The Long Term Efficacy of Medical Male Circumcision against HIV Acquisition

BACKGROUND:: In three randomized trials, medical male circumcision (MMC) reduced HIV acquisition in heterosexual men in sub-Saharan Africa by approximately 60%, after 21-24 months of follow-up. We estimated the 72-month efficacy of MMC against HIV among men retained in the Kisumu randomized trial, where HIV acquisition was reduced by 60% after 24 months. METHODS:: From 2002-2005, 2,784 men aged 18-24 were enrolled and randomized 1:1 to immediate circumcision or control. At trial end in December 2006, control men were offered free circumcision. Follow-up continued through September 2010. Cox proportional hazards regression incorporating stabilized inverse probability of treatment and censoring weights generated through marginal structural modeling, was used to account for potential time-varying confounding and censoring to estimate the efficacy of MMC on HIV risk. RESULTS:: The cumulative 72-month HIV incidence was 7.21% [95% CI: 5.98-8.68%]: 4.81% among circumcised men, 11.0% among uncircumcised men. The crude hazard ratio (HR) of HIV seroconversion for circumcised vs. uncircumcised men was 0.38 [95% CI: 0.26-0.55]. In weight-adjusted Cox regression, the HR was 0.42 [95% CI: 0.26-0.66]. CONCLUSIONS:: The efficacy of MMC was sustained at 58% at 72 months, similar to overall findings of the three trials under conditions of randomization. These findings provide an estimate of the long-term efficacy of circumcision against HIV acquisition. Our results support programmatic scale-up recommendations that are based on assumptions of sustained efficacy.