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 in which HIV acquisition was reduced by 60% after 24 months. METHODS: From 2002 to 2005 2784 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 to 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% confidence interval (CI): 5.98-8.68%]: 4.81% among circumcised men 11.0% among uncircumcised men. The crude hazard ratio of HIV seroconversion for circumcised vs. uncircumcised men was 0.38 [95% CI: 0.26-0.55]. In weight-adjusted Cox regression the hazard ratio was 0.42 [95% CI: 0.26-0.66]. CONCLUSION: 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.