (Daniel Low Beer, 2003)

43. Which Model for Southern Africa? Botswana: A mainly exogenous/donor-driven, top-down response that focused on commodity and clinical service provision Prioritized condom promotion to general population Supported by strong political leadership Uganda: Prioritized behavior change (particularly partnerreduction; the “B” in the “ABCs”) in the general population through a “zero-grazing” approach, involving churches, traditional leaders & healers, etc. Featured an endogenous, grassroots, locally developed, community-based response that was supported by strong political leadership.

44. “ABCs” of HIV Prevention ircumcision ontraception B C C C A

47. Monitoring Behavior Change in Swaziland: 12 sites (random sample, stratified U/R) 2120 adults (2005) and 2112 (2006) 21% repeat participants in 2006 54% female (2005) vs 64% (2006) Average age 28 years (both cycles) CIET

48. Reported Sexual Behaviour, Swaziland USAID-funded evaluation: Andersson, Salcedo, Halperin, Brown, Bicego, Mavuso

49. 2006: Exposure to Makhwapheni (“Secret Lover”) Campaign, Swaziland % who answered yes