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Circumcision to Prevent HIV: A Promising Strategy Raises Provocative Questions

Circumcision in high-risk adult males lowers their rate of HIV infection, but will this procedure be culturally acceptable?

As access to antiretroviral therapy for HIV-infected people slowly penetrates the developing world, preventing new HIV infections remains a high priority. Unfortunately, efforts to lower transmission rates through behavior change and use of vaginal microbicides generally have been disappointing, and an HIV vaccine remains only a distant hope.

In December 2006, the NIH announced the early termination of two randomized controlled studies of adult male circumcision in Kenya and Uganda after interim analyses showed that, in each trial, HIV incidence was halved among men who had been circumcised compared with those who had not. In both trials, researchers randomized uncircumcised, HIV-negative men to surgical circumcision either immediately or after a delay of 24 months; all participants were given risk-reduction counseling and condoms. No differences in risk behaviors were observed between groups in either study nor were severe complications of surgery seen (Journal Watch Mar 13 2007).

Based on these studies, an editorialist called male circumcision "the most compelling evidence-based [HIV] prevention strategy to emerge since the results from mother-to-child transmission clinical trials." Epidemiologic modeling suggested that, in southern Africa alone, widespread male circumcision could prevent 2 million new HIV infections and 300,000 deaths in the next decade. The huge potential benefits of this strategy immediately brought forth new questions: What might be the direct and indirect effects on male-to-female transmission? What is the optimal age for circumcision? How can resources be deployed to maximize benefits and minimize risks? Will circumcision be accepted in different cultures? How can circumcision be promoted without undermining education about condom use and campaigns against female genital mutilation?

Finally, what are the implications of these findings for advice on newborn circumcision in developed countries? In a study published in 2006, uncircumcised men in a New Zealand birth cohort were more than three times as likely as circumcised men to have sexually transmitted infections between age 18 and age 25 (Journal Watch Dec 7 2006). Other evidence suggests that circumcision lowers risk for urinary tract infections, genital ulcer disease, penile cancer, and, perhaps, transmission of human papillomavirus. The perceived benefits of newborn circumcision in any setting will depend on the perceived risks for these negative outcomes. The new data on HIV and sexually transmitted diseases could shift the discussion perceptibly toward advocacy for circumcision in the developed world, particularly among groups perceived to be at greatest risk for HIV infection.

Bruce Soloway, MD

Published in Journal Watch General Medicine December 28, 2007

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