Two phase-3 microbicide studies stopped early due to safety concerns

Issue: March 2007

Two phase-3 clinical trials examining the potential protective effects of an anti-HIV/AIDS microbicide have been stopped early due to safety concerns.

The trials, conducted in India and several nations in Africa, were testing Ushercell (Polydex Pharmaceuticals), a vaginal gel containing 6% cellulose sulfate. Early results suggested that the microbicide may not help protect women against contracting HIV. In fact, some data suggested the microbicide might actually increase the risk of transmission.

This is a setback for the development of microbicides, which have been heavily promoted as a potential breakthrough in helping to reduce the risk of HIV transmission among women. Microbicides are considered a particularly important potential tool for women whose sexual partners may not be willing to use a condom.

The microbicide had been studied for years before the phase-3 trials began. All earlier research indicated that the microbicide was safe and should proceed to phase-3 trials.

Concerns of risk

One of the microbicide studies, directed by CONRAD, a reproductive heath research organization, was conducted in South Africa, Benin, Uganda and India and involved 1,500 women. The study began in July 2005 and was halted in January 2007 after the Independent Data Monitoring Committee, an independent scientific advisory group that was overseeing the trial, found that women who used the microbicide may be at an increased risk for contracting HIV.

“It was our hope that this product would have helped women in protecting themselves from HIV,” Lut Van Damme, MD, an investigator of the CONRAD trial, said in a press release. “While the findings are unexpected and disappointing, we will learn scientifically important information from this trial that will inform future HIV prevention research.”

The second trial, conducted in Nigeria by Family Health International, was also stopped based on data from the CONRAD trial. Although there was no evidence that women who used the microbicide had an increased risk of contracting HIV in this trial, there was also no evidence that the microbicide offered any protective effects. Based on these initial results and the results from the CONRAD trial, the researchers stopped this study early as a precautionary measure.

Health advocates respond

Following the reports regarding the end of the two trials, health advocates and scientists from throughout the world expressed their surprise and disappointment. “Of course we wish the results had been different, but learning what does not work can be just as important to progress as learning what does work,” Lori Heise, director of the Global Campaign for Microbicides, said in a press release. “It is also reassuring that the independent Data Safety and Monitoring Committees, put in place to identify problems early on in a trial, appear to have worked well. Advocates have been instrumental in pushing for extra mechanisms to help protect participant safety.”

There are several trials examining the use of other microbicides currently underway elsewhere in the world.

PERSPECTIVE

This is a major disappointment, as vaginal microbicides seemed to offer a convenient way for women in many less developed countries to help reduce the risk of HIV transmission.

– Theodore C. Eickhoff, MD

Chief Medical Editor