WASHINGTON, Feb. 1 (UPI) -- Clinical trials of cellulose sulfate, one of the most promising anti-HIV microbicide compounds, have ended in disappointment, researchers announced late Wednesday.
But advocates for microbicides -- gels that can be applied to the vagina to discreetly protect against HIV and other sexually transmitted infections -- say the search must continue.
"This is a setback, but it does not detract from the issue that women still don't have the tools they need to protect themselves from HIV," said Manju Chatani, coordinator of the African Microbicide Advocacy Group, "and African women, especially, urgently need more prevention options."
Microbicides are preferable to condoms, health advocates say, because in gel, cream or foam formulations, they would allow women to protect themselves from infection without the knowledge of their partner, which is necessary secrecy in parts of the world where women have little control of when and how they have sexual intercourse.
Some of the compounds are also not spermicidal, meaning that women could use them even while trying to become pregnant.
Cellulose sulfate, also known as Ushercell, is a cotton-based compound developed by Polydex Pharmaceuticals, based in Toronto.
A phase 3 trial of the compound being conducted on 1,500 women in South Africa, Benin, Uganda and India was abruptly ended by CONRAD, a Virginia-based consortium of government agencies and non-governmental organizations, after women who received the treatment showed a higher risk of HIV infection than women who received a placebo.
A similar trial of the same compound in Nigeria conducted by Family Health International was also shut down, although it did not show the same preliminary results.
The findings in the double-blinded, randomized trial is both unexplained and surprising, researchers said, because earlier trials of 500 individuals in Africa, India and the United States showed that the compound was both safe and effective at preventing HIV transmission.
The Independent Data Monitoring Committee, an independent advisory group of experts overseeing the trial, will conduct a detailed review of the data to better understand the findings and help determine any implications for other microbicide studies, CONRAD said in a statement released to the media.
"I am surprised and disappointed by these findings, given the pre-clinical effectiveness and safety profile of (cellulose sulfate), and its safety profile demonstrated in phase 1 trials," said Jeff Spieler, chief of research in the Office of Population and Reproductive Health at USAID, which partially funds CONRAD.
However, there may still be lessons to be learned from the research, said Lut Van Damme, principal investigator of the CONRAD trial.
"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."
That information could be applied to the development of other compounds. There are currently 60 microbicides in the drug pipeline, including three in phase 3 trials.
"The data are concerning," Kenneth Mayer, professor of medicine and community health at Brown University, told United Press International. Mayer participated in the earlier U.S. trials.
But the results are preliminary and must be examined further, Mayer said. So far, what they show is that the compound was not preventing HIV infection and may have slightly increased the risk.
"We don't know if that's what happened," he said. "We need to determine if that's the case."
The fact that the research and all other tests of the same compound were halted at the slightest hint of a problem shows the commitment to patient safety that researchers have, said Lori Heise, director of the Global Campaign for Microbicides, a non-profit consumer advocacy group.
"The participant protection put in place worked," she told UPI, noting that the trial was stopped after a total of 35 women from the treated group and the control group were infected, and services were put in place to take care of women who contracted the disease during the course of the trial.
What is important now is that trials of other microbicide compounds go forward, she added. "It's hard for people in the United States to understand the situation. In a lot of the settings where the trials are going on, one in three or even one in two of the women who apply for the trial are already infected (with HIV)."
Long-term relationships are the "Achilles heel" of the epidemic for women, Heise said, because they are the context where many women become infected.
The three other products in phase 3 trials, one of which will be completed in March, show promise, she said, but are first-generation products that began development a decade ago. "We're still hopeful about the other three products, but there are a lot more coming behind them."
Researchers are developing better products all the time, said Carl Dieffenbach, acting director of the AIDS division at the National Institute of Allergy and Infectious Diseases.
"We go from here with new products with more specificity for HIV. This product was relatively non-specific," he told UPI.
There are also possibilities in using compounds in combination, Dieffenbach said. "When you get something that works a little bit, you move to combinations. Maybe we should move directly to combinations."
"We have to go forward -- I think that's clear," Heise of the Global Campaign for Microbicides said. "Women need microbicides so desperately we can't let a setback like this derail us."
