Have WHO and UNAIDS gotten the wrong message from studies of circumcision to reduce men’s risk for HIV?
16 April 2012
In 2003-06, a study team funded by the US National Institutes of Health (NIH) recruited HIV-negative intact (uncircumcised) men in Rakai, Uganda, circumcised some, and then followed and retested both circumcised and intact men to see who got HIV.[1] The most widely reported data from this study say that men in the intervention (circumcised) group got HIV at the rate of 0.66% per year vs. 1.33% per year for men in the control (intact) group. These data have been used to motivate efforts to circumcise 20 million African adults by 2015 as well as to introduce routine infant circumcision.
Circumcise vs. wait and wipe
However, other data from the same study show a more effective, less dangerous, less culturally intrusive, and less expensive option for intact men to protect themselves from HIV after sexual contact – simply waiting at least 10 minutes after coitus before doing anything to clean one’s penis, and then just wiping it with a dry cloth, without water (Table). (Condom use reliably protects men from acquiring HIV from sexual partners; this note discusses waiting and wiping as an alternative to circumcision, not as an alternative to condom use.)
While all intact men in the NIH-funded Rakai trial got HIV at the rate of 1.33% per year, HIV infections in intact men concentrated in men who cleaned their penises within 3 minutes after coitus (2.32% per year) and men who used water alone to do so at any time after coitus (2.26% per year). On the other hand, intact men who cleaned their penises after coitus but waited at least 10 minutes to do so got HIV at the rate of 0.39% per year. Intact men who cleaned their penises after coitus by wiping with a dry cloth (within 3 minutes or later) got HIV at the rate of 0.55% per year. Notably, intact men who waited at least 10 minutes to clean and/or cleaned with a dry cloth were at less risk for HIV than circumcised men; and intact men who waited at least 10 minutes to clean were even at less risk than men who reported no sex partners (see Table).
According to Ronald Gray, the head of the Rakai study team, one message from the study is “there ought to be a little time left for postcoital cuddling before you go and wash. Don’t just finish and jump out of bed.”[5]
Why did intact men who cleaned later without water have lower risk for HIV?
Frederick Makumbi and other members of the Rakai study team, as well as other AIDS experts, speculated that washing could remove enzymes in vaginal fluid that neutralize HIV, that “the acidity of vaginal secretions may impair the ability of the AIDS virus to survive,” and that water with its neutral pH may facilitate viral survival.[5,6]
The study team did not consider that men’s prepuce and its secretions as well as semen – like women’s sexual organs and secretions – might also have viral defenses that are damaged by washing immediately after coitus. Years before the Rakai circumcision trial, Fleiss and colleagues’ 1998 review of the “hygienic and immunological properties of the prepuce and intact penis” noted commensal bacteria and secretions with anti-bacterial and anti-viral activity associated with the foreskin.[7]
Another possibility is that reported post-coital cleaning had little or no impact on HIV risk but was linked to other behaviors that accounted for a lot of the infections. Sixteen of the 67 incident infections recorded during the NIH-funded Rakai trial occurred in men who reported no sex partners (6 infections) or 100% condom use (10 infections),[1] which suggests that many infections came from blood exposures.[8] If men who were most worried about HIV from sex both washed immediately after sex and went for injections for (suspected) sexual infections, their greater risk for HIV may have been from unsafe injections rather than sex.
Table: Selected behaviors associated with HIV incidence among men in Rakai, Uganda
* Adjusted for condom use, marital status, age, non-marital partnerships, alcohol use with sex, perceived partners’ HIV status, sexual frequency, number of sexual partners.
† Adjusted for age, occupation, marital status, non-marital relationships, number of sexual partnerships, condom use, alcohol use, genital ulcer disease, urethral discharge, dysuria, circumcised, baseline syphilis, HSV-2.
