Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial

Background: Observational studies have reported an association between male circumcision and reduced risk of HIV infection in female partners. We assessed whether circumcision in HIV-infected men would reduce transmission of the virus to female sexual partners. Methods: 922 uncircumcised, HIV-infected, asymptomatic men aged 15-49 years with CD4-cell counts 350 cells per μL or more were enrolled in this unblinded, randomised controlled trial in Rakai District, Uganda. Men were randomly assigned by computer-generated randomisation sequence to receive immediate circumcision (intervention; n=474) or circumcision delayed for 24 months (control; n=448). HIV-uninfected female partners of the randomised men were concurrently enrolled (intervention, n=93; control, n=70) and followed up at 6, 12, and 24 months, to assess HIV acquisition by male treatment assignment (primary outcome). A modified intention-to-treat (ITT) analysis, which included all concurrently enrolled couples in which the female partner had at least one follow-up visit over 24 months, assessed female HIV acquisition by use of survival analysis and Cox proportional hazards modelling. This trial is registered with ClinicalTrials.gov, number NCT00124878. Findings: The trial was stopped early because of futility. 92 couples in the intervention group and 67 couples in the control group were included in the modified ITT analysis. 17 (18%) women in the intervention group and eight (12%) women in the control group acquired HIV during follow-up (p=0·36). Cumulative probabilities of female HIV infection at 24 months were 21·7% (95% CI 12·7-33·4) in the intervention group and 13·4% (6·7-25·8) in the control group (adjusted hazard ratio 1·49, 95% CI 0·62-3·57; p=0·368). Interpretation: Circumcision of HIV-infected men did not reduce HIV transmission to female partners over 24 months; longer-term effects could not be assessed. Condom use after male circumcision is essential for HIV prevention. Funding: Bill & Melinda Gates Foundation with additional laboratory and training support from the National Institutes of Health and the Fogarty International Center. © 2009 Elsevier Ltd. All rights reserved.