AIDS prevention gel experiments might hide drug-resistance risk

Experiments with AIDS-preventing gels may hide the potential risk that they'll create drug-resistant forms of the virus in patients, scientists said in a study.

HIV mutates quickly to overcome a drug when it's used alone in an infected person. Prevention trials that halt the use of the gels, called microbicides, in women who have become infected with the AIDS virus might allow risky products to enter the market, the international team of researchers said today in the Proceedings of the National Academy of Sciences journal.

Some gels contain a dose of a single antiviral drug that may kill the AIDS virus, called HIV, before it can begin its attack on the body. Trials that remove infected women probably won't show the risk that a microbicide will contribute to resistance, said Sally Blower, a professor of biomathematics at the University of California, Los Angeles, Geffen School of Medicine, who helped write the study.

"Ethically, it's a good strategy to take infected women out of the microbicide trials," Blower said in a telephone interview. "But when you use microbicides as a public health intervention, some women will get infected without being diagnosed, and will probably develop resistance to the drug in the microbicide."

Scientists are testing a gel containing tenofovir, the active ingredient in Gilead Sciences Inc.'s Viread AIDS drug, as a preventative, the study said. The International Partnership for Microbicides also has planned trails of a microbicide containing dapivirine, an experimental drug developed by Johnson & Johnson's Tibotec unit.

AIDS has killed more than 25 million people in the quarter-century since it was identified, and today HIV infects more than 33 million people worldwide, according to UN AIDS, a United Nations health agency. More than half of the estimated 2.5 million annual new infections are in women, according to UN AIDS. Men can reduce their risk of catching AIDS from women by more than 50 percent by getting circumcised, recent studies have shown. Condom use can also stop transmission. However, without a vaccine, there are few ways for women to protect themselves from the lethal infection, the study said.

The findings in the study from Blower, along with colleagues in Canada and the U.K., are particularly "disturbing" for poor countries where there are few options for treatment of HIV, said Rowena Johnston, director of research for AMFAR, the Foundation for AIDS Research, in New York. People whose HIV infections don't respond to doctors' first choices may have few affordable drugs, if any, to turn to, she said.

The study, which was conducted using a computerized replication of a prevention trial, adds to a series of setbacks for microbicides. Carraguard, an HIV prevention gel made from seaweed, failed in February after a three-year trial in more than 6,000 women. Last year, tests of a product called Ushercell were halted after more of the women who used it became infected with HIV than those who got a placebo.

"Finding an effective microbicide is going to be challenging enough," Johnston said in a telephone interview. "We don't want to compound that with the possibility of creating drug resistance." Scientists may switch to experimenting with microbicides containing drug combinations that won't encourage the development of resistant strains, she said.

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