Microbicide Trials Halted in Africa, India Because of Possible Increased Risk of HIV Transmission
Arlington, Va.-based Conrad on Wednesday announced that it has halted Phase III trials of the microbicide Ushercell, also known as cellulose sulfate, in Africa and India after an independent scientific committee during a routine check found an increased risk of HIV transmission among women who used cellulose sulfate compared with women who used a placebo gel, the New York Times reports (Altman, New York Times, 2/1). Microbicides include a range of products -- such as gels, films and sponges -- that could help prevent the sexual transmission of HIV and other infections (Kaiser Daily HIV/AIDS Report, 12/13/06). According to the Wall Street Journal, the trials involved about 1,300 women in Benin, India, South Africa and Uganda. Thirty-five women in both the cellulose sulfate and placebo groups became HIV-positive during the trial, the Journal reports. Although a breakdown of incidence rates for each group is not available, there were more new cases in the cellulose sulfate group, the Journal reports (Chase, Wall Street Journal, 2/1). Final numbers are expected in March, according to a Conrad spokesperson. A separate study of Ushercell involving 1,700 participants in Nigeria and conducted by Triangle Park, N.C.-based Family Health International also was halted in response to the findings of the Conrad study. According to the Times, the FHI study had found neither an increased risk of HIV transmission nor a benefit in preventing transmission of the virus. Both the Conrad and FHI studies were funded with $20 million from the Bill & Melinda Gates Foundation and USAID (New York Times, 2/1). According to the Journal, it is still unknown if researchers will be able to develop a "chemical that is tough enough to repel or kill HIV, yet gentle enough to spare the female genital tract from corrosive chemical effects that have the effect of favoring infection." However, the Journal reports that it is "premature to declare defeat" with the World Health Organization and UNAIDS saying that there are three other Phase III microbicide trials currently underway. The Population Council is conducting a study of Carraguard in South Africa, with results expected by the end of the year. The U.K. Medical Research Council is conducting a study of PRO 2000 in South Africa, Tanzania and Uganda, with results expected by 2009. In addition, NIH is conducting trials of PRO 2000 and BufferGel in Malawi, South Africa, Zambia and Zimbabwe, with results expected in 2008 (Wall Street Journal, 2/1).
According to researchers, the findings are surprising because 11 smaller trials involving more than 500 women conducted since 1999 have found that cellulose sulfate is safe and effective against HIV transmission in laboratory tests (New York Times, 2/1). "This development saddens everyone," Zeda Rosenberg, CEO of the International Partnership for Microbicides, said, adding, "We cannot let it paralyze us. Globally, 17.7 women are living with HIV, and thousands more are infected every day. Prevention is the only way out of this epidemic." Nick Hellmann, interim director of HIV/AIDS and tuberculosis at the Gates Foundation, called the results a "disappointment" but said that drug development is a "long, tortuous road." He added that "we have to proceed, stay the course and learn more lessons about what is required for the optimum microbicide product" (Wall Street Journal, 2/1). Lori Heise, director of the Global Campaign for Microbicides, said that "we wish the results had been different, but learning what doesn't work can be just as important to progress as learning what does work." Mitchell Warren, director of the AIDS Vaccine Advocacy Coalition, said, "Each trial result is a puzzle piece, and together they make up the complex picture that will show us how to develop successful new HIV prevention tools" (Global Campaign for Microbicides release, 1/31). Pedro Cahn, president of the International AIDS Society, said, "While extremely disappointing, this setback is also an opportunity to learn why some women who used Ushercell were found to be at increased risk of HIV infection. This will strengthen future microbicide research and increase our overall knowledge of how such compounds work" (IAS release, 2/1).