title: The safety of candidate vaginal microbicides since nonoxynol-9: a systematic review of published studies.
abstract: OBJECTIVE
  To gain a greater understanding of published safety data for candidate vaginal microbicides.
  
  
  METHODS
  A systematic review of human safety trials of candidate vaginal microbicides - agents designed to protect women against HIV and other sexually transmitted infections.
  
  
  METHODS
  Trials were published in peer-reviewed journals, and publication cut-off was August week 4, 2008. Trials of nonoxynol-9 were excluded, as were trials without a control group, trials that enrolled only male participants or reported on the investigation of a product for the treatment of a genital infection.
  
  
  RESULTS
  Twenty-one trials of 11 products, involving 1465 women, satisfied review criteria. Most trials reported on genital epithelial findings and urogenital symptoms and a number reported a range of other local and systemic toxicity endpoints. Trials were generally of short duration (2 weeks or less) with small sample sizes. There were few findings of significant difference between women in active and control arms. Among the products assessed in more than one study, there were significantly more genital findings with intact epithelium in recipients of PRO2000 [relative risk (RR) 1.68, 95% confidence interval (CI) 1.08-2.60] and a lower incidence of bacterial vaginosis in dextrin sulphate recipients (RR 0.61, 95% CI 0.42-0.88). CIs were generally very wide, and most studies were unable to exclude differences of a substantial magnitude between treated and control women.
  
  
  CONCLUSIONS
  Larger and longer safety studies are necessary to detect clinically important toxicities, including those that indicate a potential increase in HIV risk, and provide assurance that agents are ready for large-scale effectiveness trials.
authors.affiliation: University of New South Wales, Sydney, Australia.
authors.forename: I Mary
authors.initials: IM
authors.lastname: Poynten
authors.forename: Iona Y
authors.initials: IY
authors.lastname: Millwood
authors.forename: Michael O
authors.initials: MO
authors.lastname: Falster
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Law
authors.forename: David N
authors.initials: DN
authors.lastname: Andresen
authors.forename: Lut
authors.initials: L
authors.lastname: Van Damme
authors.forename: John M
authors.initials: JM
authors.lastname: Kaldor
mesh_terms: D000282:Administration, Intravaginal; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005831:Genital Diseases, Female / Q000139:chemically induced; D015658:HIV Infections / Q000517:prevention & control; D006801:Humans; D017137:Nonoxynol / Q000008:administration & dosage / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012749:Sexually Transmitted Diseases / Q000517:prevention & control*; D016585:Vaginosis, Bacterial / Q000139:chemically induced
chemical_list: D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D017137:Nonoxynol