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As life goals go, David M. Margolis' is modest enough: He just wants to cure AIDS. The University of North Carolina professor has been plotting the demise of the world's deadliest infectious disease for more than a decade. Now he's planning a fresh assault with an unlikely weapon: a rarely used Merck (MRK) cancer drug.
Margolis and his team plan to test the drug, Zolinza, in about 20 patients next year to see if it can flush out the stubborn reservoirs of HIV that existing treatments don't clear. Margolis doesn't expect Zolinza to cure AIDS, yet some success would confirm he's on the right track. "It's really all about trying to move the field ahead," says the New Haven native. "You don't know until you try."
Margolis, who followed his father into medicine, is at the forefront of a renewed quest to cure AIDS, spurred by the success of drugs that control the virus and the failure to find a vaccine to halt its spread.
Governments, companies, and foundations are sinking more money into research for a cure. Merck, Gilead Sciences (GILD), and Johnson & Johnson (JNJ) are looking for drugs to purge latent HIV, and in July the U.S. National Institutes of Health offered $8.5 million for research projects aimed at finding a cure. "It's gone from being a hopeless problem to one that people think we should devote a big effort to," says Robert F. Siliciano, a Johns Hopkins University professor who first identified the cells in which HIV hides out.
Drug cocktails are capable of reducing HIV to undetectable levels without eradicating it. The virus survives with the help of an enzyme called HDAC that effectively (and unhelpfully for the patient) lulls HIV to sleep in cells by interfering with its ability to replicate. When patients stop taking their pills, the latent virus roars back to life. In a laboratory test, Margolis found that Zolinza, which appears to work by blocking HDAC, could coax HIV out of hiding in cells taken from infected patients. Now he wants to see if he can achieve the same result inside the body: "We expect to show whether it can work the way we think it does in people."
The trial will be Margolis' second bid to root out latent HIV with an approved drug. His earlier study using Abbott Laboratories' (ABT) bipolar disorder drug Depakote yielded promising results, which Margolis and others disproved. "He's an important thought leader in this field," says Romas Geleziunas, Gilead's head of biology.
Some scientists doubt a cure will ever be achieved because of HIV's ability to integrate itself into a person's DNA. "We've never eradicated an integrated virus," says David Cooper, director of Australia's National Centre in HIV Epidemiology and Clinical Research. Margolis, who apart from his research also cares for some 100 patients, is more optimistic. "I'm 51," he says. "I wouldn't be doing this if I didn't think I had time to succeed."
Studied at Harvard and Tufts University School of Medicine
Ferreting out latent HIV using drugs already on the market
Seeking a cure for AIDS