title: A dose-ranging phase I study of dextrin sulphate, a vaginal microbicide, in HIV-negative and HIV-positive female volunteers.
abstract: METHODS
  This phase I dose-ranging study of 2 weeks of twice-daily dextrin sulphate (DS), a sulphated polymer with in vitro activity against HIV, was designed in 2 parts. Part A was a randomized, placebo-controlled, double-blind, 3-arm trial (DS4%, DS1%, placebo) in HIV-negative women. In part B, HIV-positive women received DS4% and HIV-negative women were randomized to DS4% or no gel.
  
  
  RESULTS
  One hundred women were enrolled from 2 sites (London and Antwerp): DS4% (n = 50, 20 of whom were HIV-positive), DS1% (n = 20), placebo (n = 10) and no gel (n = 20). There were no withdrawals related to adverse events and no cases of epithelial disruption. Spotting was reported by 24 women and numbers were significantly higher in all the gel groups (23 of 80), including placebo, compared with no gel (one of 20) (Fisher exact test P = 0.037). There was no evidence of a dose effect. Safety tests showed no evidence of systemic absorption.
  
  
  CONCLUSIONS
  Although there was no clear explanation for the spotting, DS4% was well tolerated. It was decided to proceed with DS4% in an expanded safety study in Africa but to restrict entry to low-risk HIV-negative women, include a no-gel group, and monitor intermenstrual bleeding closely.
authors.affiliation: Medical Research Council Clinical Trials Unit, London, UK. smccormack@ctu.mrc.ac.uk
authors.forename: Sheena
authors.initials: S
authors.lastname: McCormack
authors.forename: Vicky
authors.initials: V
authors.lastname: Jespers
authors.forename: Naomi
authors.initials: N
authors.lastname: Low-Beer
authors.forename: Rhian
authors.initials: R
authors.lastname: Gabe
authors.forename: Nicola
authors.initials: N
authors.lastname: Kaganson
authors.forename: Alan
authors.initials: A
authors.lastname: Chapman
authors.forename: Andrew
authors.initials: A
authors.lastname: Nunn
authors.forename: Charles
authors.initials: C
authors.lastname: Lacey
authors.forename: Lut
authors.initials: L
authors.lastname: Van Damme
mesh_terms: D000282:Administration, Intravaginal; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007560:Cote d'Ivoire; D003912:Dextrins / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005782:Gels / Q000008:administration & dosage / Q000009:adverse effects; D006678:HIV; D018023:HIV Seronegativity; D006679:HIV Seropositivity / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D012725:Sexual Behavior; D016896:Treatment Outcome; D014454:Uganda
chemical_list: D000890:Anti-Infective Agents; D003912:Dextrins; D005782:Gels; C091377:dextrin 2-sulfate