A NEW ATTACK ON AIDS

By Christine Gorman

Dan Cusick, 37, of San Francisco learned last July that an AIDS-related illness was eating away at his brain and would probably kill him by October. In a last-ditch effort to save his life, his doctors gave him three anti-HIV drugs all at once. Within weeks, the lesions inside his head started to disappear. And tests could no longer find even a trace of the virus.

John Rife, 54, of Waimanalo, Hawaii, was getting clobbered by everything from virulent pneumonia to malignant lymphoma. His doctors started him on three anti-HIV drugs. Within a month, his devastated immune system showed signs of recovering, the cancer had vanished and the level of HIV in his blood was so low it was undetectable.

Linda Grinberg, 45, of Brentwood, California, was battling fungal infections, cytomegalovirus and exhaustion when doctors put her on a multidrug regimen against her HIV infection. "It's given me back my life," she says. "A year ago, it was difficult even to get dressed. I really felt I was at the end of the line."

Everywhere they turn these days, doctors and patients are hearing good news about AIDS. In the past seven months, the U.S. Food and Drug Administration has approved five new medications that interfere with HIV's ability to reproduce. Hundreds of desperately ill patients are regaining their health. As scientists prepare to attend the 11th International AIDS Conference in Vancouver, Canada, next week, an unprecedented sense of hope has started to spread among physicians and patients alike. Doctors are even daring to whisper among themselves that a cure could be at hand.

At the center of this optimism is a bold new approach to AIDS treatment called combination, or cocktail, therapy. It's a simple idea: HIV mutates so fast it eventually becomes resistant to any drug that doctors throw at it. Two drugs, attacking the virus in two different biochemical ways, can keep HIV off balance and make its evasive tactics harder--though not impossible--to sustain. But even a slippery virus like HIV can't deal with a three- or four-pronged assault. So said computer models, at least. But until late last year, no one had come up with a third drug that could test the theory.

Then the FDA approved a new medication called saquinavir. One of the so-called protease inhibitors, it attacks the virus at a previously untargeted step in its reproductive process. Several similar drugs have since followed. The agency also approved a medication called 3TC. Although it works much like AZT, the two act as a chemical tag team: after HIV becomes resistant to AZT, it is still vulnerable to attack by 3TC. If it then develops resistance to 3TC, it suddenly loses the ability to fend off AZT. Multiple-drug therapy had finally become possible.

Doctors first tried the treatment on their sickest patients. Not everyone responded or could even tolerate the combination of powerful drugs. But in a number of cases, the cocktail forced the disease into remission. Doctors watched in amazement as their patients' blood tests showed a precipitous drop in the amount of HIV. "We have seen patients whose viral load has gone below our ability to find it," says Dr. Paul Volberding of San Francisco General Hospital. "The question is, Can we keep it that low, and what will happen to the body with that kind of treatment?" There's the real possibility that the therapy will prove too toxic to continue for very long. Or that HIV may find hiding places in the body from which it can eventually launch devastating counterattacks.

But if combination therapy can help people with longstanding HIV infections, it could do even more for those who have just contracted the virus. That's exactly what Dr. David Ho of the Aaron Diamond AIDS Research Center in New York City and his team of virologists are trying to confirm. Ho believes that if you hit HIV early enough and hard enough, you ought to be able to eliminate it completely from the body. He and his co-workers are already testing this idea, and will present the results from their first experiments at next week's conference.

Finding people with brand-new HIV infections isn't easy; most don't get tested that quickly. But last July the researchers managed to find 12 men who had been infected with HIV for no more than 90 days. The men have been on combination therapy ever since, and Ho can't find a trace of the virus in their blood. In the next few weeks, he plans to take biopsies of their lymph nodes to see if the virus is hiding there, out of reach of both the drugs and the blood tests. If the nodes are clear, Ho plans to take some of the patients off their medication and see whether HIV bounces back. And if the biopsies do turn up infectious particles, Ho will have to choose another ingredient to add to his cocktail. Either way, Ho says, "the whole field has progressed in such a way that people are beginning to address the question--which was unheard of before--of eradicating the virus."

Combination therapy still has its problems. The medications can interact with one another to cause side effects. Even by themselves they can cause severe diarrhea, abdominal cramps or anemia. Some of the drugs have to be taken on an empty stomach, others on a full stomach, so it can be hard to stick to a regimen. Yet if patients skip even a single dose of any one drug, the HIV could press this small advantage to mutate into a strain that resists all current medicines. Nor is everyone so sure that a cure is in sight. "Virologists have started using that word," says Dr. Donald Abrams of the University of California, San Francisco. "You're not going to hear me use it. I think it's irresponsible."

But no one denies that tremendous strides are being made. The current research is prompting the International AIDS Society to announce new treatment guidelines next week. Scientists are starting to isolate naturally occurring compounds called chemokines that appear to protect some people who are infected with HIV from the effects of the virus. These substances could form the basis for a future, even more powerful cocktail. For the first time in a long while, it doesn't seem naive to dream that there will one day be an end to AIDS.

--Reported by Laird Harrison/Oakland and Alice Park/New York

With reporting by LAIRD HARRISON/OAKLAND AND ALICE PARK/NEW YORK