AIDS respite, no cure in 'cocktail' Virus hides in cells from drugs for years

November 14, 1997|By Jonathan Bor | Jonathan Bor,SUN STAFF

Three new studies, including one at the Johns Hopkins School of Medicine, have quashed the hope that some patients taking triple-drug "cocktails" for AIDS can stop taking their medications after a few years of successful treatment.

The findings have had an immediate effect -- prompting Dr. David Ho, the famous AIDS researcher in New York City, to shelve plans to take a few patients off drugs to see if the infection bounces back.

The action was to be a bold test of his theory that the drugs were capable of curing patients within a few years.

"I think the new findings clearly point out an additional obstacle that must be addressed before eradication can be achieved," said Ho, director of the Aaron Diamond AIDS Research Center.

L "That clearly is a goal for us working in the therapy area."

In the new studies, scientists performing sophisticated new tests on patients who had experienced significant improvement found that the drugs did not eradicate the disease-causing virus -- even when standard tests showed that the drugs had diminished the virus to undetectable levels.

Rather, scientists found a reservoir of virus hiding in "resting memory cells" of the immune system -- cells that lie dormant for months or even years until they are awakened to do battle against an invading microorganism.

"The bad news is that we can't get rid of this virus entirely," said Dr. Robert F. Siliciano, an associate professor of medicine who directed the Hopkins study. "The good news" is that patients who take the drugs continually -- perhaps never stopping treatment -- might survive the infection for years in reasonably good health.

In other words, patients might live a long time even if the drugs don't cure them.

Separate studies finding reservoirs of infection were reported by scientists at Hopkins and the University of California San Diego; they appear in today's issue of the journal Science.

In the Hopkins study, scientists followed 22 patients who had been treated with triple-drug therapy for up to 30 months. Nineteen patients were being treated at the hospital's AIDS clinics; three were from Ho's institute.

A third study, done by Dr. Anthony Fauci and colleagues at the National Institute of Allergy and Infectious Diseases, is to appear in a coming issue of Proceedings of the National Academy of Sciences.

Two years ago, the introduction of a new class of drugs known as protease inhibitors revolutionized the treatment of AIDS. Typically, patients take a "cocktail" consisting of a protease inhibitor and two older medications such as AZT and 3TC.

The earliest hope was that the drugs would suppress the virus and restore patients to good health without necessarily curing -- them. Doctors were amazed by the recoveries made by some patients who were able to avoid side effects and adhere to complicated dosing schedules.

But they didn't dare speak of a cure until last year, when Ho suggested that the drugs might clear some patients of all traces of virus.

According to the theory, the disease would burn itself out in a twofold process.

First, the drugs would halt the spread of the human immunodeficiency virus, which causes AIDS, by shutting down the machinery by which the virus makes billions of copies of itself. Second, cells that carry reservoirs of virus would eventually die a natural death.

Though he didn't dismiss the idea altogether, Ho didn't count on the existence of a pool of infected cells that were extremely long-lived.

These "resting memory cells" are programmed to fight particular infections, existing in a dormant state until they suddenly awaken to do battle.

Now, it appears that HIV can hide for many years in resting cells until those cells are activated. When this happens, the cells are capable of releasing huge numbers of viral particles.

Patients who stop therapy would suffer a resurgence of disease.

Yesterday, Ho said he will look for a way around this problem. One possibility is a treatment that would wake the cells from their resting state so the drugs could finish the job of wiping out the last vestiges of infection.

"We, certainly, and probably many other groups are thinking of ways that we can flush out this reservoir," Ho said.

Dr. Joel Gallant, a Hopkins physician who treats AIDS patients, said he was not disappointed by the new findings.

"We really didn't expect eradication to pan out, though we all hoped it would," Gallant said.

Pub Date: 11/14/97

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