1. Male Circumcision and HIV prevention, the Evidence and potential Impact on HIV incidence in Zimbabwe Karin Hatzold, MD, MPH Director HIV Services PSI Zimbabwe Update on Sexually Transmitted Infections Harare, 29 th of September 2009

2. Overview Evidence MC for HIV prevention Evidence other benefits of MC Acceptability Risks and risk compensation MC and implications for women Population - level impact Cost-effectiveness Update on Zimbabwe MC program

3. Global Prevalence of Male Circumcision 665 million men or 30 % of the world’s male population are circumcised –68% Muslims –0.8% Jewish –13% US males

4. Male circumcision and HIV infection Bongaarts, AIDS 1989

5. HIV and MC Prevalence – Africa MC Prevalence < 20% MC Prevalence > 80% Adapted from Halperin & Bailey, Lancet 1999; 354: 1813 -1815

6. Meta-analysis of prospective studies Weiss et al AIDS. 14(15):2361-2370, October 20, 2000. Review of 27 observational studies from SSA 21 showed reduced risk of HIV among circumcised men Overall –Adjusted OR: 0.42 (95% CI: 0.34 to 0.54) Population-based studies –Adjusted* OR: 0.57 (95% CI: 0.47 to 0.70) High risk groups –Adjusted* OR: 0.31 (95% CI: 0.23 to 0.42) *Including additional studies not included in published meta-analysis

7. McCoombe & Short, AIDS 2006 20:1491-1495 How the foreskin increases risk of infection Thinly keratinized mucosal layer of inner foreskin - susceptible to minor trauma and abrasion - can facilitate entry of pathogens Area under foreskin is warm, moist environment, suitable for pathogen replication

8. How the foreskin increases risk of HIV acquisition Increased risk of genital ulcers in uncircumcised men  Increased risk of HIV through disrupted mucosal surface of the ulcer High density of HIV-1 target cells (Langerhans cells) in penis, and those in the inner foreskin are nearer the epithelial surface due to lack of keratin McCoombe, AIDS, 2006 20 p. 1491 Study of foreskin & cervical biopsies showed that inner foreskin is more easily infected with HIV than external foreskin, or cervical tissue Patterson Am J Pathol, 2002. 161 p. 867

9. Evidence for HIV risk reduction among circumcised men: 3 RCTs Orange Farm South Africa Rakai Uganda Kisumu Kenya PopulationSemi-urbanRuralUrban Male circumcision prevalence in population 20%16%10% HIV incidence1.6%1.0%1.6% Age range of study participants18-24 yrs15-49 yrs18-24 yrs Sample size3,1284,9962,784 Protective effect (ITT)60%51%53% Protective effect (as treated)76%55%60% Original source of slide (modified): Willard Cates/FHI 3 randomized controlled trials comparing new HIV infections in men who were circumcised as part of the trial and men who were not circumcised

10. Evidence for HIV risk reduction among circumcised men, Kenya Study – Further Follow-up M6M12M18M24M30M36M42Total Circumcised HIV731821224 At risk1337131312721233724532277 Uncircumcised HIV121791076465 At risk1356132012651208694476245 Bailey et al, International AIDS Conference Mexico, Aug 2008, LB HIV Incidence: Circumcised men 2.6% Uncircumcised men 7.4% Relative Risk: 0.36 (0.23, 0.57)

11. Substantially reduced risk of syphilis among circumcised men (RR = 0.67, 95%, CI: 0.54 to 0.83) Circumcised men at lower risk of chancroid (RRs: 0.12 to 1.11) 6 out of 7 studies Borderline statistical significance for reduced risk of HSV-2 infection (RR = 0.88, CI : 0.77 to 1.01) in circumcised men Male circumcision and risk of syphilis, chancroid, and genital herpes, Meta Analysis Weiss et al: Sex Transm Infect 2006;82:101–110.

12. Effect of circumcision on gonorrhea, trichomoniasis, and human papilloma virus (HPV), sub-study RCT Orange Farm Prevalence of high-risk HPV subtypes (new infections) after 21 months follow-up: –Control group24.8% –Intervention group15.8% –Prevalence ratio0.57, CI: 0.43 – 0.75) P < 0.001 MC provides no protection against gonorrhea and borderline statistical significant protection against trichomoniasis Taljaard, International AIDS Conference Mexico, Aug08, LB

13. Acceptability of Male Circumcision for Prevention of HIV/AIDS in Sub-Saharan Africa 2006: review of 13 acceptability studies in 9 sub-Saharan countries: Uncircumcised men for themselves: 65% (29-87%) Women (for their partners): 69% (47-79%) Men for their son: 71% (50-90%) Women for their son: 81% (70-90%) Westercamp, Bailey; AIDS Behav (2007) 11:341–355

