Master of microevolution  pg. 5

Another problem is that cellular proteins called transporters can prevent the drugs from even getting to the virus in the first place. Transporters are designed to keep cells clean, by pumping out toxic materials—but they also can eject anti-retroviral drugs.

Genetic differences in individuals also seem to play a role in the effectiveness of drug therapy, and the severity of side effects.

David Haas, M.D., principal investigator of the Vanderbilt AIDS Clinical Trials Center, and his colleagues have found that African-Americans are six times more likely than Caucasians to have a polymorphism, or genetic variation, that limits the ability of a cellular enzyme to break down a common AIDS drug. The result: higher levels of the drug and a greater frequency of neurocognitive side effects, including mental confusion.

All this makes therapy extremely complicated. Doctors must isolate the virus from their patients, determine its genetic sequence in the laboratory, and pick the drugs that are most likely to inhibit that particular strain of HIV. “It’s individualized therapy,” says D’Aquila, who helped pioneer HIV sequencing technology and resistance testing. “It’s in constant flux. Every couple of months there’s some new earth-shaking development.”

The good news is that there are a lot of tantalizing leads to follow: natural factors and other compounds that can block HIV inside the cell; advanced technologies that enable scientists to “see” what’s going on at the cellular and molecular levels; and new ways of boosting immune responses.

“I have great optimism that with some of the brightest minds of our generation focused on this problem, that we will have an effective AIDS vaccine,” Haas says. “I envision one day in the distant future when we have a single pill that treats HIV in almost all people. But … the only way we’re going to get to that is with continued, vigorous support of research.”

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