Researcher's Finding Lends Hope for Aids Cure

RALEIGH, N.C. -- A newly recruited University of North Carolina-Chapel Hill researcher has successfully attacked traces of dormant HIV in people, leading some to suggest that a cure for AIDS may be within reach.

For 20 years, scientists have searched for a means to extinguish the human immunodeficiency virus, which infects 13,000 new people a day worldwide. Today's best drugs -- expensive and inaccessible to many -- can only keep the virus in check. They can't destroy inactive HIV.

But with results from a "proof of concept" study, David Margolis argues that a drug developed to treat seizures and depression appears able to flush out dormant HIV, making it vulnerable to treatment.

"I'm very nervous about how the message comes out. But I think this offers hope," said Margolis, a doctor-scientist whose findings appear today in the British journal The Lancet.

The find is stirring excitement among some AIDS researchers. The drug Margolis used, valproic acid, has been in circulation for decades. Doctors know it's safe. And it's available in generic forms, so introducing it as an HIV treatment would be less costly than launching a new drug.

"This is a milestone. It opens the possibility that we can work this out. Last week, it was unworkable," said Jean-Pierre Routy, an HIV researcher at McGill University in Canada who is also evaluating valproic acid's promise.

But not everyone is convinced. Eradicating HIV is one of medical science's toughest challenges. And Margolis has not proved he has cracked it, said Robert Siliciano, a Johns Hopkins University researcher who helped identify HIV-infected "sleeper" cells that lie dormant and then bloom.

"This is a very difficult problem. I don't think that we should be talking about curing anyone yet," Siliciano said.

Finding a way to extinguish the virus would transform HIV infection from a lifelong disease controllable by drugs to one that's curable. That could dramatically cut treatment costs worldwide.

HIV remains one of the most devastating threats to human health, with more than 39 million adults and children now infected worldwide. Those who are most vulnerable to suffering and death lack access to costly drug combinations, which keep the virus from running rampant and disabling the body's immune system.

In North Carolina, more than 27,000 people are thought to be infected with HIV. Treating each can cost $35,000 a year.

Margolis, who treats patients and conducts research, was inspired to test valproic acid by recent molecular insight into HIV, including Siliciano's findings.

In his Texas laboratory, Margolis, 45, concluded that a series of molecular messages probably keeps HIV silent in certain immune system cells, which scientists can now track. This inactive state allows HIV to hide from today's drugs.

Research from a cancer laboratory later convinced Margolis that valproic acid might scramble the very message that quiets HIV in the cells. So he gave the drug to a small number of Texas patients with HIV, along with higher doses of their conventional HIV drugs, and looked for effects.

He found them. After the patients took doses twice a day for three months, three out of four patients had a 75 percent drop in cells harboring the "latent" infection.

"This finding, though not definitive, suggests that new approaches will allow the cure of HIV in the future," his Lancet article boldly states.

Margolis stresses that much work must be done to fully evaluate this treatment, which he expects could not reach patients for at least a decade if it bears out. He intends to continue testing the drug in patients, including some in North Carolina once he gets UNC approval.

If Margolis gets promising results, he envisions expanding those tests to parts of the world where HIV is spreading fastest, including Africa, where UNC faculty already conduct research.

"There's a lot of work to do," said Margolis, who started his $159,000-a-year post at UNC on Aug. 1.

For Margolis and others to be successful, they must prove that they can eliminate every little bit of HIV, some of which might hide in cells that don't respond to valproic acid, Siliciano said.

Even leaving the tiniest trace of virus could cause trouble, because the bug reproduces exponentially when it becomes active.

Myron Cohen, chief of infectious disease at UNC-Chapel Hill, predicts Margolis' findings will inspire more scientists to rejoin the race to extinguish HIV.

"Regardless of the level of difficulty, we have no choice but to go down this road," Cohen said. "All David is trying to do is get the ball rolling." Editor Notes: (From McClatchy News Service, for use by New York Times News Service clients.)