The Associated Press - Saturday, November 30, 1996 10:30:00 PM.
Daniel Q. Haney, AP Medical Editor

In those days, taking care of AIDS meant little more than easing the inevitable. It was a depressing business, emotionally numbing and awful for all involved. Death was the only certainty.

"I was fried," Rashbaum remembers. He took eight months off, cleared his head and thought seriously of cutting back his AIDS practice.

Last winter, though, everything began to change. It became apparent that a mixture of three AIDS drugs -- a new kind called a protease inhibitor, plus two older ones -- could do something that many in Rashbaum's profession had almost given up hope on: Stop the virus cold.

"Now, it's a pleasure to give people hope," said Rashbaum, who is in private practice in Washington, D.C. "I treat people who are going to live. The staff feels it. We feel it. It's a whole different ambiance."

All over the country, doctors are still in awe at what they are seeing.

When the treatment works -- and for most, it does -- people who thought they were doomed soon start to look and feel better. Kaposi's sarcoma skin cancers, a common complication of AIDS, begin to disappear. Rampant infections slow and stop.

And in the bloodstream, the once-staggering amounts of AIDS virus drop below the level of detection. The number of helper T cells, the virus's primary target, begin to rebound.

One of Rashbaum's patients was down to a disastrously low seven T cells per milliliter of blood. The fellow even gave them the obvious names: Sleepy, Dopey, Doc ... Now, they are above 200 -- too many to name -- and still climbing.

Moreover, AIDS is killing fewer people. At some hospitals, deaths from AIDS have dropped in half over the past year.

"I'm not strongly religious, but I use the word `miraculous' in some cases," said Dr. Patricia Kloser, director of AIDS services at University Hospital in Newark, N.J. "It's incredible what's happened to some of my patients."

She remembers a man who literally was on his death bed, his lungs filled with AIDS-related pneumonia, too weak even to get up to use the bathroom. Now, he has gained 50 pounds, rides his bike all over New Jersey and wants to go back to work.

Just about every doctor in AIDS has these stories.

"I've been doing this since 1983, and I never dreamed I would see things like this. It's been truly uplifting," said Dr. Harold Katner of Mercer University in Macon, Ga.

All this euphoria is mixed with caution, however. Some patients don't get better at all. Others have stopped taking the medicines because of bad side effects, such as kidney stones, diarrhea and fatigue.

Even more troubling, many doctors wonder what will happen after their patients have been on the drugs for a while. While these new combinations -- or "cocktails," as doctors like to call them -- dramatically hinder the virus' ability to reproduce, they probably don't wipe it out completely.

"One of the things we worry about is how long these effects will last," said Dr. Philip Keiser of the University of Texas Southwestern Medical Center in Dallas.

Here's the problem: Older AIDS drugs, such as AZT, temporarily slow the virus, but not enough. Eventually, HIV mutates so it is impervious to each new medicine. With protease inhibitors in the mix, viral reproduction is so low that these drug-eluding mutations don't occur -- at least at first.

But doctors wonder whether mutations eventually will destroy the power of protease inhibitors, too.

"We don't think the benefits are going to last indefinitely," said Dr. Joel Gallant of Johns Hopkins University. "They will prolong life, but most of us feel in most cases there will be a limit."

How long? Many say they expect to add years to patients lives -- perhaps even decades. And while it is theoretically possible for protease inhibitors to cure some people if taken early enough in the disease, that is unlikely to be true for most.

Already, doctors are beginning to see the cocktails lose their punch in a few patients, usually ones with advanced cases. Dr. Jerome Groopman of Beth Israel Deaconess Medical Center in Boston said 10 percent to 15 percent of patients who initially respond begin to fail again after nine months or so.

"It would be very foolish to assume this is a cure," Groopman said. "It buys precious time, and that time is variable."

Doctors say the chance of avoiding resistant viruses is best if patients get three drugs they have never had before. But many with long infections already have taken virtually everything on the shelf except protease inhibitors. Adding them alone almost guarantees resistant HIV.

Another problem is the complicated mix of drugs involved. Some patients must swallow two dozen pills, each at just the right moment, every day. Even missing a few doses increases the risk of resistant viruses. And once someone's virus outsmarts protease inhibitors, there is no second chance.

"I don't give a patient a protease inhibitor until I have a good long talk with them, and they understand this is their only shot," Gallant said.

Patients with resistant HIV can pass it on, spreading an infection that is impossible to treat. Therefore, many doctors -- but not all -- are wary of prescribing protease inhibitors when they are likely to fail, such as for patients who already have used all the available drugs or drug addicts who cannot stick to their medication schedules.

The current drugs are hardly the last word in AIDS therapy. The Pharmaceutical Research and Manufacturers of America says 122 new AIDS medicines and vaccines are in development, and doctors hope some of these will be ready when their patients run out of time on protease inhibitors.

"We used to try to keep patients alive until the next Christmas," said Dr. Michael Saag of the University of Alabama in Birmingham. "Now, our goal is to keep them alive for the next decade or two or three."

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