title: Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus.
abstract: BACKGROUND
  Epidemiologic data suggest that infection with herpes simplex virus type 2 (HSV-2) is associated with increased genital shedding of human immunodeficiency virus type 1 (HIV-1) RNA and HIV-1 transmissibility.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled trial of HSV suppressive therapy with valacyclovir (at a dose of 500 mg twice daily) in Burkina Faso among women who were seropositive for HIV-1 and HSV-2; all were ineligible for highly active antiretroviral therapy. The patients were followed for 24 weeks (12 weeks before and 12 weeks after randomization). Regression models were used to assess the effect of valacyclovir on the presence and quantity of genital and plasma HIV-1 RNA and genital HSV-2 DNA during treatment, adjusting for baseline values, and to evaluate the effect over time.
  
  
  RESULTS
  A total of 140 women were randomly assigned to treatment groups; 136 were included in the analyses. At enrollment, the median CD4 cell count was 446 cells per cubic millimeter, and the mean plasma viral load was 4.44 log10 copies per milliliter. With the use of summary-measures analysis, valacyclovir therapy was found to be associated with a significant decrease in the frequency of genital HIV-1 RNA (odds ratio, 0.41; 95% confidence interval [CI], 0.21 to 0.80) and in the mean quantity of the virus (log(10) copies per milliliter, -0.29; 95% CI, -0.44 to -0.15). However, there was no significant decrease in detection of HIV (risk ratio, 0.93; 95% CI, 0.81 to 1.07). HSV suppressive therapy also reduced the mean plasma HIV-1 RNA level by 0.53 log(10) copy per milliliter (95% CI, -0.72 to -0.35). Repeated-measures analysis showed that these effects became significantly stronger during the 3 months of follow-up.
  
  
  CONCLUSIONS
  HSV suppressive therapy significantly reduces genital and plasma HIV-1 RNA levels in dually infected women. This finding may have important implications for HIV control. (ClinicalTrials.gov number, NCT00158509 [ClinicalTrials.gov].).
authors.affiliation: Centre Muraz, Bobo-Dioulasso, Burkina Faso. n_nagot@hotmail.com
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nagot
authors.forename: Abdoulaye
authors.initials: A
authors.lastname: Ouédraogo
authors.forename: Vincent
authors.initials: V
authors.lastname: Foulongne
authors.forename: Issouf
authors.initials: I
authors.lastname: Konaté
authors.forename: Helen A
authors.initials: HA
authors.lastname: Weiss
authors.forename: Laurence
authors.initials: L
authors.lastname: Vergne
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Defer
authors.forename: Didier
authors.initials: D
authors.lastname: Djagbaré
authors.forename: Anselme
authors.initials: A
authors.lastname: Sanon
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Andonaba
authors.forename: Pierre
authors.initials: P
authors.lastname: Becquart
authors.forename: Michel
authors.initials: M
authors.lastname: Segondy
authors.forename: Roselyne
authors.initials: R
authors.lastname: Vallo
authors.forename: Adrien
authors.initials: A
authors.lastname: Sawadogo
authors.forename: Philippe
authors.initials: P
authors.lastname: Van de Perre
authors.forename: Philippe
authors.initials: P
authors.lastname: Mayaud
mesh_terms: D000212:Acyclovir / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002584:Cervix Uteri / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D006558:Herpes Genitalis / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D012367:RNA, Viral / Q000032:analysis* / Q000097:blood; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects; D017201:Virus Shedding / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir