The Disappointing Data Behind the Latest Failed Microbicide

Summary and Comment |
July 30, 2008

The Disappointing Data Behind the Latest Failed Microbicide

  1. Abigail Zuger, MD

Intravaginal cellulose sulfate gel did nothing to prevent HIV acquisition.

  1. Abigail Zuger, MD

The search for an effective anti-HIV vaginal microbicide has yielded as many disappointments as has the search for an effective vaccine. Eighteen months ago, a large trial of intravaginal cellulose sulfate gel was stopped prematurely because of data suggesting that the product enhanced HIV acquisition (AIDS Clin Care Sep 10 2007). The full details of the study have now been published.

Almost 1400 sexually active HIV-negative women in Africa and India (median age, 29) were randomized to use either cellulose sulfate or placebo gel in the hour preceding vaginal intercourse. The median number of male partners in the 3 months before screening was 10, with a median of four episodes of vaginal intercourse reported for the week before screening.

The study was stopped after an interim analysis uncovered a significantly higher rate of new HIV infections in the cellulose sulfate group (24 vs. 11; hazard ratio, 2.2). The final analysis, however, included 6 additional infections diagnosed right before the study ended, for a tally of 25 infections in the cellulose-sulfate group and 16 in the placebo group, a nonsignificant difference.

Rates of gonorrhea and chlamydia were similar between the study groups, although cellulose sulfate has in vitro activity against both Neisseria gonorrhoeae and Chlamydia trachomatis. Clinical data suggest that the gel is also an effective contraceptive, but pregnancy rates were similar between groups. Although study participants reported high rates of both condom use and gel use (96% and 87% of intercourse acts, respectively), rates fell during intercourse with primary partners, and when condoms were not used, gel was used less than half the time.

Comment

Cellulose sulfate gel clearly has no role in HIV prevention, but why not? The authors suggest a combination of low adherence to the product, particularly during risky, condom-free encounters, and the possibility that the cellulose gel did indeed enhance HIV acquisition with cumulative use. They wonder whether future microbicide research should not be done in two cohorts of women, “one with high coital frequency, to assess potential negative effects of high product exposure, and one with low coital frequency, to assess effectiveness. . . .” Like the search for a vaccine, this arena of HIV prevention gets only more tangled and complex.

Citation(s):

Your Comment

(will not be published)

Filtered HTML

  • Allowed HTML tags: <a> <em> <strong> <cite> <blockquote> <code> <ul> <ol> <li> <dl> <dt> <dd>
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Do you have any conflict of interest to disclose?
CAPTCHA
This question is for testing whether you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

* Required

Reader comments are intended to encourage lively discussion of clinical topics with your peers in the medical community. We ask that you keep your remarks to a reasonable length, and we reserve the right to withhold publication of remarks that do not meet this standard.

PRIVACY: We will not use your email address, submitted for a comment, for any other purpose nor sell, rent, or share your e-mail address with any third parties. Please see our Privacy Policy.