Two phase III clinical trials of cellulose sulphate—a topical microbicide gel being tested for HIV prevention in women—have been halted because preliminary results showed that the compound increased rather than reduced the risk of HIV infection.
The microbicide, a cotton based compound developed under the brand name Ushercell by Polydex Pharmaceuticals, based in Toronto, had shown initial promise and was being tested on 1333 women in South Africa, Benin, Uganda, and India. The study was sponsored by Conrad, a partnership of the Eastern Virginia Medical School and the US Agency for International Development, with funding from the Bill and Melinda Gates Foundation.
Simultaneously, Family Health International halted a second phase III trial of Ushercell on 1800 women in Nigeria. Although this study did not detect an increased HIV risk associated with cellulose sulphate, the decision was made as a precautionary measure, given the preliminary results in the Conrad trial.
Tim Farley, head of microbicide research at the World Health Organization, told the BMJ that preliminary data from the Ushercell trials may be released next month, but he stressed that no one had died as a result of the studies.
Separate phase III trials of three other microbicidal candidates are continuing unaffected, with the first results expected later this year.
Researchers are still unsure why cellulose sulphate was associated with an increased risk of HIV infection. The independent data monitoring committee, an advisory group of experts overseeing the trial, is reviewing the data in detail to understand the findings better and to help determine any implications for other microbicide studies.
Lut Van Damme, principal investigator of the Conrad trial, said, “It was our hope that this product would have helped women in protecting themselves from HIV. While the findings are unexpected and disappointing, we will learn scientifically important information from this trial that will inform future HIV prevention research.”
Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told the BMJ, “The thing that looms to mind first is that the inflammatory irritant effect trumps what the antiviral blocking effect would be. Obviously this is a setback for this particular trial. I think we still need to pursue a variety of other options in the microbicide area … It is unfortunate that this happened but it underscores the importance of doing carefully monitored clinical trials that have a data safety and monitoring board watching it. Clinical trials have setbacks; that's why you do clinical trials.”
Dr Fauci said, “They stopped the trial for reasons of safety, which is the appropriate thing to do. They've got to go back now and look at that data.”
A joint statement by WHO and UNAIDS said, “The need to continue research to find a user-controlled means of preventing HIV infection in women is urgent. Despite the effectiveness and availability of condoms, the HIV epidemic continues to spread and the search for a safe and effective microbicide is a vital part of the effort to stem the spread of the HIV epidemic.”
“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,” said Pedro Cahn, president of the International AIDS Society and director of Fundación Huésped in Buenos Aires, Argentina. “This will strengthen future microbicide research and increase our overall knowledge of how such compounds work.”
“The importance of developing a safe and effective microbicide to protect women from HIV infection cannot be understated,” said Dr Cahn. “We must give women the tools to protect themselves, independent of their partners' actions.”