Sources: Results for all men in the NIH-funded trial are from Gray and colleagues[1]; results for penis washing among intact men are from Makumbi and colleagues[2,3]; combined results from NIH- and Gates-funded trials are from Tobian and colleages.[4]
Other studies of penis cleaning vs. HIV
At least four studies of risks for prevalent HIV infection in Africa have reported various data on intact men’s penile hygiene vs. HIV infection. In a 1999 survey in South Africa, intact men who reported washing their penis less than once a day were 2.7 times more likely to be HIV-positive compared to men who washed at least once a day.[9] Another study in South Africa among intact men attending a sexually transmitted infections clinic reported that men with “subpreputial penile wetness” were 2.3 times more likely to be HIV-positive compared to men without wetness; wetness was in turn less common among men who reported washing after sex (with no information on time between coitus and washing).[10]
In a case control study among intact men recruited for the 2002-06 trial of circumcision to protect men in Kisumu, Kenya, men who reported “wash[ing] genitals immediately after last sexual intercourse” (without specifying the number of minutes between coitus and washing) were 0.2 times as likely to be HIV-positive as men who reported not doing so.[11] A 1999 survey in Kenya found that intact men without “adequate” genital hygiene were 1.3 times more likely to be HIV-positive compared to intact men with “adequate” hygiene (men reporting fully retracting their foreskins when washing and with no smegma on the glans penis during examination).[12]
None of these studies reported information on the timing of post-coital cleaning or on wiping vs. washing. Furthermore, in studies of risks for HIV prevalence, reverse causation could explain some of the findings; eg, men with HIV and weakened immune symptoms are more likely to get genital infections causing subpreputial wetness.
Did post-coital penile cleaning influence HIV incidence among intact men in the South African and Kenyan studies of male circumcision to protect men?
Two other trials of circumcision to protect men – in Orange Farm, South Africa, 2002-05, and in Kisumu, Kenya, 2002-06 – reported that HIV incidence in intact men was more than double HIV incidence in circumcised men.[13,14] The study team for the South African trial has not reported post-coital cleaning practices for intact men. In 2010, the study team for the Kisumu trial reported that 21% of men in the control (intact) group “washed” their penis within one hour after coitus; but the study team has not reported if or how penile cleaning was related to HIV incidence.[15] Neither team has said what information they collected about post-coital cleaning (and have not reported). The study teams have also not reported what if any advice they gave to intact men about post-coital cleansing.
Has post-coital cleaning contributed to high HIV incidence among intact men in later and continuing studies?
Post-trial studies in Orange Farm, South Africa, and in Rakai, Uganda, reported higher rates of HIV incidence in intact men compared to rates observed during the trial. In Orange Farm, a cross-sectional survey in 2007-08 reported a rate of HIV incidence in intact men of 5.6% per year (using the BED assay to identify incident infections).[16] A follow-up study in Rakai among men in the two (NIH- and Gates-funded) circumcision trials found that men who remained intact after the trials acquired HIV over the following two years at the rate of 1.93% per year compared to 1.14% per year during the trial.[17] Neither of these studies reported any information about post-coital cleansing. Similarly, neither has reported what if any advice the study team gave to intact men on when and how to clean their penises after coitus.
Some other recent studies in Africa have reported HIV incidence in intact vs. circumcised men but without any information about post-coital cleaning practices. For example, a study of HIV transmission among discordant couples with or without anti-retroviral therapy[18] asked about circumcision but not post-coital cleaning (in this reference,[19] click on “agree,” then on “individual CRFs: international sites,” then on “partner circumcision assessment” and “partner sexual history assessment”).
Recommendations
Data from Rakai, Uganda, discussed in this note have multiple implications for HIV prevention and research in Africa.
First, all interested parties should mobilize all available channels (newspapers, NGOs, churches, etc) to get two public messages to intact African men:
(a) Don’t go for circumcision. If a partner is HIV infected, you are safe with condoms. If for some reason you are exposed, according to available evidence you are safer if you are intact and wait at least 10 minutes to clean your penis than if you have been circumcised.
(b) Wait at least 10 minutes after coitus to clean your penis, and then do so by wiping with a cloth, without water or other fluid.
Second, programs to circumcise men and babies in Africa should be suspended pending further evidence on the impact of post-coital penile cleaning on HIV incidence.
Third, researchers should urgently report and/or collect and report information on HIV incidence among intact men according to post-coital cleaning practices. All relevant collected but unreported information should be disclosed (including information on post-coital cleaning, incidence of sexually transmitted disease, and injections and other blood exposures). Questions about post-coital cleaning can be added to ongoing studies of risks for HIV incidence to get information within 6-12 months. Considering the urgency of this information, it would be unwise to wait for findings from a new trial, which could take years. Moreover, considering the observed high risk for HIV associated with early cleaning and cleaning with water, it is arguably not ethical to follow men without warning them to avoid such practices.
Fourth, individuals and groups that have been opposing circumcision in Africa should independently collect information on:
(a) post-coital cleaning practices in Africa and elsewhere;
(b) official advice about post-coital cleaning in Africa; and
(c) scientific evidence about the effect of various post-coital cleaning practices on the microbiological defenses of the foreskin.
These four recommendations are not intended to be complete or decisive. This is a preliminary note. Hopefully people with relevant information and expertise will help to resolve questions raised by Rakai data on post-coital cleaning and will suggest additional questions and steps.
References
1. Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomized trial. Lancet 2007; 369: 657-666.
2. Makumbi FE, Gray RH, Wawer, M, et al. Male post-coital penile cleansing and the risk of HIV-acquisition in rural Rakai district, Uganda. Fourth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, abstract WEAC1LB, Sydney, 2007. Available at: http://www.ias2007.org/pag/Abstracts.aspx?SID=55&AID=5536.
3. Collins S. IAS feedback: news drugs and prevention studies. 20 September 2007, i-Base. Available at: http://www.powershow.com/view/82522-ZjE3O/IAS_feedback_news_drugs_and_prevention_studies_African_Treatment_Advocacy_Training_flash_ppt_presentation (accessed 14 April 2012).
4. Tobian AAR, Ssempijja V, Kigozi G, et al. Incidence HIV and herpes simplex virus type 2 infection among men in Rakai, Uganda. AIDS 2009; 23: 1589-1594. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715553/pdf/nihms121760.pdf (accessed 11 May 2012).
5. Altman LK. Washing after sex may raise HIV risk. New York Times 21 August 2007. Available at: http://www.nytimes.com/2007/08/21/health/21hiv.html (accessed 10 April 2012).
6. Bainemigisha H. Washing the penis after sex may increase HIV infection. New Vision, 12 August 2007. Available at: http://www.newvision.co.ug/D/9/34/580913 (accessed 10 April 2012).
7. Fleiss PM, Hodges FM, van Howe RS. Immunological functions of the human prepuce. Sex Transm Inf 1998; 74: 364-367.
8. Gisselquist D. Points to Consider: responses to HIV/AIDS in Africa, Asia, and the Caribbean. London: Adonis & Abbey, 2008. Available at: http://sites.google.com/site/davidgisselquist/pointstoconsider (accessed 15 April 2012).
9. Auvert B, Ballard R, Campbell C, et al. HIV infection among youth in a South African mining town is associated with herpes simplex virus-2 seropositivity and sexual behavior. AIDS 2001; 15: 885-898.
10. O’Farrell N, Morison L, Moodley P, et al. Association between HIV and subpreputial penile wetness in uncircumcised men in South Africa. J Acquir Immune Defic Syndr 2006; 43: 69-77.
11. Mattson CL, Bailey RC, Agot K, et al. A nested case-control study of sexual practices and risk factors for prevalent HIV-1 infection among young men in Kisumu, Kenya. Sex Transm Dis 2007; 34: 731-736. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562680/pdf/nihms55078.pdf (accessed 15 April 2012).
12. Agot KE, Ndinya-Achola JO, Kreiss jk, et al. Risk of HIV-1 in rural Kenya. Epidemiology 2004; 15: 157-163.
13. Auvert B, Taljaard D, Lagarde E, et al. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: The ANRS 1265 trial. PLoS Med 2005; 2: e298.
14. Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial. Lancet 2007; 369: 643-56.
15. Mehta SD, Krieger JN, Agot K, et al. Circumcision and reduced risk of self-reported penile coital injuries: results from a randomized controlled trial in Kisumu, Kenya. J Urol 2010; 184:203-9. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3090633/pdf/nihms287145.pdf (accessed 15 April 2012).
16. Lissouba P, Taljaard D, Rech D, et al. Adult male circumcision as an intervention against HIV: An operational study of uptake in a South African community (ANRS 12126). BMC Infect Dis 2011; 11: 253. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192707/pdf/1471-2334-11-253.pdf (accessed 15 April 2012).
17. Gray R, Kigozi G, Kong X, et al. The effectiveness of male circumcision for HIV prevention and effects on risk behaviors in a post-trial follow up study in Rakai, Uganda. AIDS 2012; 26: 609-615.
18. Cohen M, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Eng J Med 2011; 365: 493-505.
19. Statistical Center for HIV/AIDS Research & Prevention. HPTN 052 CRFs. Available at: https://atlas.scharp.org/cpas/login/HPTN/052/agreeToTerms.view?returnUrl=%2Fcpas%2Fproject%2FHPTN%2F052%2Fbegin.view%3F (accessed 16 April 2012).