Oral and Vaginal Tenofovir for Genital Herpes Simplex Virus Type 2 Shedding in Immunocompetent Women: A Double-Blind, Randomized, Cross-over Trial

J Infect Dis. 2015 Dec 15;212(12):1949-56. doi: 10.1093/infdis/jiv317. Epub 2015 Jun 4.


Background: Tenofovir is a potent anti-human immunodeficiency virus (HIV) agent that decreased risk of herpes simplex virus type 2 (HSV-2) acquisition in HIV pre-exposure prophylaxis trials. Whether tenofovir has utility in established HSV-2 disease is unclear.

Methods: We randomized immunocompetent women with symptomatic HSV-2 infection to oral tenofovir disoproxil fumarate (TDF)/placebo vaginal gel, oral placebo/tenofovir (TFV) vaginal gel, or double placebo (ratio 2:2:1) in a one-way cross-over trial. Women collected genital swabs twice daily for HSV PCR during 4-week lead-in and 5-week treatment phases. The primary intent-to-treat end point was within-person comparison of genital HSV shedding and lesion rates.

Results: 64 women completed the lead-in phase and were randomized. Neither TDF nor TFV gel decreased overall shedding or lesion rate in the primary analysis; TFV gel decreased quantity of HSV DNA by -0.50 (-0.86-0.13) log10 copies/mL. In the per-protocol analysis, TDF reduced shedding (relative risk [RR] = 0.74, P = .006) and lesion rates (RR = 0.75, P = .032); quantity of virus shed decreased by 0.41 log10 copies/mL.

Conclusions: Oral TDF modestly decreased HSV shedding and lesion rate, and quantity of virus shed when used consistently. Vaginal TFV gel decreased quantity of virus shed by 60%. In contrast to effects on HSV-2 acquisition, tenofovir is unlikely to provide clinically meaningful reductions in the frequency of HSV shedding or genital lesions.

Clinical trials registration: NCT01448616.

Keywords: HIV acquisition; HSV-2 transmission; genital herpes; herpes simplex virus-2 (HSV-2); tenofovir; vaginal microbicide.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravaginal
  • Administration, Oral
  • Adult
  • Antiviral Agents / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Herpes Genitalis / drug therapy*
  • Herpes Genitalis / pathology
  • Herpesvirus 2, Human / isolation & purification*
  • Humans
  • Middle Aged
  • Placebos / administration & dosage
  • Tenofovir / therapeutic use*
  • Treatment Outcome
  • Virus Shedding*


  • Antiviral Agents
  • Placebos
  • Tenofovir

Associated data

  • ClinicalTrials.gov/NCT01448616