HIV this week

Observational studies have reported an association between male circumcision and reduced risk of HIV infection in female partners. Wawer and colleagues set out to assess whether circumcision in HIV-infected men would reduce transmission of the virus to female sexual partners. 922 uncircumcised, HIV-infected, asymptomatic men aged 15-49 years with CD4- cell counts 350 cells per microL 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. 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). 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.

HIV this week Editors’ note:

When this trial was stopped for futility because it lacked the power to answer the question of whether or not HIV-positive men who get circumcised are less likely to transmit HIV, it became clear that we would likely never know the definitive answer to this question. However, a key insight gained from the trial is the importance of sexual abstinence until complete wound healing. Premature resumption of sex may delay wound healing, increase the risk that a man may acquire a new HIV infection, and increase the risk of HIV transmission to sexual partners.

These researchers previously found that 93% of HIV-positive men circumcised at CD4 › 350 cells were healed by 6 weeks postcircumcision. However, in this trial, 22% of couples resumed sex early and 25% of the men had not disclosed their HIV status, underscoring the importance of joint couple counselling and testing to learn serostatus and plan abstinence strategies for the healing period.