United Press International - Monday, April 26, 1999

In another related report, scientists also found that these AIDS drugs, known as highly active anti-retroviral therapy (HAART), may weaken the body's own ability to fight the AIDS virus. HAART consists of drugs like AZT, combined with newer drugs known as protease inhibitors or non-nucleoside reverse transcriptase inhibitors.

Taken together, the two studies suggest that patients can keep the Human Immunodeficiency Virus (HIV) at bay, but only if they stay on difficult and expensive drug regimens, which scientists say is not practical because of costs, side effects and the potential for the development of resistance.

They also say that curing AIDS, a hope kindled in researchers after promising initial results with drug cocktails, will require new medications or other strategies, such as anti-HIV vaccines.

Both studies are published in the May issue of the journal Nature Medicine.

In one study, scientists from Baltimore's Johns Hopkins University School of Medicine monitored the immune systems of 34 HIV infected patients for two years. All the patients were taking HAART, and were in good health.

Scientists had known that HIV tucks itself into resting T-cells, rare cells that provide long term protection against diseases like measles after exposure to the infectious agent.

In the new research, they found that infected resting T-cells, also called memory cells, can survive for more than 60 years, giving the AIDS virus a safe place to hide for a lifetime.

Immunologist Robert Siliciano says, "The results are pretty shocking. The survival of these cells is remarkable."

When the three-drug cocktails first showed the potential to reduce the amount of HIV to undetectable levels about three years ago, doctors became excited that they had found a way to wipe out the infection, he says.

But, they soon discovered that undetectable does not mean that the virus is gone. Earlier work by Siliciano and other leading research groups found these hidden reservoirs. The virus may not have been attacking its main target, immune system cells known as CD4, and they weren't causing disease. Nevertheless, they are still in the patient's system.

Siliciano says, "This is quite depressing news, obviously."

He says, "This means you probably can't stop and expect the virus will be gone. You can't take medicines and wait out the virus."

Stopping therapy would allow the infection to rebound, which is what happens when patients stop taking drugs in a matter of weeks.

Siliciano, lead author of the paper, says, "It was previously shown that the virus could persist. What was unknown is how long these cells last."

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, says, "It's a good paper, an important paper. But it tells us we really have our work cut out for us."

Fauci says it is not feasible to keep patients on these difficult drug regimens for a lifetime. Most patients taking the drugs have been on them for two or three years, with the longest experience of about five years in patients who participated in the clinical trials testing the drug cocktails.

To cure AIDS, he says, scientists will have to figure out ways to actively flush out that latent pool of virus, or find ways to get the immune system itself to keep the virus in check.

He says, "We have to figure out creative ways to deal with it."

In the second study, led by Louis J. Picker of the University of Texas Southwestern Medical Center in Dallas, scientists found that even AIDS-ravaged immune systems try to fight back, producing cells that are primed to attack the virus.

This response is one of the reasons why some HIV-infected people become long-term non-progressors. Their immune systems are strong enough to successfully ward off the disease.

But, the scientists say, the number of these anti-HIV cells diminish over the course of long-term drug therapy.

To measure this, Picker and his team created a method to screen immune cells to see if they were HIV-specific, trained to attack the virus. As expected, uninfected people had none of these cells, while long-term non-progressors were loaded with them.

They also found AIDS fighting T-cells, however, in patients whose disease was progressing, says Picker.

In the second part of the study, Picker says his team looked for HIV- specific T-cells in patients who had been undergoing HAART therapy. They found that the number of cells dropped or had a significantly weakened response to the virus after drug treatment.

This finding suggests that long-term strategies to fight AIDS will have to include programs in which patients periodically stop taking drugs, a sort of vacations from the therapies, or the addition of vaccines into treatment programs.

The Centers for Disease Control and Prevention in Atlanta estimates that about 900,000 Americans are infected with the AIDS virus.
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