Daily acyclovir to decrease herpes simplex virus type 2 (HSV-2) transmission from HSV-2/HIV-1 coinfected persons: a randomized controlled trial

J Infect Dis. 2013 Nov 1;208(9):1366-74. doi: 10.1093/infdis/jit333. Epub 2013 Jul 30.

Abstract

Background: Daily suppressive therapy with valacyclovir reduces risk of sexual transmission of herpes simplex virus type 2 (HSV-2) in HSV-2-serodiscordant heterosexual couples by 48%. Whether suppressive therapy reduces HSV-2 transmission from persons coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) is unknown.

Methods: Within a randomized trial of daily acyclovir 400 mg twice daily in African HIV-1 serodiscordant couples, in which the HIV-1-infected partner was HSV-2 seropositive, we identified partnerships in which HIV-1-susceptible partners were HSV-2 seronegative to estimate the effect of acyclovir on risk of HSV-2 transmission.

Results: We randomly assigned 911 HSV-2/HIV-1-serodiscordant couples to daily receipt of acyclovir or placebo. We observed 68 HSV-2 seroconversions, 40 and 28 in acyclovir and placebo groups, respectively (HSV-2 incidence, 5.1 cases per 100 person-years; hazard ratio [HR], 1.35 [95% confidence interval, .83-2.20]; P = .22). Among HSV-2-susceptible women, vaginal drying practices (adjusted HR, 44.35; P = .004) and unprotected sex (adjusted HR, 9.91; P = .002) were significant risk factors for HSV-2 acquisition; having more children was protective (adjusted HR, 0.47 per additional child; P = .012). Among HSV-2-susceptible men, only age ≤30 years was associated with increased risk of HSV-2 acquisition (P = .016).

Conclusions: Treatment of African HSV-2/HIV-1-infected persons with daily suppressive acyclovir did not decrease risk of HSV-2 transmission to susceptible partners. More-effective prevention strategies to reduce HSV-2 transmission from HIV-1-infected persons are needed.

Keywords: Africa; HIV-1; HSV-2; acyclovir; serodiscordant couples; transmission.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyclovir / administration & dosage*
  • Adult
  • Antiviral Agents / administration & dosage*
  • Coinfection / drug therapy*
  • Coinfection / epidemiology
  • Coinfection / virology
  • Drug Administration Schedule
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • HIV Infections / virology
  • HIV-1*
  • Herpes Genitalis / epidemiology
  • Herpes Genitalis / prevention & control*
  • Herpes Genitalis / transmission
  • Herpesvirus 2, Human / drug effects*
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Male
  • Multivariate Analysis
  • Proportional Hazards Models
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Acyclovir