A microbicide gel designed to block the transmission of the AIDS virus to women has failed the largest clinical trial to date, a bitterly disappointing finding for researchers that likely spells the end of research on this form of such products. The findings announced Monday by England's Medical Research Council represent a major letdown because results from a smaller study presented in February at a major AIDS conference suggested that the microbicide could block transmission of HIV by 30%, although the results were not statistically significant. Researchers are now turning their attention to microbicides containing anti-HIV drugs.
Short of a vaccine, vaginal microbicides are considered one of the most promising ways to prevent transmission of the virus to women. Such an approach would give women a great deal of control over their health when marital or other sexual partners refuse to use condoms. The idea is that the microbicide will tie up or kill the virus in the vagina before it can penetrate the tissues and infect the woman. Such a product must not be unpleasantly messy or sticky and should be able to block the virus without impeding the much larger sperm.
The trial involved a microbicide called PRO 2000 manufactured by Endo Pharmaceuticals of Chadds Ford, Penn. Its active ingredient is a polymer of naphthalene sulfonate designed to bind to receptors on the surface of HIV, preventing it from penetrating vaginal tissue. Tests in the laboratory showed that it binds strongly to the virus, suggesting that it would be effective in actual use.
The trial, sponsored by the London-based Microbicides Development Programme--a coalition of 16 European and African research institutions--involved 9,385 African women in four countries. The women were given either a placebo gel, a gel containing 0.5% of PRO 2000 or a gel containing 2% PRO 2000. The gels were to be used before and after sex. The women were also counseled to use condoms whenever possible and on other ways to minimize the risk of infection. The women reported that they liked the gel and many were disappointed when they had to stop using it.
The arm of the trial using the higher concentration was halted in February 2008 when it became clear that the microbicide would not work at that concentration.
There were 130 HIV infections in the 3,156 women who received the 0.5% gel and 123 in the 3,112 women receiving the placebo gel during the 12 to 24 months of follow-up. That works out to a rate of 4.5 infections per 100 women-years in the group receiving PRO 2000 and 4.3 in the placebo group.
"This result is disheartening, particularly in light of the results of a smaller trial sponsored by the U.S. National Institutes of Health," the study's chief investigator, Dr. Sheena McCormack of the Medical Research Council, said in a statement. "Nevertheless, we know that this is an important result and it clearly shows the need to undertake trials which are large enough to provide definitive evidence for whether a product works."
-- Thomas H. Maugh II