San Francisco Chronicle; Saturday, July 4, 1998
David Perlman, Chronicle Science Editor

If one thing distinguished this conference from all the earlier ones, it was the presence among the 12,700 official delegates from 177 countries of thousands of people already infected with HIV -- many of whom played an equally active role in the proceedings -- as well as more than 3,000 doctors, scientists and community health workers from the Third World.

When the first international AIDS conference opened in Atlanta in 1985, most of the participants were American, British or French. But in those early days, AIDS was seen primarily as a disease of white gay males; it was scarcely known in Africa or Asia; the AIDS virus, HIV, had only just been isolated; and there was no panoply of drugs to treat it.

In Geneva this week, the picture was far different. Scientists could describe in greater detail than ever the structure of the virus and the tricky way it infects some cells actively while hiding silently in others. International giants of the pharmaceutical industry displayed a dozen heavily marketed anti-viral drugs -- including the four powerful new ones called protease inhibitors -- while hopeful test results were announced for at least four new ones, including another protease inhibitor in the pipeline.

One new vaccine, based on the external proteins of the virus, is undergoing clinical trials in America, and officials from Thailand agreed it will soon start undergoing trials there -- although no scientist believes it is likely to prove the final answer. A different vaccine, made from a weakened strain of HIV and developed by the Harvard University Primate Research Center, may undergo its first safety trials soon.

Dr. Bernard Hirschel, the Geneva AIDS specialist who chaired the conference in Geneva this week, described the major advances he saw emerging in the more than 5,000 presentations given in lectures or poster form during the five crowded days of the conference.

In drug therapy, he said, prospects are now real that the complex anti-viral combinations that in some cases require patients to take 25 or more pills a day on demanding schedules -- sometimes before meals, sometimes after, sometimes with water and sometimes without -- may soon be replaced by dosages of only a few pills only once or twice a day.

The difficulties of complying with such complex dosage schedules can lead thousands of patients to skip pills or abandon them entirely with disastrous -- often fatal -- results.

One of the new drugs, abacavir, made by Glaxo Wellcome, has been tested in combination with AZT and 3TC, two long-used standard AIDS drugs, and it requires only two pills taken twice a day. It has shown impressive results with few side effects after four months of treatment. Another, called efavirens and made by Dupont Pharma, holds equal promise, its makers say.

The new drug combinations also do not require being combined with a protease inhibitor, with all its problems of severe toxicity and side effects that create deforming deposits of fatty tissue. Herschel sees them as hopeful advances -- for patients who can afford them, but certainly not for the tens of millions of people with AIDS in the Third World.

Another major advance, Herschel noted, is the discovery that after long-term and highly aggressive therapy with new drug combinations, many patients whose levels of HIV have dropped to undetectable levels are showing signs that their immune systems have become active again. Such immune reconstitution, in fact, might be so powerful that Dr. David Ho, a bold researcher at the Aaron Diamond Research Institute in New York even suggested some volunteer patients might be willing to try stopping all anti-viral therapy under extremely careful monitoring to see if their immune systems might now be able to fight off the AIDS virus on their own, without any medicines at all.

On the conference's basic science front, Dr. Jay Levy, of the University of California at San Francisco, reviewed evidence indicating that while years of research focusing on efforts to attack free- floating levels of the AIDS virus in the blood of infected people has been successful, it is time now to turn to immunology.

"Like the challenges of cancer, with its transformed malignant cells," he said, "the target of AIDS research and therapy should now be infected cells."

Scientists have reported finding proteins in some immune system cells that contain as-yet unknown factors capable of blocking the ability of the AIDS virus to reproduce inside infected cells, and are also capable of flushing out and destroying latent viruses that hide for years inside certain tissues.

"Bridging virology and immunology in a creative fashion should bring us closer and faster to development of long-lasting therapies and a vaccine," Levy said.

But looking more broadly at the hectic five days of the conference, Lindner commented: "Perhaps our greatest success here "was to engage the AIDS community -- both AIDS workers as well as people with the disease and their organizations -- into every aspect of the program, on an equal footing with the rest of us, and to engage people from the South with those of us from the North. We did indeed succeed in bridging the gap -- the gap between North and South and between science and the people on whose behalf science and medicine must work."

Said Winston Zulu, a young man with AIDS from Zambia: "I have looked on this conference with joy and conflict, with rage and hope. But I think I have more hope now than I had before I came."

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