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The Kindest Cut

By Brian W. Simpson

Among the pantheon of HIV prevention strategies, there's always room for another inexpensive and effective solution. Researchers at the Rakai Health Sciences Program in Uganda are conducting a trial to determine whether male circumcision can help stem the AIDS epidemic. It has long been noted that the HIV rates are highest in parts of eastern and southern Africa where male circumcision (surgical removal of the penis's foreskin) is seldom practiced. The inner layer of foreskin, called mucosa, is rich in HIV target cells. (The penis's outer layer is like normal skin and is more impervious to HIV.)

In the late 1990s, the Rakai program confirmed that circumcised men were less likely to acquire HIV. However, that finding from observational studies could have been due to cultural reasons—most circumcised men in Rakai are Muslims who abstain from alcohol and regularly clean themselves after intercourse. Thus, only formal trials could answer the question. A recent South African trial reported that circumcision could reduce a man's chances of becoming HIV infected by about 60 percent. (WHO and NIH recommended the Rakai trial continue.)

The NIH-funded Rakai trial enrolled 5,000 HIV-negative men and randomly assigned them to be circumcised immediately or in two years. In a complementary trial funded by the Bill & Melinda Gates Foundation, HIV-positive men are randomly selected for immediate or delayed circumcision, and their wives are followed to assess whether male circumcision reduces HIV transmission to women. (All participants are given condoms and intensive HIV prevention education.)

If the Rakai trial and separate Kenyan research have positive results, global health officials may add another "C" to HIV prevention's ABC mantra of Abstinence, Being faithful and Condoms.

Once word spread that Rakai was testing circumcision as a potential protection against AIDS, recruiting participants was easy. "We were surprised. It was harder to tell them to wait than to convince them to come for the procedure," says Godfrey Kigozi, MBChB, MPH '00, a Rakai co-principal investigator. The first-rate operating theater also impressed participants, says Valerian Kiggundu, who has performed more than 600 circumcisions for the study. One patient told a friend, "You feel like you're in America when you get in that room."

The researchers are anxiously awaiting the study's outcome. David Serwadda, a Rakai program founder, expects that interim analyses will be reviewed this summer and the trial completed in 2007. "We hope this may be another monumental intervention, but it may not be," Serwadda says. "People keep asking us, 'Suppose [circumcision] is not effective—wouldn't that be devastating?' I say, we don't know for sure. That's why we do these trials."