1. Male post-coital penile cleansing and the risk of HIV-acquisition in uncircumised men, Rakai district, Uganda WEAC1LB Fredrick E Makumbi, Ronald H Gray, Maria Wawer, Gertrude F Nakigozi, David Serwadda, Godfrey Kigozi, Stephen Watya, Victor Sempijja, Fred Wabwire-Mangen 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention Sydney, Australia July 25 th 2007

2. Background  The HIV/AIDS epidemic remains unabated especially in Sub-Saharan Africa  HIV prevention interventions include: –Abstinence, fidelity (be faithful) and condoms, the “ABC” strategy –Male circumcision  Three RCTs have demonstrated efficacy of male circumcision for HIV prevention in men, and this is now recommended by WHO

3. Background  There are substantial challenges to male circumcision scale up; –Safety, acceptability, and the high cost of adult surgery –Ethical, social, cultural and human rights issues –Many national governments have not fully endorsed it  Thus, additional prevention methods need to be explored, including potential alternatives to male circumcision. These include: –Penile microbicide wipe –Post-coital cleansing with water and soap Both may reduce or eliminate potentially infectious vaginal secretions from the subpreputial space of uncircumcised men Both may reduce or eliminate potentially infectious vaginal secretions from the subpreputial space of uncircumcised men

4. Background  Use of water with/without soap following coitus is quite common in Africa  No prospective studies have assessed the impact of this practice on HIV-acquisition in uncircumcised men  Use of water and soap for STI prophylaxis have shown reductions in GUD (O'Farrell N, Genitourin Med.1993;69:297-300; Moore JE. Journal of Urology, 1920, 4: 169–176.)  Bathing after sex was associated with reduced odds of being HIV+ among largely circumcised men (Meier S. A et al, J Acquir Immune Defic Syndr & Volume 43, Number 1, September 2006) (Meier S. A et al, J Acquir Immune Defic Syndr & Volume 43, Number 1, September 2006)  Conversely, vaginal cleansing using water or soap was associated with increased HIV-acquisition among females (McClelland S.R et al, AIDS 2006, 20:269–273) (McClelland S.R et al, AIDS 2006, 20:269–273)

5. Objective  To assess the association between post- coital penile cleansing and the risk of HIV-acquisition among uncircumcised men

6. Methods

7. Methods-1  2522 uncircumcised men randomized and enrolled into the control arm of the Rakai male circumcision trial  Aged 15–49 years, HIV-negative at enrolment and accepted VCT  Follow-up visits at 6, 12 and 24 months  Data collected included socio-demographic characteristics, sexual risk behaviors, genital hygiene, and health. Biological samples for HIV and STI testing  The trial was unblinded early on December 12, 2006 because interim analysis showed a 51% efficacy

8. Methods-2  Data obtained on genital hygiene practices after intercourse included questions on; –Reported penile cleansing after sexual intercourse –Cleansing materials used  Cloth-alone, washing-alone or both –Duration of time from completion of coitus to cleansing  Self-reported times in minutes for each partner

9. Methods-3 Definitions  “washed with all partners” if the man reported cleansing the penis following coitus with all sexual partners  “washed with some partners” if he cleansed the penis with some but not all sexual partners  “never washed” if he did not report cleansing with any sexual partners  Mean duration of time to cleansing following coitus –within 3 minutes, >3-10 minutes and >10 minutes

10. Methods-4  At each follow-up visit (6, 12 and 24 months), participants were asked about behaviors preceding the interview –Prior six months preceding the 6 and 12 months FUP visits –Prior 12 months preceding the 24 month FUP visit  A total of 4,378 intervals with data on post-coital cleansing were accrued from sexually active men  In 3, 633 (83%) follow up intervals men reported they “washed with all partners”  2,356 intervals have data available on cleansing materials used

11. Statistical Analysis

12. Statistical Analysis-1  HIV incidence rate per 100 person-years (py)  Unadjusted and adjusted incidence rate ratios (IRR), 95% CI with Huber–White sandwich robust estimator using Poisson regression model  Fixed covariates were –Enrolment characteristics (age and marital status)  Time-varying covariates were –Sexual risk behaviors (consistent, inconsistent or non use of condoms, non-marital partnerships, alcohol use before sex, sex frequency, and perceived female partner’s HIV serostatus)

