Circumcision status and incident herpes simplex virus type 2 infection, genital ulcer disease, and HIV infection

Objective: We assessed the protective effect of medical male circumcision (MMC) against HIV, herpes simplex virus type 2 (HSV-2), and genital ulcer disease (GUD) incidence. Design: Two thousand, seven hundred and eighty-seven men aged 18-24 years living in Kisumu, Kenya were randomly assigned to circumcision (n = 1391) or delayed circumcision (n = 1393) and assessed by HIV and HSV-2 testing and medical examinations during follow-ups at 1, 3, 6, 12, 18, and 24 months. Methods: Cox regression estimated the risk ratio of each outcome (incident HIV, GUD, HSV-2) for circumcision status and multivariable models estimated HIV risk associated with HSV-2, GUD, and circumcision status as time-varying covariates. Results: HIV incidence was 1.42 per 100 person-years. Circumcision was 62% protective against HIV [risk ratio = 0.38; 95% confidence interval (CI) 0.22-0.67] and did not change when controlling for HSV-2 and GUD (risk ratio = 0.39; 95% CI 0.23-0.69). GUD incidence was halved among circumcised men (risk ratio = 0.52; 95% CI 0.37-0.73). HSV-2 incidence did not differ by circumcision status (risk ratio = 0.94; 95% CI 0.70-1.25). In the multivariable model, HIV seroconversions were tripled (risk ratio = 3.44; 95% CI 1.52-7.80) among men with incident HSV-2 and seven times greater (risk ratio = 6.98; 95% CI 3.50-13.9) for men with GUD. Conclusion: Contrary to findings from the South African and Ugandan trials, the protective effect of MMC against HIV was independent of GUD and HSV-2, and MMC had no effect on HSV-2 incidence. Determining the causes of GUD is necessary to reduce associated HIV risk and to understand how circumcision confers protection against GUD and HIV. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins