Tuesday, February 19, 2008
Results of the trial were released Monday afternoon in South Africa, where the study was carried out among 6,200 volunteers living in three regions of the country.
Half the women were assigned the active ingredient, Carraguard, a gel-like substance derived from seaweed; the other half received an inert material of the same look and texture. Laboratory studies had shown that Carraguard, inserted vaginally, could protect against HIV, but the latest test showed it did not work in the real world.
In tests that lasted up to three years, there were 134 infections in the Carraguard group, and 151 in the group that received the placebo - statistically a dead heat.
Researchers will look at possible reasons for the disappointing results, including the failure of the women in the test to use the gel during most of their sexual encounters.
"Carraguard was safe, but not effective against HIV transmission," said Khatija Ahmed, principal investigator for the study.
This was the first major trial of a so-called microbicide to be completed, as earlier or smaller studies of such products had to be halted when evidence emerged that they not only were not working, but may have increased the risk of HIV infection.
Because Carraguard was proved safe, it might be reused in future studies that add antiviral drugs to the gel. "We will be developing the next generation of products using Carraguard as a base," said Robin Maguire, director of product development for the Population Council, a New York nonprofit.
The Population Council carried out the study with financial support from the Bill & Melinda Gates Foundation and the federal government's U.S. Agency for International Development.
All three organizations have pumped millions of dollars into research to find a microbicide. The long-term goal is to develop a gel or cream that could be inserted vaginally or rectally to block HIV infection.
In Africa, where many women have little control over whether their husband or partner will wear a condom, the development of female-controlled HIV-prevention technologies is a high priority that so far has yielded disappointing results.
In 2000, a study among South African prostitutes showed an alarming increase in HIV infections among those assigned to Nonoxynol-9, an already approved contraceptive gel that blocked the AIDS virus in the test tube. But it apparently also irritated vaginal tissues, providing more routes for HIV to invade the bloodstream.
In January 2007, two trials of an experimental microbicide, cellulose sulfate, were abruptly halted in Africa and India after an initial analysis showed it could be increasing the risk of HIV infection.
In July, a three-year African study testing whether simple use of a diaphragm might protect women from HIV found that it did not.
Two weeks ago, a major study exploring whether treating genital herpes infection with a common drug, acyclovir, could also reduce the risk of HIV infection in gay men and African women reported there was no protective effect.
In the Carraguard study, there are already strong indications that it might have failed because the women in the study were not able to use it consistently. Women typically utilized the product once a week, but sometimes up to 10 times a week. But during the course of the experiment, results showed women used it only 44 percent of the time they had sex.
"That overall number is low, and it could have had an impact," said Barbara Friedland, a Population Council researcher who coordinated behavioral studies in the trial.
Female participants in the trial did not know whether they received the active ingredient, Carraguard, or the placebo. Both groups were given condoms and counseled extensively to use them. It will take further analysis of the study results to determine whether patterns of condom use or failure to use the microbicide played any part in the outcome.
Carraguard had been considered a possible microbicide since 1994. Earlier, smaller studies had indicated it was safe, and that women found the feel, scent and texture of the product acceptable.
According to Population Council researcher Maguire, studies showed that Carraguard could withstand storage in the hot environmental conditions found in Africa for at least four years. The organization is now conducting early studies to determine whether Carraguard might work better if it was mixed with an antiviral drug normally used to treat HIV infection.