title: Impact of suppressive herpes therapy on genital HIV-1 RNA among women taking antiretroviral therapy: a randomized controlled trial.
abstract: OBJECTIVE
  To demonstrate a causal relationship between herpes simplex virus 2 (HSV-2) and increased genital HIV-1-RNA shedding in women on HAART.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled trial of herpes-suppressive therapy (valacyclovir 500 mg twice a day) in HIV-1/HSV-2-infected women taking HAART in Burkina Faso.
  
  
  METHODS
  Participants were followed for a total of 12 biweekly visits before and after randomization. The presence and frequency of genital and plasma HIV-1 RNA, and of genital HSV-2 were assessed using summary measures, adjusting for baseline values. Random effect linear regression models were used to assess the impact of treatment on genital and plasma viral loads among visits with detectable virus.
  
  
  RESULTS
  Sixty women were enrolled into the trial. Their median CD4 lymphocyte count was 228 cells/mul, and 83% had undetectable plasma HIV-1 RNA at baseline. Valacyclovir reduced the proportion of visits with detectable genital HSV-2 DNA [odds ratio (OR) 0.37, 95% confidence interval (CI) 0.13, 1.05], but had no significant impact on the frequency (OR 0.90, 95% CI 0.31, 2.62) or quantity (reduction of 0.33 log copies/ml, 95% CI -0.81, 0.16) of genital HIV-1 RNA. However, according to pre-defined secondary analyses restricted to women who shed HIV-1 at least once in the baseline phase, valacyclovir reduced both the proportion of visits with detectable HIV-1 shedding (OR 0.27, 95% CI 0.07, 0.99) and the quantity of genital HIV-1 RNA during these visits (-0.71 log10 copies/ml, 95% CI -1.27, -0.14).
  
  
  CONCLUSIONS
  HSV-2 facilitates residual genital HIV-1 replication among dually infected women taking HAART despite HIV-1 suppression at the systemic level.
authors.affiliation: Centre Muraz, Bobo-Dioulasso, Burkina Faso.
authors.forename: Abdoulaye
authors.initials: A
authors.lastname: Ouedraogo
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nagot
authors.forename: Laurence
authors.initials: L
authors.lastname: Vergne
authors.forename: Issouf
authors.initials: I
authors.lastname: Konate
authors.forename: Helen A
authors.initials: HA
authors.lastname: Weiss
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Defer
authors.forename: Vincent
authors.initials: V
authors.lastname: Foulongne
authors.forename: Anselme
authors.initials: A
authors.lastname: Sanon
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Andonaba
authors.forename: Michel
authors.initials: M
authors.lastname: Segondy
authors.forename: Philippe
authors.initials: P
authors.lastname: Mayaud
authors.forename: Philippe
authors.initials: P
authors.lastname: Van de Perre
mesh_terms: D000212:Acyclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D005836:Genitalia, Female / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006558:Herpes Genitalis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000276:immunology*; D014456:Ulcer / Q000276:immunology; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir