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Biological Chemistry

Antiretroviral Agents May Help Avoid Infection

by Ann M. Thayer
September 22, 2008 | A version of this story appeared in Volume 86, Issue 38

COVER STORY

Antiretroviral Agents May Help Avoid Infection

A vaccine may be the ultimate way to prevent HIV infection, but it's not the only one. Behavior modification and safe sex practices are two proven means to limit transmission. For high-risk individuals, researchers are exploring medical interventions, such as microbicides and preexposure prophylaxis (PrEP).

In 2007, $226 million was spent on microbicide R&D, according to the HIV Vaccines & Microbicides Resource Tracking Working Group. Some of a dozen microbicides being tested, including gels and creams, create a physical or environmental barrier, while others use antiretroviral drugs to avert HIV.

Unfortunately, several late-stage clinical trials recently failed to yield positive results. To continue the effort the U.S. Agency for International Development awarded $100 million over five years to the Eastern Virginia Medical School, in Norfolk, for work that will include microbicide studies using the HIV drug tenofovir and an agent called UC781.

About $40 million was spent on PrEP in 2007. Several PrEP studies are exploring whether HIV replication and infection can be stopped by giving antiretrovirals to uninfected people. PrEP hasn't been proven to work, but primate studies suggest that certain drugs can protect against exposure to HIV-like viruses. And giving antiretrovirals to mothers and newborns is believed to be a factor in preventing mother-to-child transmission.

In the absence of an effective HIV vaccine, PrEP is considered a promising intervention step to limit the spread of HIV. As of August, the U.S. Centers for Disease Control & Prevention, the National Institutes of Health, and the Bill & Melinda Gates Foundation were supporting four clinical trials of about 11,000 people. The first results are
expected in 2009, and other trials involving 8,000 more people are planned.

Drugmaker Gilead Sciences has contributed its drugs tenofovir and tenofovir plus emtricitabine for the trials. According to CDC, the two already-approved drugs were chosen because they have proven safety profiles and relatively low levels of side effects. In addition, they can be taken just once per day, and viral resistance to them develops slowly.

"There is a lot of excitement around PrEP," says Carl W. Dieffenbach, director of the National Institute of Allergy & Infectious Diseases' Division of AIDS. "And a number of companies are very interested in getting involved." He suggests that the portfolio of drugs used should be broadened but still limited to those drugs that counter HIV before it integrates into the human genome.

"While we work toward a vaccine, we need something that will really make an impact on the epidemic now," he adds.

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