At the very least, Vermund notes, the foreskin increases contact time with the virus following unprotected sexual intercourse when infectious fluid becomes trapped.
Although the benefits and efficacy of circumcision are now well documented for heterosexual men, the role of foreskin removal in homosexual men remains an open question. To date, no clinical trial has been conducted to assess if circumcision may be protective for this population. But researchers recently combined the results of 15 observational studies in a meta-analysis conducted in the U.S., Europe and several developing nations involving over 53,000 homosexual men to determine if any evidence for protection exists.
Mathematical analyses indicated that HIV risk was reduced by 14 percent in circumcised homosexual men across the studies, but "the results were not statistically significant, pointing to the possibility that circumcision may not have a substantial effect on HIV infection in men who have sex with men," says Gregorio Millett, study author and a behavioral scientist at the U.S. Centers for Disease Control and Prevention in Atlanta.
The difficulty in evaluating circumcision for homosexual populations, notes Gray, is that most studies do not carefully evaluate sexual practices. Although foreskin removal protects men engaged in anal intercourse (in the same manner as it benefits heterosexual men), "nothing about circumcision protects receptive men as the rectal area is exposed to HIV," Vermund says. The issue will likely remain unresolved until more data can be gathered from studies specifically designed to address the effects of circumcision on the various subgroups of homosexual men.
Current recommendations from the World Health Organization (WHO) in Geneva, Switzerland, call for large-scale circumcision campaigns in countries with high infection rates. For sub-Saharan Africa (where heterosexual sex is primarily responsible for the HIV epidemic), circumcision has the potential to dramatically reduce the toll of the virus, which WHO estimates of up to 5.7 million new infections and three million deaths averted over the next 20 years.
Fauci does not foresee a broad mandate for circumcising infants in the U.S., however, where the practice is already common. "Although circumcision could be beneficial," he says, "HIV is not a disease of the general population here."
Despite the protective effect of circumcision, condoms remain a key component of HIV prevention, because there is "no surgical way to remove all of the inner foreskin," cautions Roger Short, a reproductive biologist at the University of Melbourne in Australia.
In the future, alternatives to circumcision may become available for those men with social or religious objections to the practice. Estrogen creams have recently been proposed as their application sparks a rapid deposition of keratin in the foreskin. If the foreskin can be sufficiently reinforced with keratin to provide a barrier for the Langerhans cells, Short says, a weekly topical application of estrogen could augment or even replace circumcision. For now, however, researchers remain skeptical, as estrogen may also increase the number of HIV receptors on the surface of target cells.
The bottom line: circumcision protects heterosexual men from HIV acquisition via sexual intercourse with the greatest benefits accruing in developing nations that are hardest hit by the epidemic.