MONTREAL, CANADA--Trials of microbicide gels to protect women against HIV infection have a perfect record--not one of them has worked, and some were even harmful. But now a large international study has ended that curse, although the gel's benefits appear to be modest and require confirmation.
As reported here today at the 16th Conference on Retroviruses and Opportunistic Infections, the study showed that a microbicide called PRO 2000 reduced the risk of HIV infection by 30%. The finding did not quite reach statistical significance, however, stressed the head of the study, epidemiologist Salim Abdool Karim of the Centre for the AIDS Programme of Research in Durban, South Africa.
But given the disastrous track record for vaginal microbicides, the field is celebrating this as a landmark advance. At the end of Karim's talk, several researchers praised the findings, marginal as they are. "This is a very important study," said Sten Vermund, an epidemiologist at the University of Alabama, Birmingham. "Finally, there's been a signal in the microbicide field, and that's a thrilling event."
The 3-year trial, which cost $90 million and was funded by the U.S. National Institutes of Allergy and Infectious Diseases, took place in four sub-Saharan African countries and the United States. Before intercourse, the 3000 participants used PRO 2000, another experimental microbicide called BufferGel, an inert placebo gel, or no gel. The 750 women in the PRO 2000 arm of the study had 36 HIV infections, whereas the other groups had between 51 and 54 infections each. Karim said they deemed the placebo gel the best control, and PRO 2000 showed that it was 30% more effective, noting that it would have reached statistical significance at 33%. Karim emphasized that married women in sub-Saharan Africa often do not have the option of using condoms. "In that population, 30% protection to me is a big difference."
PRO 2000 has a negative charge, and researchers hoped it would bind to HIV surface proteins that have a positive charge, blocking the virus's ability to infect cells. Many researchers have given up on this idea and on similar microbicides like BufferGel that attempt to stop HIV by so-called nonspecific mechanisms; instead, they are placing their bets on products that incorporate anti-HIV drugs. But these results are making them do a double take. "It's exciting to find a positive trend," says virologist Robert Grant, a researcher at the University of California, San Francisco, who co-authored an article in Science last year that all but dismissed nonspecific approaches. "I was surprised."
Researchers now are eager to learn the results of a larger trial of PRO 2000 that is under way in four sub-Saharan African countries and is slated to conclude later this year. However, if this study validates the 30% efficacy by reaching statistical significance, it creates a dilemma, researchers say. What if some women don't encourage partners to use condoms because they believe the gel will prevent HIV transmission? "Before a decision will be made about bringing this to market, we'd have to do a lot of thinking," said Sharon Hillier, a microbiologist at the University of Pittsburgh in Pennsylvania who heads the network that organized the original trial. Regardless of PRO 2000's fate, the findings have lifted the field's spirits, increasing the hope that microbicide gels with anti-HIV drugs will achieve indisputable, high levels of protection.