Foreskin may permit HIV entry, infection.

Circumcision seems to arm men with a degree of protection against HIV, the AIDS virus, but the mechanism underlying this defense has been unclear. A new study bolsters earlier reports implicating the foreskin of the penis as one of HIV's portals to the body. The study also finds that while circumcision confers some protection against HIV, it doesn't guard against other sexually transmitted diseases.

Robert C. Bollinger of the Johns Hopkins Medical Institutions in Baltimore and his colleagues identified 2,107 uncircumcised and 191 circumcised men attending health clinics in Pune, India, during the 1990s. Most were unmarried men in their 20s, and all were free of HIV at the outset of the study. Over 18 months, 165 of the uncircumcised men (8 percent) but only 2 of the circumcised men (1 percent) acquired HIV, even though both groups reported similar frequencies of unprotected sex and sex with prostitutes. The uncircumcised men were about twice as likely to develop genital ulcers but had no more gonorrhea, syphilis, or herpes infections than the circumcised men did, the scientists report in the March 27 Lancet.

Earlier research indicated that HIV could enter a man's body via the soft foreskin. In 2002, Robert C. Bailey of the University of Illinois at Chicago and his colleagues found that foreskin samples from uncircumcised, healthy men harbor less of the protective protein called keratin than other types of skin do.

Moreover, the foreskin has high concentrations of CD4 T and Langerhans' cells, the immune cells typically targeted by HIV, Bailey reported. The concentrations were even greater than those in tissue from women's cervices, which are highly susceptible to HIV infection. When exposed to the virus in a lab dish, the foreskin cells took up six to nine times as much HIV as cervical cells did, Bailey says.

"The hypothesis is that the foreskin contains a lot of cells ... that are magnets for HIV," says Bollinger.

The scientific community remains divided on medical and ethical grounds over the issue of circumcision. However, the case for circumcision as a means to avert HIV transmission appears to be gaining strength, Bailey says.

A 1999 study of 746 Kenyan truck drivers found that uncircumcised men were four times as likely to acquire HIV as circumcised men were, even though the groups reported similar frequencies of unprotected sex and sex with prostitutes. In 2000, a study of healthy Ugandan men in stable relationships with HIV-positive women found that 40 of 137 uncircumcised men acquired HIV from their partners over a 30-month span, whereas none of 50 circumcised men did. Few men in either group used condoms.

Moreover, African countries where the vast majority of men are circumcised--such as Nigeria and Gabon--have HIV-infection rates of less than 5 percent among men. In contrast, Zimbabwe and Botswana, with low circumcision rates, have male HIV-infection rates of 25 percent or higher.

Three rigorous studies currently under way in Africa may further clarify how circumcision affects HIV risk, says Bailey.

Meanwhile, Bollinger emphasizes that any defense afforded by circumcision is incomplete and that men should use condoms for sex outside a monogamous relationship.