January 24, 2013

Genetic testing just one weapon in HIV/AIDS fight

Genetic testing has revolutionized the treatment of patients with HIV/AIDS. But it is not a panacea.

Genetic testing has revolutionized the treatment of patients with HIV/AIDS. But it is not a panacea.

Ultimately, it will be just one of many tools physicians will use to help their patients achieve longer, healthier lives.

David Haas, M.D.

That’s the view of David Haas, M.D., professor of Medicine at Vanderbilt University, who is internationally known for the dozens of HIV clinical trials he has led since 1994.

“We don’t try to use genetic information as a decisive piece of information to make a treatment decision, but … as one more piece of information to further improve care,” said Haas, leader of the Vanderbilt Therapeutics Clinical Research Site, part of the international AIDS Clinical Trials Group.

HIV therapy was one of the first medical fields to demonstrate the value of genetic testing.

In 2002, researchers discovered a genetic mutation was responsible for a serious hypersensitivity syndrome — fever, fatigue, gastrointestinal symptoms and skin rash — experienced by some patients who took the HIV drug abacavir. Today, routine genetic testing has virtually eliminated these reactions.

For other HIV drugs, the benefits of genetic testing are not so clear-cut.

Haas and his colleagues have made several important discoveries about how genetic variations affect the body’s ability to metabolize — or break down — efavirenz, one of the most widely prescribed HIV drugs.

In a recent study, they found most patients have genetic variations that limit the ability of the liver to metabolize efavirenz. Given a standard dose, they will have higher blood levels of the drug and a greater risk for side effects compared to other patients.

“The majority of patients would likely do as well with a much lower dose … and possibly with better tolerability,” Haas said. But reducing the dose is easier said than done.

That’s because efavirenz is always co-formulated with other HIV medications in a fixed-dose tablet. Reducing the dose of efavirenz might mean that patients would have to take — and pay for — more pills. That might be especially difficult for patients in resource-limited countries.

In addition, studies need to be done to confirm that a lower dose would be just as effective, he added.

For most genetic tests, “we’re operating in more a gray zone where … some of the decisions we would make may also have consequences,” said Haas, whose research is supported by the National Institutes of Health (grant number 5R01AI077505). “We need to always look at the big picture.”