title: Daily acyclovir to decrease herpes simplex virus type 2 (HSV-2) transmission from HSV-2/HIV-1 coinfected persons: a randomized controlled trial.
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.
authors.affiliation: Department of Global Health.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mujugira
authors.forename: Amalia S
authors.initials: AS
authors.lastname: Magaret
authors.forename: Connie
authors.initials: C
authors.lastname: Celum
authors.forename: Jared M
authors.initials: JM
authors.lastname: Baeten
authors.forename: Jairam R
authors.initials: JR
authors.lastname: Lingappa
authors.forename: Rhoda Ashley
authors.initials: RA
authors.lastname: Morrow
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Fife
authors.forename: Sinead
authors.initials: S
authors.lastname: Delany-Moretlwe
authors.forename: Guy
authors.initials: G
authors.lastname: de Bruyn
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Bukusi
authors.forename: Etienne
authors.initials: E
authors.lastname: Karita
authors.forename: Saidi
authors.initials: S
authors.lastname: Kapiga
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage*; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D060085:Coinfection / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D015497:HIV-1; D006558:Herpes Genitalis / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000212:Acyclovir
keywords: Africa; HIV-1; HSV-2; acyclovir; serodiscordant couples; transmission
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