http://seattlepi.nwsource.com/health/351684_microbicide18.html

"Carraguard was shown to be safe but not effective at preventing HIV transmission," said Dr. Khatija Ahmed, the lead scientist on the three-year clinical trial conducted by the Population Council, an international research organization focused on reproductive health.

Carraguard, a seaweed-based gel that blocks HIV infection of cells in lab tests, had been considered the most promising of several experimental microbicidal vaginal gels or creams intended to reduce a woman's risk of HIV.

The study, which lasted three years and was the only one so far to get to the final phase of testing, ended with 134 new HIV infections among women who used the microbicide and 151 infections among women given placebo gel. Statistically, considered within the 4,244 women who completed the study, this was regarded as no difference.

"We're all disappointed, but we're going to learn from this," said Lori Heise, director of the Global Campaign for Microbicides, based in Washington, D.C., and operated by Seattle-based PATH, the Program for Appropriate Technology in Health.

More than 15 years ago, Heise and Dr. Chris Elias, now president at PATH, worked at the Population Council and actually coined the term "microbicide." The goal was to promote the concept of a South African epidemiologist, Zena Stein, of finding a simple, inexpensive anti-HIV vaginal cream that could be used by women to protect against infection.

Worldwide, by far most new HIV infections today are in women. UNAIDS, the United Nations Joint Program on HIV/AIDS, has estimated that women in sub-Saharan Africa are anywhere from three to six times more likely to become infected by HIV than men due to a greater inability to adequately protect against infection during sexual intercourse.

Carraguard, developed by the Population Council from a seaweed derivative known as carrageenan used in ice cream and cosmetics, had been considered a top contender. Studies of two other experimental anti-HIV microbicides, (a spermicide called nonoxynol-9 and another one using the chemical cellulose sulfate), had to be halted due to safety concerns when it appeared test subjects had higher rates of HIV infection.

Some wonder if further analysis of the trial data may even show it wasn't so much Carraguard that failed to protect against HIV as it was the inability of study participants to use it consistently.

The Population Council said the Carraguard study participants "self-reported" using the gel in 44.1 percent of their sex acts. Only 10 percent of the women said they used the gels 100 percent of the time and only 20 percent used the gels three-quarters of the time.

"It could still turn out, upon further analysis among those who used it more consistently, that there was a protective effect," said Dr. Henry Gabelnick, executive director of CONRAD, a reproductive health and HIV research organization based in Arlington, Va., that led the cellulose sulfate microbicide study.

Heise, however, said that to get an anti-HIV microbicide approved by regulators and put into wide distribution, they would likely need much more than that kind of parsed evidence anyway.

"This is an entirely new class of (medical) product," she said. A more important lesson to take away from this trial is to conduct future microbicide trials with much greater attention to and emphasis on maximizing subject participation, she said.

"What we haven't done well is really focus on the behavioral side of this equation," she said.

Barbara Friedland, behavioral coordinator on this study and an AIDS expert with the Population Council, agreed with Heise and Gabelnick. Friedland said it is possible they could have seen different results had the rate of consistent use of Carraguard been higher. "But it's tricky. Everyone struggles with adherence (to consistent use) on these kind of trials. Everybody tries to improve both adherence and our ability to measure it."

The Population Council plans to continue testing Carraguard, next time in combination with an experimental anti-HIV drug known as MIV-150. This drug, initially abandoned by a drug maker because it is not absorbed when taken internally, nevertheless fights the AIDS virus on contact in lab cultures.