Findings From South Africa May Offer Powerful Way To Cut HIV Transmission

By MARK SCHOOFS, SARAH LUECK and MICHAEL M. PHILLIPS Staff Reporters of THE WALL STREET JOURNAL July 5, 2005; Page A1

In a potentially major breakthrough in the campaign against AIDS, French and South African researchers have apparently found that male circumcision reduces by about 70% the risk that men will contract HIV through intercourse with infected women.

Other than abstinence and safer sex, almost nothing has been proved to reduce the sexual spread of HIV, the virus that causes AIDS. World-wide, the major route of HIV transmission for many years has been heterosexual sex.

Vaccine developers have said they would consider an AIDS vaccine with just 30% efficacy useful. But so far, no effective vaccine against the disease has been developed, leaving AIDS workers desperate for another tool to help them stem the tide of new infections, estimated at almost five million last year.

The circumcision findings were so dramatic that the data and safety monitoring board overseeing the research halted the study in February, about nine months before it would have been completed, on the grounds that it would be immoral to proceed without offering the uncircumcised control group the opportunity to undergo the procedure. While men were directly protected from infection by circumcision, women could benefit indirectly because circumcision would reduce the chances their partners would be HIV-positive.

Researchers in the field have been aware of the study's basic findings, but they haven't been published, so most experts haven't evaluated them. The British medical journal the Lancet decided against publishing the study, but for reasons unrelated to the data and scientific content, according to people familiar with the matter. Lancet officials, following standard policy at the journal, refused to comment on why the study was turned down.

The fact that an independent board ordered the study halted is considered a strong sign that the science is sound. Bertran Auvert, the French researcher who headed the trial, declined to discuss the findings but is expected to present them later this month at an International AIDS Society conference in Brazil.

Still, the fact that the research hasn't yet been published makes experts in the field wary about commenting. "Confirm, confirm, confirm," said Seth Berkley, a veteran HIV researcher and president of the International AIDS Vaccine Initiative. But if the study holds up, said Dr. Berkley, who wasn't involved with the research, it would be "quite important" because circumcision would be "an intervention that works over a person's lifetime and could reduce HIV in a community setting."

Assuming circumcision is as effective as the new study shows, it would still require careful implementation. In particular, health experts are concerned that men understand that circumcision can't fully protect them and that they maintain other preventive measures, such as safer sex.

"These preliminary results are quite interesting and we look forward to examining the data more closely, to looking at the technical aspects of the study and public-health implications if these results are confirmed by other trials," said Cate Hankins, chief scientific adviser to the United Nations AIDS agency, UNAIDS. More than 30 previous studies have suggested a relationship between circumcision and lower rates of HIV infection. In Kenya, for example, HIV prevalence is much higher among the Luo people, who don't practice circumcision, than among the Kikuyu, who do.

And there are strong biological theories as to why. For example, a type of cell that HIV targets, called the Langerhans cell, lies close to the delicate underside of the foreskin, whereas the head of a circumcised penis tends to develop a thick layer of outer skin that may armor it against HIV. Another theory: Rather than acting against HIV itself, circumcision may help prevent other sexually transmitted diseases that are known to facilitate the acquisition of HIV.

Despite these theories, no study until now has been able to prove that circumcision reduces the chances of contracting HIV. Longtime advocates of the benefits of circumcision note that performing such a study has always faced resistance because of the sensitive cultural issues involved as well as the challenge of persuading a significant number of men to undergo the procedure. The new research was designed to test the hypothesis by the most rigorous possible method: a randomized, controlled clinical trial.

It was conducted with more than 3,000 HIV-negative men ages 18 to 24 in a South African township called Orange Farm. Half of the men were randomly assigned to be circumcised and the other half to remain uncircumcised as controls. The study, headed by Dr. Auvert, a researcher at the French National Institute of Health and Medical Research and at the University of Versailles Saint-Quentin, originally planned to follow the men for 21 months. But after all the men had been followed for a year -- and about half of them for the full 21 months -- the data showed the circumcised group fared far better. For every 10 uncircumcised men in the study who contracted HIV, only about three circumcised men did so, according to two people familiar with the research and a draft of the study reviewed by The Wall Street Journal.

Stopping trials is common when an intervention is clearly shown to be effective. Indeed, the result of the South African trial is likely to spark discussion of whether to halt or modify two other major studies of circumcision and HIV under way in Kenya and Uganda, funded by the National Institutes of Health.

Ronald Gray, lead researcher on the Uganda trial, said, "It would be extremely unwise" to stop the Kenya and Uganda trials at this stage because "medicine has been burned in the past when policy is based on a single trial."

It isn't clear how the new study, if confirmed, would influence U.S. policy. Circumcision wouldn't affect IV drug users who get infected by sharing syringes, a group that accounts for a large proportion of American HIV cases. Also, the South Africa study didn't evaluate whether circumcision would offer any protection to gay men, who make up another large proportion of American cases. Any direct benefit to gay men would almost certainly be restricted to the insertive partner in anal intercourse, not the receptive partner.

In countries where male circumcision is uncommon and heterosexual HIV rates are high or rising rapidly, the procedure could be a powerful way of reducing the spread of the disease, the new study shows. Even so, researchers warn of potential pitfalls in trying to put the findings into practice. First, circumcision doesn't make a person immune to infection. Indeed, if men abandon safer sex practices because they think the surgery completely protects them, then HIV transmission could rise.

"It will not take very much of an increase in risk behavior to overcome the benefit from circumcision," said Carolyn Williams, an American researcher involved in the Kenya circumcision study. AIDS experts insist that circumcision will have to be accompanied by intensive counseling.

Secondly, AIDS researchers worry that circumcisions performed in unsanitary conditions could lead to dangerous complications.

And while many Africans come from cultures that practice circumcision, many others don't. Would large numbers of men in noncircumcising cultures consent to go under the knife simply to reduce their risk of acquiring HIV?

"It's a surgical procedure on an organ that, you know, conjures up a lot of feelings in people," said Robert Bailey, the principal investigator in the Kenya study. "It's not just a shot in the arm."