13. Statistical Analysis-2  Covariates in adjusted model were; –Significant at P < 0.15 in the univariate analyses –Or, unadjusted IRR>2.0 or 2.0 or <0.5 –Or, suspected confounders  Statistical significance was determined by the Wald test or the log likelihood ratio test or the log likelihood ratio test  STATA version 9.2

14. Results

15. Results -1 Follow-up intervals Incident cases/py Incidence per 100py Adjusted* IRR (95%CI) Post coital washing with partners Overall 4,37842/2629.31.60 Never washed with any partner 5674/326.71.22 1.0 Washed with some partners 1781/111.50.90 0.47 (0.05 4.67) Washed with all partners 3,63337/2191.11.69 1.20 (0.42 3.38) Adjusted IRR of HIV incidence by post-coital cleansing * Adjusted for Condom use, marital status, age, non-marital partnerships, alcohol use with sex, perceived partners’ HIV status, sex freq, number of sexual partners Consistent Washing was not associated with a reduction HIV-incidence

16. Results -2 Adjusted IRR of HIV incidence by duration from sex to penile washing among men who reported washing with all partners Chi-sq for trend=7.14, p=0.0076 HIV-incidence was significantly lower if washing was delayed > 10 minutes after sexual intercourse Follow-up intervals Incident cases/py Incidence per 100py Adjusted IRR * (95%CI) Duration from sex to penile washing (in minutes) Overall 3,63237/2190.61.69 0-3 1,78725/1078.62.32 1.0 >3-10 98410/596.01.68 0.62 (0.29 1.31) >10 8612/515.90.39 0.13 (0.03 0.54)

17. Results -3 Adjusted IRR of HIV incidence by post-coital penile cleansing methods Chi-sq for trend=3.62, p=0.0554 Increasing degree of wetness ( as assessed by self-reported washing ) was associated with a borderline significant trend of increasing risk of HIV-acquisition Follow-up intervals Incident cases/py Incidence per 100py Adjusted IRR * (95%CI) Methods used for post-coital cleansing Overall 2,32424/1566.41.53 Cloth-alone2931/182.40.55 1.0 Cloth + washing 9577/676.31.04 1.7 (0.20 4.55) Washing-alone 1,07416/707.72.26 3.7 (0.48 29.07)

18. Summary Post-coital penile cleansing is common in this population Post-coital penile cleansing, as practiced in the rural population of Rakai, does not afford protection from male HIV acquisition among uncircumcised men Washing less than 10 minutes after intercourse may increase HIV risk, relative to delayed cleansing Washing-alone is associated with a non-significant increase in HIV-incidence among uncircumcised men

19. Possible explanations Acid pH of vaginal secretions Postulated that the acid pH of vaginal secretions may impair HIV survival Use of water with a neutral pH, may facilitate viral survival and possible infectivity Delayed cleansing may reduce viral infectivity by prolonged exposure to acidic vaginal secretions

20. Limitations Observational findings in the uncircumcised control arm men Self-reported information on post-coital practices may be unreliable No direct information on use of soaps, which may potentially irritate the subpreputial mucosa. In separate interviews ~75% of men reporting washing used soap No detailed information on how the actual practice of cleansing was done

21. Recommendation Need for more epidemiologic and clinical studies to assess Viral survival in vaginal or subpreputial secretions Effects of water or other cleansing materials such as soap on HIV virus survival Subpreputial Immunological response with diluted and undiluted vaginal secretions

22. Acknowledgements Study participants in the Rakai male circumcision Trial Management and Staff of Rakai Health Sciences program Grant for the Male circumcision trial from National Institutes of Allergy and Infectious Disease (NIAID), Division of AIDS, National Institutes of Health (NIH), and in part by the Division of Intramural Research, NIAID, NIH The study was supported by a grant (UO1 AI11171-01-02)

23. Thank you