14. Acceptability of Male Circumcision for Prevention of HIV/AIDS in Sub-Saharan Africa Main barriers to acceptability were costs, fear of pain, safety concerns Main facilitators of acceptability were hygiene, perceived lower risks of STIs and other health benefits Culture and ethnicity are not major barriers to the acceptability Westercamp, Bailey; AIDS Behav (2007) 11:341–355

15. Adverse effects following MC Type of ComplicationOrange Farm, South Africa Kisumu, Kenya Pain13 (0.82%) Swelling or hematoma10 (63%) Excessive bleeding9 (0.57%)4 (0.8%) Problems with appearance9 (0.57%) Other5 (0.32%) Damage to penis4 (0.25%) Insufficient skin removed4(0.25%) Infection3 (0.19%)7 (1.3%) Delayed wound healing2 (0.13%)4 (0.8%) Anesthetic complications1 (0.07%) Excessive swelling1 (0.2%) Erectile dysfunction1 (0.2%) TOTA L60 (3.8%)17 (3.5%) Source: Auvert et al, 2005 ( South Africa, Krieger et al., 2005, Kenya)

16. Behavior Change after male circumcision Rakai : No differences in sexual behavior during the trial by circumcision status Orange Farm: Increased mean number of sexual acts between 4 and 21 months among men in the circumcision arm, No increase in the number of sexual partners or change in condom use Kisumu: Decline in reported risk taking behavior during 24 months follow-up in both arms At 24 months significantly fewer men in control arm reported unprotected sex ( 46% versus 51%), Control arm reported more likely consistent condom use (41% versus 36%), and practising abstinence at 24 months ( 18% versus 14%) Source: Weiss et al, AIDS 2008, 22: 567 -574

17. Benefits for women Indirect benefits through reduction in HIV incidence among men who are circumcised Lower risk of chancroid and syphilis infection Lower risk of HPV infection and cervical cancer Lower risk of bacterial vaginosis Other indirect benefits through better opportunities of men for SRH education

18. Potential impact of male circumcision programs on women’s health HIV acquisition Risk compensation Negotiating power and violence against women Stigma, blame and discrimination Resources and resource allocation

19. Mathematical Modeling The potential impact of male circumcision to prevent HIV transmission in Zimbabwe HIV incidence could be reduced by 25% to 35% if 50% of men are circumcised MC on its own not expected to lead to the terminal decline of the HIV epidemic in Zimbabwe Over the first 30 years circumcising men aged between 20 to 29 years could lead to a greater reduction in HIV incidence In the long-term, circumcising infants or boys (younger than 19 years of age) could lead to greater reductions in incidence; but no impact for the first 20 years Men being circumcised should be encouraged to test for HIV − but no substantial dangers of increased incidence if infected men are circumcised

20. Number of new male circumcisions required for adults and neonates, 2009-2030 Zimbabwe

21. New Infections Averted (Cumulative 2009-2025)

22. Discounted Cost per Infection Averted (2009-2025)

23. Scaling up male circumcision to reach 80 percent of adult and newborn males in Zimbabwe by 2015 would: avert almost 750,000 adult HIV infections between 2009 and 2025 yield total net savings of more than US$3.8 billion between 2009 and 2025 require more than 1.1 million MCs in the peak scale-up year (2012) Scaling up male circumcision to reach 80 percent of adult and newborn males in Zimbabwe by 2015 would: avert almost 750,000 adult HIV infections between 2009 and 2025 yield total net savings of more than US$3.8 billion between 2009 and 2025 require more than 1.1 million MCs in the peak scale-up year (2012) Key Messages

24. MC Epidemiological Data Zimbabwe HIV Prevalence of 15.6% ( 2007 Estimates) Geographic variations of MC prevalence DHS 2005-2005 National prevalence of 10.3% Distribution fairly uniform across the country exception of Matabeleleand North 18.8% Mashonaland Central 5.3%

25. √ MC policy developed √ MC Communication campaign √ Learning sites: Karanda Mission Hospital, Mutare Provincial Hospital (PPP), Stand-Alone site Bulawayo ( PSI managed), Manyame Airbase √ Established national training site (ZNFPC) and training program, TOT approach with cascade training √ National Training guidelines, MC kit and supplies system, M&E tools √ Referral system between HIV Testing and Counseling service providers and MC program √ Circumcised 1000 males at two sites since May 09 Zimbabwe’s MC program

26. Thank You