Project seeks to predict HIV therapy response

By Bill Snyder

Vanderbilt Medical Center will lead a multi-center “pharmacogenomics” project to identify human genetic variations that may affect response to HIV therapy.

The project, which includes researchers from Harvard, Cornell, and the University of Western Ontario, will be supported beginning this month by a five-year, $4 million grant from the National Institutes of Health (NIH).

“Over the past decade Vanderbilt investigators have made seminal discoveries regarding the ability of human genetics to predict response to several HIV drugs,” said David Haas, M.D., principal investigator of the grant and director of the Vanderbilt AIDS Clinical Trials Program.

The new grant “will allow investigators to more thoroughly identify genetic polymorphisms that predict efficacy and toxicity of frequently prescribed HIV medications,” Haas said. “This information may ultimately be used to translate genetic testing into routine clinical care, and benefit HIV-infected patients worldwide.”

The project will use DNA samples together with clinical trials data from HIV-infected patients to see whether genetic variations, called polymorphisms, affect the effectiveness and toxicity of the drugs patients take to control their infection. The researchers will focus on variations in genes involved in drug metabolism and drug transport.

These studies also will assess the cost effectiveness of using genetic testing to help doctors choose which HIV drugs are most likely to work and will have the fewest side effects in their patients.

“This information may ultimately … benefit HIV-infected patients worldwide,” said Haas, associate professor of Medicine, Microbiology & Immunology.

Human DNA samples have been collected from more than 10,000 volunteers in randomized HIV treatment trials of the NIH-funded AIDS Clinical Trials Group (ACTG).

The samples, many of which will be used for this pharmacogenomics project, are stored in the ACTG's Human DNA Repository, which is housed in the Vanderbilt Center for Human Genetics Research (CHGR).

The ACTG is one of the world's largest clinical trials networks. Since 1987, the ACTG has enrolled more than 40,000 HIV-infected volunteers into clinical trials at Vanderbilt and academic health centers across the country.

This pharmacogenomics project also will utilize data and specimens from HIV-infected patients who participated in clinical trials in Haiti and South Africa.

Vanderbilt co-investigators on this project include Marylyn Ritchie, Ph.D., director of the Computational Genomics Core and assistant professor of Molecular Physiology & Biophysics and Jeffrey Smith, M.D., Ph.D., Ingram Assistant Professor of Cancer Research and, like Haas and Ritchie, an investigator in the CHGR.

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