Clinical and virologic efficacy of herpes simplex virus type 2 suppression by acyclovir in a multicontinent clinical trial

Abstract

Acyclovir suppressive therapy (400 mg twice daily) reduces herpes simplex virus (HSV) type 2-associated genital ulcer disease and lesional HSV shedding. In an international trial of acyclovir for suppression of HSV type 2 to prevent human immunodeficiency virus (HIV) acquisition (HIV Prevention Trials Network 039), acyclovir had a smaller effect on the frequency of genital ulcer disease as well as a smaller effect on the frequency and quantity of lesional HSV DNA in African women and Peruvian men, compared with its effects in men in the United States. The observed regional variation in the clinical and virologic efficacy of acyclovir for HSV suppression warrants further evaluation of determinants of responses to acyclovir. (ClinicalTrials.gov identifier: NCT00076232.).

Conflict of interest statement

Potential conflicts of interest

CC has received research grant support from GlaxoSmithKline and has served on an advisory board to GlaxoSmithKline. JS has received grant support from GlaxoSmithKline. FC has received research grant support from GlaxoSmithKline. The University of Washington Virology Division has received grant funding from GlaxoSmithKline and Novartis to undertake HSV serological assays and PCR assays for studies funded by these companies. LC directs these laboratories; he receives no salary support from these grants. AW has received grant support from GlaxoSmithKline, Antigenics, and Astellas. All other authors declare no conflict of interest

Financial support: National Institute of Allergy and Infectious Diseases, National Institutes of Health (grants U01 AI052054 and AI30731) and by the HIV Prevention Trials Network (HPTN) under Cooperative Agreement U01 AI46749 sponsored by the National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, National Institute of Drug Abuse, National Institute of Mental Health, and Office of AIDS Research. Dr. Wald is also supported by K24 AI07113. Study drug was purchased with a grant provided by GlaxoSmithKline.

Preliminary data presented at the 15th Conference of Retroviruses and Opportunistic Infections, Boston, MA, 03–06 February 2008 (abstract 32).

The study is registered with Clinicaltrials.gov, number NCT00076232

Figures

Figure 1. Distribution of log 10 HSV PCR copy number isolated from GUD, by Arm and Group

Comparison of HSV DNA copy number from genital ulcers by study arm and region from 861 swabs with detectable HSV. Number of swabs (N), mean, median and standard deviation of the HSV DNA log10 copy number is provided for participants randomized to placebo (left column) and acyclovir (right column).