Circumcision Status and Incident HSV-2 Infection, Genital Ulcer Disease, and HIV Infection

Objective: We assessed the protective effect of medical male circumcision (MMC) against HIV, HSV-2, and GUD incidence. Design: 2784 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 (RR) 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 [RR=0.38; 95% CI: 0.22 - 0.67], and did not change when controlling for HSV-2 and GUD [RR=0.39; 95% CI: 0.23 - 0.69]. GUD incidence was halved among circumcised men [RR=0.52, 95% CI: 0.37 - 0.73]. HSV-2 incidence did not differ by circumcision status [RR=0.94; 95% CI: 0.70 - 1.25]. In the multivariable model, HIV seroconversions were tripled [RR=3.44; 95% CI: 1.52 - 7.80] among men with incident HSV-2 and 7 times greater [RR=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.