The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), announced an early end to two clinical trials of adult male circumcision because an interim review of trial data revealed that medically performed circumcision significantly reduces a man's risk of acquiring HIV through heterosexual intercourse. The trial in Kisumu, Kenya, of 2,784 HIV-negative men showed a 53 percent reduction of HIV acquisition in circumcised men relative to uncircumcised men, while a trial of 4,996 HIV-negative men in Rakai, Uganda, showed that HIV acquisition was reduced by 48 percent in circumcised men.
"These findings are of great interest to public health policy makers who are developing and implementing comprehensive HIV prevention programs," says NIH Director Elias A. Zerhouni, M.D. "Male circumcision performed safely in a medical environment complements other HIV prevention strategies and could lessen the burden of HIV/AIDS, especially in countries in sub-Saharan Africa where, according to the 2006 estimates from UNAIDS, 2.8 million new infections occurred in a single year."
"Many studies have suggested that male circumcision plays a role in protecting against HIV acquisition," notes NIAID Director Anthony S. Fauci, M.D. "We now have confirmation -- from large, carefully controlled, randomized clinical trials -- showing definitively that medically performed circumcision can significantly lower the risk of adult males contracting HIV through heterosexual intercourse. While the initial benefit will be fewer HIV infections in men, ultimately adult male circumcision could lead to fewer infections in women in those areas of the world where HIV is spread primarily through heterosexual intercourse."
The findings from the African studies may have less impact on the epidemic in the United States for several reasons. In the United States, most men have been circumcised. Also, there is a lower prevalence of HIV. Moreover, most infections among men in the United States are in men who have sex with men, for whom the amount of benefit provided by circumcision is unknown. Nonetheless, the overall findings of the African studies are likely to be broadly relevant regardless of geographic location: a man at sexual risk who is uncircumcised is more likely than a man who is circumcised to become infected with HIV. Still, circumcision is only part of a broader HIV prevention strategy that includes limiting the number of sexual partners and using condoms during intercourse.
The co-principal investigators of the Kenyan trial are Robert Bailey, Ph.D., M.P.H., of the University of Illinois at Chicago, and Stephen Moses, M.D., M.P.H., University of Manitoba, Canada. In addition to NIAID support, the Kenyan trial was funded by the Canadian Institutes of Health Research and included Kenyan researchers Jeckoniah Ndinya-Achola, M.B.Ch.B., and Kawango Agot, Ph.D., M.P.H. The Ugandan trial is led by Ronald Gray, M.B.B.S., M.Sc., of Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Additional collaborators in the Ugandan trial were David Serwadda, M.Med., M.Sc., M.P.H., Nelson Sewankambo, M.B.Ch.B., M.Med.M.Sc., Stephen Watya, M.B.Ch.B., M.Med., and Godfrey Kigozi, M.B.Ch.B., M.P.H.
Both trials involved adult, HIV-negative heterosexual male volunteers assigned at random to either intervention (circumcision performed by trained medical professionals in a clinic setting) or no intervention (no circumcision). All participants were extensively counseled in HIV prevention and risk reduction techniques.
Both trials reached their enrollment targets by September 2005 and were originally designed to continue follow-up until mid-2007. However, at the regularly scheduled meeting of the NIAID Data and Safety Monitoring Board (DSMB) on December 12, 2006, reviewers assessed the interim data and deemed medically performed circumcision safe and effective in reducing HIV acquisition in both trials. They therefore recommended the two studies be halted early. All men who were randomized into the non-intervention arms will now be offered circumcision.
"It is critical to emphasize that these clinical trials demonstrated that medical circumcision is safe and effective when the procedure is performed by medically trained professionals and when patients receive appropriate care during the healing period following surgery," notes Dr. Fauci.
Researchers have noted significant variations in HIV prevalence that seemed, at least in certain African and Asian countries, to be associated with levels of male circumcision in the community. In areas where circumcision is common, HIV prevalence tends to be lower; conversely, areas of higher HIV prevalence overlapped with regions where male circumcision is not commonly practiced.
Results of the first randomized clinical trial assessing the protective value of male circumcision against HIV infection, conducted by a team of French and South African researchers in South Africa, were reported in 2005. That trial of more than 3,000 HIV-negative men showed that circumcision reduced the risk of acquiring HIV by 60 percent. The trial was funded by the French Agence Nationale de Recherches sur le Sida (ANRS) (see www.anrs.fr/).
For more information on the Kenyan and Ugandan trials of adult male circumcision, see the NIAID Questions and Answers document at www3.niaid.nih.gov/news/QA/AMC12_QA.htm.
The World Health Organization (WHO) press statement in response to the NIAID DSMB recommendation is available on the WHO web site, www.who.int/hiv.