Three randomized trials, including one which is the basis for this proposal, and numerous observational studies demonstrate that male circumcision reduces male HIV acquisition. We conducted an NIH-funded trial of male circumcision for HIV prevention in rural Rakai, Uganda. 5000 HIV-negative male VCT acceptors aged 15-49 were randomized to either immediate circumcision (intervention) or delayed circumcision (controls). The trial was stopped by the DSMB on Dec 12, 2006, when an interim analysis demonstrated reduced HIV acquisition (IRR= 0.52, Cl 0.31-0.86, p = 0.012) and reduced GUD (RR=0.44, Cl 0.33-0.58, p<0.001) in circumcised men. Since GUD is a risk factor for HIV, it is possible that a reduction in STIs which cause GUD contributes to the HIV protective effect of circumcision. Serum and penile swabs were collected at baseline and at 6, 12 and 24 months of follow up, but trial funding did not cover STI assays. The specific aims of this proposal are: 1) To conduct STI assays on stored samples from the trial to determine the efficacy of circumcision in preventing selected STIs. We hypothesize that reduced risks of syphilis and HSV-2 will account for the protection against GUD, and this will contribute to HIV protection. Also circumcision will reduce penile HPV carriage; 2) To assess the long-term effectiveness of circumcision for HIV/STI prevention, and effects on sexual risk behaviors, by conducting an additional 5 years of annual follow up among men who had enrolled in the NIH trial. We hypothesize that circumcised men will have sustained reductions in HIV/STI incidence, and no increase in sexual risk behaviors, both over time and compared to uncircumcised men. Uncircumcised men in the post-trial follow up will include intervention arm crossovers and control arm participants who decline circumcision at the end of the trial (N~380) and, with separate funding, ~1,600 uncircumcised men from the Rakai Community Cohort Study (RCCS), an ongoing HIV/STI surveillance study conducted in villages from which circumcision trial participants were recruited. Because our NIH-funded trial and the proposed post-trial follow up are conducted in parallel to the RCCS, the Rakai setting provides unique opportunities- not available in the other two circumcision trials - to compare risk behaviors in circumcised trial participants with that of uncircumcised men. Assess circumcision acceptability and its effects on HIV incidence in the general population, and to estimate the number of circumcisions and the cost per HIV infection averted. Detailed epidemiological/ behavioral data available on NIH-trial and RCCS participants facilitate adjustment for possible selection bias. Qualitative research will also be conducted to enhance interpretation of findings. We thus propose to assess the long term individual and community effects of circumcision. In this proposal, we request funds for follow-up of NIH trial participants. RCCS participants will be supported by other funding. [unreadable] [unreadable] [unreadable] [unreadable]