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, 2.23; P = 0.02) and the suggestive result of a preplanned secondary (adherencebased)
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.)
