Tenofovir Gel for Prevention of Herpes Simplex Virus Type 2 Acquisition: Findings From the VOICE Trial

J Infect Dis. 2019 May 24;219(12):1940-1947. doi: 10.1093/infdis/jiz045.


Background: Genital infection with herpes simplex virus type 2 (HSV-2) is common and increases risk of human immunodeficiency virus (HIV) transmission and acquisition. Pericoital use of tenofovir (TFV) gel provided protection from HSV-2 acquisition in the CAPRISA 004 study.

Methods: We measured estimate of effect of vaginal TFV 1% gel in preventing HSV-2 acquisition among women in VOICE, randomized, double-blinded, placebo-controlled trial assessing daily use of oral and vaginal TFV for HIV-1 preexposure prophylaxis. The TFV level in plasma at the first quarterly visit was used as a measure of gel use.

Results: Of 566 participants at risk for HSV-2 acquisition, 532 (94%) had first-quarter plasma TFV and end-of-study HSV-2 serologic data available. Over a follow-up period of 501 person-years, 92 incident cases of HSV-2 acquisition occurred: 77 were in women with no TFV detected in plasma, and 15 occurred in women with TFV detected in plasma (incidence, 20.6 cases/100 person-years [95% confidence interval [CI], 16.2-25.7] vs 11.9 cases/100 person-years [95% CI, 6.6-19.6], respectively). TFV detection in plasma was associated with a trend toward a reduced risk of HSV-2 seroconversion, with an unadjusted hazard ratio (HR) of 0.59 (95% CI, .34-1.02; P = .060) and a HR adjusted for site, age, having ≥2 male sex partners in the past 3 months, use of hormonal contraception, having anal sex in the past 3 months, and HIV status of 0.60 (95% CI, .33-1.08; P = .086).

Conclusions: Detection of TFV in plasma among TFV gel users was associated with a trend toward a reduced risk of HSV-2 acquisition, after controlling for sexual behavior and HIV-1 acquisition.

Keywords: HIV-1; Herpes simplex virus; genital herpes; preexposure prophylaxis; tenofovir.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Antiviral Agents / therapeutic use*
  • Double-Blind Method
  • Female
  • HIV Infections / complications
  • HIV Infections / virology
  • HIV-1
  • Herpes Genitalis / prevention & control*
  • Herpes Genitalis / virology
  • Herpesvirus 2, Human / drug effects*
  • Humans
  • Incidence
  • Pre-Exposure Prophylaxis / methods
  • Sexual Behavior
  • Tenofovir / therapeutic use*
  • Vaginal Creams, Foams, and Jellies / therapeutic use*
  • Young Adult


  • Antiviral Agents
  • Vaginal Creams, Foams, and Jellies
  • Tenofovir