Medical Male Circumcision and Herpes Simplex Virus 2 Acquisition: Posttrial Surveillance in Kisumu, Kenya

Three randomized controlled trials have shown that medical male circumcision (MMC) reduces the risk of human immunodeficiency virus (HIV) acquisition in heterosexual men by approximately 60% [1–3], and this protective effect is maintained several years after circumcision [4, 5]. The World Health Organization recommends MMC as an important element of HIV prevention programs [6]. One of the mechanisms by which MMC reduces risk of HIV seroconversion is through reduction of cofactors, such as herpes simplex virus 2 (HSV-2). In the MMC trial in Rakai, Uganda, circumcision resulted in a 28% (95% confidence interval [CI], 8%–44%) reduction in HSV-2 acquisition [7], similar to the 30% (95% CI, 1%–51%) reduction in HSV-2 incidence observed among Orange Farm, South Africa, MMC trial participants [8]. The extent to which MMC protects against HIV through reduction of HSV-2 is important for understanding how to maximize HIV prevention among men seeking circumcision and those choosing to remain uncircumcised. Among Orange Farm trial participants, authors estimated that 28% (95% CI, 18%–37%) of HIV infections may have been due to HSV-2 infection [8], and 11% (95% CI, 5%–38%) in the Rakai trial [9]. In contrast, in our trial in Kisumu, Kenya, at 24 months of follow-up, MMC was not protective against HSV-2, with an adjusted hazard ratio (HR) of 0.94 (95% CI, .70–1.25) [10]. To further understand the discrepancy in findings from our trial and the Ugandan and South African MMC trials, we assessed the efficacy of MMC against HSV-2 incidence under posttrial surveillance conditions, and examined independent risks for HSV-2 acquisition.