Medical male circumcision and herpes simplex virus 2 acquisition: posttrial surveillance in Kisumu, Kenya

Abstract

Background: We estimated the 72-month efficacy of medical male circumcision (MMC) against herpes simplex virus 2 (HSV-2) incidence among men in the Kisumu MMC randomized trial.

Methods: From 2002 to 2005, 2784 men aged 18-24 were enrolled and randomized 1:1 to immediate circumcision or control. Cox proportional hazards regression incorporating stabilized inverse probability of treatment and censoring weights generated through marginal structural modeling was used to estimate the efficacy of MMC on HSV-2 risk. Conventional conditional Cox regression identified multivariable risks for HSV-2 seroconversion.

Results: Among 2044 HSV-2 seronegative men at baseline, the cumulative 72-month HSV-2 incidence was 33.5% (32.7% among circumcised men, 34.6% among uncircumcised men). In weight-adjusted Cox regression, the hazard ratio was 0.88 (95% confidence interval, .77-1.10). In multivariable analyses, risks for HSV-2 included human immunodeficiency virus (HIV) infection, genital ulcer disease (GUD), penile epithelial trauma, multiple recent sex partners, and being married /cohabiting.

Conclusions: MMC had no effect on acquisition of HSV-2 during 72 months of follow-up. The temporal sequence and limited correlation between HSV-2, GUD, and penile epithelial trauma suggests that these are distinct phenomena rather than misclassification of HSV-2 symptoms. Determining the etiology of non-sexually transmitted infection GUD and penile epithelial trauma is needed, as both are commonly occurring risks for HSV-2 and HIV acquisition.

Clinical trials registration: NCT0005937.

Trial registration: ClinicalTrials.gov NCT00005937.

Keywords: HIV; HSV-2; Kenya; genital ulcer disease; male circumcision; penile epithelial injury.

Figures

Figure 1.

Cumulative herpes simplex virus 2 (HSV-2) incidence across follow-up visits by circumcision status. Abbreviation: CI, confidence interval.

Figure 2.

Proportional Venn diagram depicting the relationship between herpes simplex 2 (HSV-2), genital ulcer disease (GUD), and penile epithelial trauma (defined as self-reported scratches, cuts, abrasions, or bleeding of the penile skin occurring during or after sex in the past 6 months). Area-proportional Venn diagram showing the relative frequency and overlap of HSV-2 (n = 404), GUD (n = 156), and penile epithelial trauma (n = 1378). Numbers represent unique subjects: overlap represents events occurring within a single subject observed at the same time (simultaneous) or at different time points. Percentages reflect the proportion of the total number of men (N = 1471) with HSV-2, GUD, or penile epithelial trauma.