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

Abstract

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.