When scientists announced in July that circumcising adult males can drastically cut the rate of HIV infection, international agencies urged caution, saying it would be best to wait for results from further studies. But in South Africa, where HIV prevalence is the highest in the world, some experts say there's little time to waste.

Since 1986, there have been more than 40 observational and biological studies indicating that circumcision can protect men from HIV infection (Lancet 5, 165–172; 2005, AIDS 14, 2361–2370; 2000). But the latest study, led by the Agence Nationale de Recherches sur le SIDA in Paris, is the first randomized control trial.

The researchers followed 3,274 sexually active men between the ages of 18 and 24 in the poor, high-risk community of Orange Farm near Johannesburg. Circumcising the men cut their risk of infection with HIV by about 60%, they found. Two other large randomized trials funded by the US National Institutes of Health are under way in Uganda and Kenya (PLoS Med. 2, e293).

One controlled trial done in a particular context is not sufficiently strong evidence to start implementing wide-scale policy change. Jimmy Volmink, South African Cochrane Centre

In some studies, as many as 70% of participants said they would be willing to be circumcised if it could protect them from HIV infection, notes Bertran Auvert, lead investigator of the French study. The next step, he says, is to implement circumcision along with other interventions such as condoms and STD clinics.

But others are more cautious. “I think if the studies consistently show an effect, then we're looking at a potentially valuable intervention for controlling HIV transmission,” says Jimmy Volmink, director of the South African Medical Research Council's Cochrane Centre. Although the study shows some protection, it's not clear whether that protection will remain effective in the long term, he says. “I feel one controlled trial done in a particular context is not sufficiently strong evidence to start implementing wide-scale policy change.”

Before applying the results, scientists will have to consider cultural issues, Volmink adds. For example, some South African tribes such as the Xhosa and the Pedi follow certain rituals in circumcising young men. In July, local newspapers reported that more than 20 young men had died in South Africa as the result of botched circumcisions. In some cases, practitioners use the same blade to circumcise several boys, potentially increasing the risk of HIV infection. Spreading the message that circumcision prevents HIV infection could increase the number of unskilled—and unsafe—practitioners, he says.

There are biological reasons that might explain how circumcision cuts HIV risk. Langerhans immune cells found under the foreskin are prime targets for HIV. The virus can also survive longer in the moist environment between the glans and foreskin. Because lesions from sexually transmitted diseases that increase the risk of HIV infection often occur under the foreskin, removing it could reduce the risk. Circumcision may also reduce the risk of invasive penile cancer in men and cervical cancer in their female partners.

The ongoing studies are likely to confirm circumcision's protective effect in HIV infection, so policymakers should start planning to implement it now, says Francois Venter, clinical director of South Africa's Reproductive Health Research Unit. “If we had an AIDS vaccine this good, we would roll it out tomorrow,” he says. “There wouldn't be a debate. We would vaccinate the whole country.”