title: Lack of effectiveness of cellulose sulfate gel for the prevention of vaginal HIV transmission.
abstract: BACKGROUND
  Women make up more than 50% of adults living with human immunodeficiency virus (HIV) infection or the acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa. Thus, female-initiated HIV prevention methods are urgently needed.
  
  
  METHODS
  We performed a randomized, double-blind, placebo-controlled trial of cellulose sulfate, an HIV-entry inhibitor formulated as a vaginal gel, involving women at high risk for HIV infection at three African and two Indian sites. The primary end point was newly acquired infection with HIV type 1 or 2. The secondary end point was newly acquired gonococcal or chlamydial infection. The primary analysis was based on a log-rank test of no difference in the distribution of time to HIV infection, stratified according to site.
  
  
  RESULTS
  A total of 1398 women were enrolled and randomly assigned to receive cellulose sulfate gel (706 participants) or placebo (692 participants) and had follow-up HIV test data. There were 41 newly acquired HIV infections, 25 in the cellulose sulfate group and 16 in the placebo group, with an estimated hazard ratio of infection for the cellulose sulfate group of 1.61 (P=0.13). This result, which is not significant, is in contrast to the interim finding that led to the trial being stopped prematurely (hazard ratio, 2.02 [corrected]; P=0.05 [corrected]) and the suggestive result of a preplanned secondary (adherence-based) analysis (hazard ratio, 2.02; P=0.05). No significant effect of cellulose sulfate as compared with placebo was found on the risk of gonorrheal infection (hazard ratio, 1.10; 95% confidence interval [CI], 0.74 to 1.62) or chlamydial infection (hazard ratio, 0.71; 95% CI, 0.47 to 1.08).
  
  
  CONCLUSIONS
  Cellulose sulfate did not prevent HIV infection and may have increased the risk of HIV acquisition. (ClinicalTrials.gov number, NCT00153777; and Current Controlled Trials number, ISRCTN95638385.)
authors.affiliation: CONRAD, Arlington, VA, USA. lvandamme@fhi.org
authors.forename: Lut
authors.initials: L
authors.lastname: Van Damme
authors.forename: Roshini
authors.initials: R
authors.lastname: Govinden
authors.forename: Florence M
authors.initials: FM
authors.lastname: Mirembe
authors.forename: Fernand
authors.initials: F
authors.lastname: Guédou
authors.forename: Suniti
authors.initials: S
authors.lastname: Solomon
authors.forename: Marissa L
authors.initials: ML
authors.lastname: Becker
authors.forename: B S
authors.initials: BS
authors.lastname: Pradeep
authors.forename: A K
authors.initials: AK
authors.lastname: Krishnan
authors.forename: Michel
authors.initials: M
authors.lastname: Alary
authors.forename: Bina
authors.initials: B
authors.lastname: Pande
authors.forename: Gita
authors.initials: G
authors.lastname: Ramjee
authors.forename: Jennifer
authors.initials: J
authors.lastname: Deese
authors.forename: Tania
authors.initials: T
authors.lastname: Crucitti
authors.forename: Doug
authors.initials: D
authors.lastname: Taylor
mesh_terms: D000282:Administration, Intravaginal; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002482:Cellulose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D002690:Chlamydia Infections / Q000517:prevention & control / Q000635:transmission; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005782:Gels; D006069:Gonorrhea / Q000517:prevention & control / Q000635:transmission; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D006801:Humans; D053208:Kaplan-Meier Estimate; D010919:Placebos; D012725:Sexual Behavior; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D005782:Gels; D010919:Placebos; D002482:Cellulose; C020254:cellulose sulfate