AIDS virus may stay a lifetime

Drug therapy hailed even as virus proves able to hide in cells

April 27, 1999|By Jonathan Bor | Jonathan Bor,SUN STAFF

Researchers have found evidence that the AIDS virus can hide in the immune system for 60 years or more, evading eradication.

The finding, by scientists at the Johns Hopkins School of Medicine, quashes the hope that patients taking today's best medications will be able to stop taking their drugs once the virus burns itself out.

For now, there are no signs that the virus ever goes away.

"The virus has a mechanism that allows for lifetime persistence," said Dr. Robert Siliciano, a Hopkins AIDS researcher. "It is not going to go away without a specific intervention which we don't have yet."

At the same time, Siliciano emphasized that most people who faithfully take their drugs are doing remarkably well even though they cannot rid themselves of small reservoirs of infection.

"Clinically, they are doing great," he said.

The study, published in this week's Nature Medicine, builds upon discoveries by Siliciano that were pivotal to understanding how the virus persists despite drug therapy.

The AIDS virus is unusual in that it infects cells in the immune system, crippling the body's ability to fight infection.

One category of cells it infects are "memory cells" -- white blood cells that are programmed to fight off a particular bug, such as the measles or influenza virus. The cells lie dormant for years, waiting to recognize the invader and mount a counterattack.

AIDS drugs are effective only upon cells that are active; they work by shutting down the process by which the virus hijacks a cell's machinery to make copies of itself.

By hiding among dormant cells, the virus has a way to evade even the best medications.

In the study, scientists periodically drew blood samples from 34 patients for two years. The patients were taking drug combinations that include protease inhibitors, a class of medications that have revolutionized AIDS therapy.

Using a sophisticated test that was invented in Siliciano's lab, scientists tracked the number of memory cells that were silently infected -- and found they remained about the same.

Then, using a mathematical model, they estimated that the latent infection would remain for about 60 years. In effect, doctors can assume that patients will remain infected for the rest of their lives even if they are taking their medications and feeling healthy.

Survival of memory cells

Though scientists do not have a complete picture of how memory cells work, Siliciano said it is not surprising that they remain dormant for so long.

"The immune system is designed to maintain long-term memory for previously encountered infections," he said.

"Part of that capacity to remember is due to the survival of memory cells. If you have measles as a child, you're protected 60 years later."

Two years ago, as Siliciano's work developed, scientists were forced to abandon the hope that patients whose viral levels could not be measured by standard tests could stop taking their drugs after about three years.

They had predicted, erroneously, that the disease could be cured in a two-stage process: Medications would keep active cells from budding new virus; dormant cells would burn out, dying a natural death.

Now, confronted with the possibility that some infected cells could last forever, scientists are quick to say the future for AIDS patients is far from bleak.

"I want to caution people not to think it's such horrible news and that these drugs don't do any good," said Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases. "They are still extremely important in improving the quality and the duration of life."

Fauci is among the scientists who are looking for new ways to eradicate the virus. One possibility is to boost the immune system so that it could wipe out whatever virus emerges after a patient goes off medication, he said.

Long-term drug problems

Without new therapies, he acknowledged, it will be difficult to keep many patients on medications for untold years.

Some experience side effects that make it difficult to continue. Others can't cope with the task of taking many drugs on different schedules. When they slip, the virus often becomes resistant to therapy.

"Though the medications are getting easier, people have complicated lives and to try to impose that sort of order on people is pretty hard," said Dr. Joel Gallant, who directs Hopkins' AIDS outpatient clinic.

Dr. John Bartlett, chief of infectious disease at Hopkins, said he remains optimistic that AIDS can become a manageable disease similar to diabetes or hypertension. The rapid pace of drug development offers the hope of new therapies that will be simpler and less toxic, he said.

"If we continue to make these kinds of strides, we may have the opportunity for people not to take medications for the rest of their lives," he said.

"If they do have to take medications, they may be much easier."

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