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The Disappointing Data Behind the Latest Failed Microbicide

Intravaginal cellulose sulfate gel did nothing to prevent HIV acquisition.

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.

— Abigail Zuger, MD

Published in Journal Watch HIV/AIDS Clinical Care July 30, 2008

Citation(s):

Van Damme L et al. Lack of effectiveness of cellulose sulfate gel for the prevention of vaginal HIV transmission. N Engl J Med 2008 Jul 31; 359:463.

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