Daily Acyclovir to Decrease Herpes Simplex Virus Type 2 (HSV-2) Transmission from HSV-2/HIV-1 Coinfected Persons: A Randomized Controlled Trial

Herpes simplex virus type 2 (HSV-2) is highly prevalent among human immunodeficiency virus type 1 (HIV-1)–infected persons in sub-Saharan Africa [1–4]. Epidemiologic studies suggest synergy between HSV-2 and HIV-1 facilitates the spread of both viruses; HSV-2 reactivation increases HIV-1 concentrations in plasma and genital secretions, increasing the risk of HIV-1 transmission and disease progression, while HIV-1 infection increases HSV-2 shedding and reactivation frequency [5–8]. Thus, coinfection with HIV-1 likely increases the risk of HSV-2 transmission. Daily therapy with valacyclovir reduces HSV-2 transmission in HSV-2–serodiscordant, HIV-1–seronegative-concordant healthy, immunocompetent, heterosexual couples by 48%, likely by decreasing the frequency and amount of HSV-2 shed in the genital tract by the HSV-2–infected partner [9, 10]. HIV-1–infected persons tend to reactivate HSV-2 both more frequently and at higher copy number than their immunocompetent counterparts [7, 8]. It is unknown whether treatment of HSV-2/HIV-1–infected persons with acyclovir reduces transmission of HSV-2 to their HSV-2/HIV-1–susceptible partner. The Partners in Prevention Trial was a double-blind, randomized, controlled trial among HIV-1–serodiscordant couples to determine whether treatment of HSV-2 infection would reduce the transmission of HIV-1. As previously reported, HSV-2 suppression provided to the HIV-1–infected partners did not reduce the risk of HIV-1 transmission to their initially HIV-1–uninfected partners despite a sustained 0.25 log10 copies/mL reduction in the plasma HIV-1 RNA load, a 73% reduction in genital ulcer disease (GUD) incidence, and a 16%–19% decrease in HIV-1 disease progression [3]. We conducted an analysis of the effect of daily acyclovir on the risk of HSV-2 transmission in the subset of participants randomly assigned to receive acyclovir or placebo whose partners who were susceptible to HSV-2 and HIV-1.