By David Brown
Washington Post Staff Writer
Tuesday, February 10, 2009
AIDS researchers who were gathered in Montreal yesterday heard encouraging results from studies of three strategies for preventing HIV infection using pharmaceuticals, particularly in women.
Two experiments in monkeys showed that antiretroviral (ARV) drugs, given by mouth or by vaginal gel, were highly effective in blocking infection by the virus that causes AIDS.
A third study, in 3,100 women in the United States and Africa, showed a small amount of protection from a vaginal gel that acts by binding up the AIDS virus and preventing it from invading cells.
Many experts believe that, short of a vaccine, a virus-blocking substance that could be inserted in the vagina or rectum before sexual activity would be the most important tool in fighting the AIDS pandemic. Numerous topical microbicides have been tried, but none have worked, and two have actually increased the risk of infection.
"The field of microbicide gels is now moving into a new generation," said Walid Heneine, a virologist at the U.S. Centers for Disease Control and Prevention, who led one of the monkey studies.
Microbicides can be applied without the knowledge of sexual partners. They are seen as being especially important in cultures where the subservient status of women makes it difficult for them to insist on abstinence or condom use, the two proven methods of preventing infection through sexual contact. In sub-Saharan Africa, nearly 60 percent of HIV-positive people are women.
The gel used in the human study reduced the risk of infection by 30 percent over the course of about two years, an effect that did not reach the level of statistical significance. The women -- from the United States, South Africa, Malawi, Zambia and Zimbabwe -- also used condoms in about three-quarters of their sexual encounters.
A study by British and African researchers that is testing the same microbicide in 9,400 women may have interim results later this year.
Although this result was marginal, the substance, called PRO 2000/5, may ultimately prove useful to women who are monogamous, are married to high-risk men and do not want to use condoms because they want to conceive, the lead researcher said.
"This could be a niche product for a group of women who have no other option," said Salim Abdool Karim of Durban, South Africa. He spoke at a news conference at the 16th Conference on Retroviruses and Opportunistic Infections, the annual mid-winter AIDS meeting in North America.
In the first monkey study, researchers gave rhesus macaques oral doses of a compound containing two ARV drugs, tenofovir and emtricitabine (which is sold under the name Truvada). The medicine was administered at different intervals, both before and after the animals were rectally exposed to the AIDS virus once a week for three months.
When the first dose was given either one or three days before contact with the virus, five out of six animals were protected. When it was given seven days before exposure, four in six animals were protected. When the dose was two hours before exposure, however, only three in six were protected.
Of 27 untreated animals, 26 became infected after an average of two exposures.
Tenofovir has a very long active life inside the body. But two hours appears to be not enough time for it to be absorbed and carried into the cells of the immune system, which are HIV's target, said J. Gerardo García-Lerma, the CDC virologist who led the study.
There are seven studies in people testing either Truvada or tenofovir alone as an HIV-prevention pill. In each of the experiments, which are enrolling a total of 18,000 volunteers in the United States, Kenya, Uganda, Botswana and Thailand, the drugs are administered every day. The monkey study suggests that intermittent dosing might work, too.
In the other monkey study, researchers used vaginal gels containing either both drugs or tenofovir alone. The gel was applied half an hour before twice-weekly vaginal exposure to the virus.
The six monkeys that received the two-drug gel were all protected, as were the six who got the tenofovir-only gel. Of 11 monkeys in a control group, 10 became infected after an average of four exposures to the virus.
Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, said he was buoyed by the results of the animal experiments and not entirely discouraged by the human results.
"In such a sea of disappointment as microbicide research, a study that is even a little encouraging is something to notice," he said.