title: Impact of aciclovir on genital and plasma HIV-1 RNA in HSV-2/HIV-1 co-infected women: a randomized placebo-controlled trial in South Africa.
abstract: BACKGROUND
  Several studies suggest that herpes simplex virus type 2 (HSV-2) may enhance HIV-1 transmission and disease progression.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled trial of aciclovir 400 mg twice daily for 3 months in 300 HSV-2/HIV-1 co-infected women not yet on highly active antiretroviral therapy (HAART). Participants were evaluated prerandomization and at monthly visits for 3 months. Primary outcomes were the detection and quantity of genital HIV-1 RNA at the month 3 (M3) visit. Analyses were also undertaken using data from all visits. The treatment effects on plasma HIV-1 RNA, CD4 cell count and genital HSV-2 DNA were also assessed.
  
  
  RESULTS
  At M3 fewer women had detectable genital HIV in the aciclovir group compared to placebo, but this was not significant [61/132 (46%) vs. 71/137 (52%), risk ratio (RR) 0.89, 95% confidence interval (CI) 0.70-1.14; P = 0.36]. There was also little difference in quantity of HIV-1 RNA among shedders (+0.13 log10 copies/ml, 95% CI -0.14 to 0.39) at M3. However, aciclovir significantly decreased the frequency of HIV-1 shedding over all visits [adjusted odds ratio (OR) 0.57, 95% CI 0.36-0.89]. Significant reductions in M3 plasma HIV-1 RNA (-0.34 log10 copies/ml, 95% CI 0.15-0.54), genital HSV-2 DNA (8 vs. 20%, RR 0.37, 95% CI 0.19-0.73) and genital ulceration (8 vs. 18%, RR 0.43, 95% CI 0.22-0.84) were observed in the aciclovir group.
  
  
  CONCLUSIONS
  HSV-2 suppressive therapy, by reducing HIV-1 plasma viral load and altering the pattern of genital HIV-1 shedding, may contribute to the reduction in sexual transmission of HIV-1 and may delay the requirement for HAART initiation.
authors.affiliation: Reproductive Health & HIV Research Unit, University of Witwatersrand, Johannesburg, Republic of South Africa. sdelany@rhru.co.za
authors.forename: Sinéad
authors.initials: S
authors.lastname: Delany
authors.forename: Nonkululeko
authors.initials: N
authors.lastname: Mlaba
authors.forename: Tim
authors.initials: T
authors.lastname: Clayton
authors.forename: Godspower
authors.initials: G
authors.lastname: Akpomiemie
authors.forename: Alexio
authors.initials: A
authors.lastname: Capovilla
authors.forename: Jerome
authors.initials: J
authors.lastname: Legoff
authors.forename: Laurent
authors.initials: L
authors.lastname: Belec
authors.forename: Wendy
authors.initials: W
authors.lastname: Stevens
authors.forename: Helen
authors.initials: H
authors.lastname: Rees
authors.forename: Philippe
authors.initials: P
authors.lastname: Mayaud
mesh_terms: D000212:Acyclovir / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002584:Cervix Uteri / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006558:Herpes Genitalis / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis / Q000097:blood; D012725:Sexual Behavior; D013048:Specimen Handling / Q000379:methods; D016896:Treatment Outcome; D014621:Vagina / Q000821:virology; D017201:Virus Shedding / Q000187:drug effects; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D000212:Acyclovir