title: A randomised placebo-controlled trial to explore the effect of suppressive therapy with acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 among Zimbabwean sex workers.
abstract: OBJECTIVE
  To determine the effect of daily acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 (HSV-2) in a randomised placebo-controlled trial among rural Zimbabwean sex workers.
  
  
  METHODS
  214 women were recruited and tested for HIV-1 and HSV-2 antibodies, HIV plasma viral load, CD4 lymphocyte count and genital swabs for qualitative detection of HIV-1 and HSV-2 genital shedding. Women were randomly assigned to acyclovir 400 mg twice a day for 12 weeks or matching placebo and were followed weekly to detect HIV-1 or HSV-2 genital shedding. Shedding analyses were only undertaken on 125 women co-infected with HSV-2 and HIV-1. Data were analysed using logistic regression, with random effects modelling used to account for repeated measurements on the same women.
  
  
  RESULTS
  All women were randomly assigned to acyclovir or placebo; 125 of whom were co-infected with HIV-1 and HSV-2. 69 women were randomly assigned to acyclovir and 56 to placebo. Although twice daily acyclovir reduced rates of HSV-2 genital shedding, (adjusted odds ratio (AOR) 0.24; 95% CI 0.12 to 0.48; less than p<0.001), it had no effect on the proportion of visits at which HIV-1 shedding was detected (AOR 1.08; 95% CI 0.48 to 2.42; p = 0.9). Adherence varied between participants but even when adherence was high (as determined by pill count and extent of HSV-2 suppression) HIV-1 shedding was not reduced.
  
  
  CONCLUSIONS
  Among these HIV-1 and HSV-2-seropositive women, suppressive acyclovir therapy had no effect on the rate of HIV genital shedding despite a reduction in genital HSV-2. Treatment adherence and its measurement clearly affect the interpretation of these results.
authors.affiliation: Centre for Sexual Health and HIV Research, Royal Free and University College Medical School, University College London, Mortimer Market Centre, off Capper Street, London WC1E 6AU, UK. frances@uz-ucsf.co.zw
authors.forename: F M
authors.initials: FM
authors.lastname: Cowan
authors.forename: S J
authors.initials: SJ
authors.lastname: Pascoe
authors.forename: K L
authors.initials: KL
authors.lastname: Barlow
authors.forename: L F
authors.initials: LF
authors.lastname: Langhaug
authors.forename: S
authors.initials: S
authors.lastname: Jaffar
authors.forename: J W
authors.initials: JW
authors.lastname: Hargrove
authors.forename: N J
authors.initials: NJ
authors.lastname: Robinson
authors.forename: M T
authors.initials: MT
authors.lastname: Bassett
authors.forename: D
authors.initials: D
authors.lastname: Wilson
authors.forename: D W G
authors.initials: DW
authors.lastname: Brown
authors.forename: R J
authors.initials: RJ
authors.lastname: Hayes
mesh_terms: D000212:Acyclovir / Q000627:therapeutic use*; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006558:Herpes Genitalis / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000502:physiology*; D006801:Humans; D010349:Patient Compliance; D012423:Rural Health; D011477:Sex Work; D019562:Viral Load; D017201:Virus Shedding; D015030:Zimbabwe
chemical_list: D000998:Antiviral Agents; D000212:Acyclovir