In recent years, the male foreskin—a double-folded tube of skin and mucous membrane that covers the head of the penis—has taken center stage in the battle against HIV. The foreskin is rich in Langerhans cells, immune cells that are particularly easy for the virus to access. Following infection, these cells not only serve as reservoirs for replicating the virus, but also transport it to nearby lymph nodes where HIV spreads to other immune cells. Studies have shown that removal of the foreskin can reduce a man’s risk of heterosexually acquired HIV infection by 50 to 65 percent, findings that prompted large-scale circumcision campaigns in countries with high infection rates, such as sub-Saharan Africa, where heterosexual sex is primarily responsible for the HIV epidemic. Studies had also suggested that circumcision could reduce the rate of male-to-female transmission of the virus, but that turns out not to be the case.

A Ugandan study, led by Dr. Maria J. Wawer of Johns Hopkins Bloomberg School of Public Health in Baltimore, was stopped early after it became apparent that male circumcision offered no protection to female partners. The study involved 922 uncircumcised, HIV-infected men between 15 and 49 years of age who were randomly chosen to either be circumcised or remain uncircumcised. The HIV-free female partners of the male participants were also enrolled in the study, 90 in the circumcised group and 70 in the uncircumcised group, and their HIV status was evaluated after 6, 12 and 24 months. All participants were intensively schooled in HIV prevention and provided free condoms.

After two years, 18 percent of the women in the circumcised group had become infected with HIV, compared with 12 percent in the uncircumcised group. Cumulative probability of HIV infection at 24 months was 22 percent among women in the circumcised group and 13 percent among those in the uncircumcised group. The majority of the infections in the circumcised group occurred within the six months following the procedure. The researchers said the infections were caused because some of the men had intercourse before their circumcision wounds had healed, exposing their female partners to HIV-infected blood in the vagina.

The researchers said though they were disappointed with the outcome of the study, circumcision campaigns are still valid. “The efficacy of male circumcision for prevention of HIV in uninfected men is clear, and reductions in male acquisition of HIV attributable to circumcision are likely to reduce women’s exposure to HIV-infected men. Male circumcision programs are thus likely to confer an overall benefit to women,” the researchers concluded.

In an editorial accompanying the study, Dr Jared M. Baeton, from the University of Washington in Seattle, and colleagues stressed the importance of circumcision programs for men at risk of HIV, and argued for more effort being focused on people in relationships where one partner is HIV-infected and the other is not. “Prevention services for this population, including HIV testing for couples, facilitated disclosure of HIV seropositivity, and ongoing counseling services, should be a public health priority,” they write. “Such services should be incorporated into male circumcision programs, thereby providing further protection to HIV uninfected women.”

An estimated 33 million people worldwide are living with HIV/AIDS, but the World Health Organization (WHO) says circumcision has the potential to dramatically reduce the toll of the virus, averting an estimated 5.7 million new infections and three million deaths over the next 20 years in sub-Saharan Africa alone.

Both the study and the editorial appear in the July 18 issue of The Lancet.

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