BACKGROUND: Male circumcision is associated with reduced HIV acquisition. METHODS: HIV acquisition was determined in a cohort of 5507 HIV-negative Ugandan men, and in 187 HIV-negative men in discordant relationships. Transmission was determined in 223 HIV-positive men with HIV-negative partners. HIV incidence per 100 person years (py) and adjusted rate ratios (RR) and 95% confidence intervals (CI) were estimated by Poisson regression. HIV-1 serum viral load was determined for the seropositive partners in HIV-discordant couples. RESULTS: The prevalence of circumcision was 16.5% for all men; 99.1% in Muslims and 3.7% in non-Muslims. Circumcision was significantly associated with reduced HIV acquisition in the cohort as a whole (RR 0.53, CI 0.33-0.87), but not among non-Muslim men. Prepubertal circumcision significantly reduced HIV acquisition (RR 0.49, CI 0.26-0.82), but postpubertal circumcision did not. In discordant couples with HIV-negative men, no serconversions occurred in 50 circumcised men, whereas HIV acquisition was 16.7 per 100 py in uncircumcised men (P = 0.004). In couples with HIV-positive men, HIV transmission was significantly reduced in circumcised men with HIV viral loads less than 50000 copies/ml (P = 0.02). INTERPRETATION: Prepubertal circumcision may reduce male HIV acquisition in a general population, but the protective effects are confounded by cultural and behavioral factors in Muslims. In discordant couples, circumcision reduces HIV acquisition and transmission. The assessment of circumcision for HIV prevention is complex and requires randomized trials.
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