Researchers Gather for Largest AIDS Meeting : Health: Discussion of incremental gains will be held against a backdrop of protest. Activists are impatient at the rate of progress in finding effective treatments.

The world’s largest annual gathering of AIDS researchers opens today in a city raw with grief over the AIDS deaths of 5,600 of its residents and at the same time hopeful for a medical breakthrough to save thousands of other San Franciscans and millions worldwide.

For the next five days, the Sixth International Conference on AIDS is expected to attract 12,000 scientists, policy makers, drug company officials and AIDS workers, despite a boycott by more than 100 organizations to protest U.S. travel restrictions on foreigners infected with the human immunodeficiency virus, which causes AIDS.

Along with the delegates will come 2,000 journalists and an unknown number of activists, including about 150 members of ACT UP/Los Angeles. Between 100,000 and 250,000 gay men and lesbians will gather Sunday, the conference’s closing day, for San Francisco’s annual Gay Pride Parade. An estimated 30,000 of this city’s 727,000 residents are infected with HIV.

While scientists are expected to report some intriguing but incremental gains in their quest for effective treatments and a vaccine, AIDS activists impatient for speedier progress have scheduled large demonstrations and acts of civil disobedience, and violence is feared.

On Tuesday evening, eight demonstrators were arrested peacefully after crossing police lines while protesting the travel restrictions at the regional office of the U.S. Immigration and Naturalization Service. Later, an estimated 350 protesters then marched from the INS office up Market Street and, without warning, entered the Marriott Hotel, a conference site. As bewildered tourists looked on, the protesters streamed into the atrium area chanting, “Ten years. A billion dollars. One drug. Big deal!”

Most of the protesters then left the hotel, but about two dozen sat in the lobby, blocking the hotel’s main entrance, and began chanting, demanding 2,000 tickets to the conference.

The demonstrators left the hotel voluntarily at about 9:30 p.m. after conference organizers agreed to meet with their representatives to negotiate the demand for admission to the conference. The demonstrators’ mood reflects the uncertain state of research on the cause and possible treatments of this mysterious disease: By what precise mechanism does HIV kill? Does HIV act alone? Or, as HIV discoverer Dr. Luc Montagnier of the Pasteur Institute now suspects, does the virus need accomplices known as mycoplasmas in order to do its dirty work?

And--most vitally for a world that is facing the prospect of a cumulative total of 6 million people with fully developed AIDS by the end of this decade--can the virus be stopped? Can the immune system, once damaged, be repaired? If so, how and when?

Conference organizers, based on their examination of some 2,500 research abstracts accepted for presentation, say that many new insights are likely to emerge as researchers trade hundreds of tantalizing leads.

Together, these gains in knowledge about the virus, where it came from and how it interacts with its human host, will serve as clues that they are confident will lead to the eventual development of HIV treatments that are more effective than AZT--now regarded as a stopgap, at best--and a vaccine. But few leading scientists expect the battle to be won before the middle of the decade, at the soonest.

“We are getting to know the enemy,” said University of California, San Francisco, virologist Dr. Jay Levy, chairman of the conference’s Basic Science track. “The old thinking was: Once you find the virus the next step will be easy. But this virus is proving to be a formidable adversary. It is fighting for its survival, just as we are.”

The goal of making HIV infection a “chronic, manageable condition”--the buzzword of last year’s conference in Montreal, discussed by many as if it were around the corner--won’t be achieved until the mid-1990s, predicted Dr. Anthony S. Fauci, chief of AIDS research at the National Institutes of Health. A vaccine should be widely available by the year 2000, he added.

Fauci’s predictions, based on his vantage point at the top of the nation’s AIDS research pyramid, reflect the stuttering progress of AIDS research. In the past year, for example, good news about the ability of AZT and other drugs to stave off fully developed AIDS has been offset by an substantial increase in cancers and other lymphomas among people living longer with HIV infections.

Other bad news on the treatment front in the past year included the failure of the highly touted drug CD4, on which many top scientists’ had pinned their hopes, and new data underscoring the seriousness of AZT resistance.

On the other hand, there have been significant advances in treatments for some of the opportunistic infections that plague AIDS patients. Another hopeful sign: Anecdotal reports that the much-touted drug Compound Q has led to dramatic improvements in about 10% of the patients tested in an underground trial conducted by Project Inform, a clearinghouse for treatment information.

There is also evidence that by rotating AZT with such other antiviral agents as DDI and DDC, which are still being tested but have been made available on a compassionate-use basis to the sickest AIDS patients, viral resistance can be minimized.

Despite progress that has added months or even years to the lives of HIV patients receiving state-of-the-art treatment, the clinical picture remains grim.

AIDS weakens, then destroys the immune system, leading to a cascade of illnesses affecting practically every major organ system. Patients are often rendered blind, disfigured, demented and wracked with pain, pneumonia, tuberculosis, diarrhea, infections and cancer.

Scientists are more convinced than ever that, despite the currently imperfect treatment options, it is urgent for people who believe they may be infected to find out and seek treatment early.

“The further the immune system deteriorates, the more infinitely difficult it becomes to reconstitute,” said Fauci. He advised infected people to “get as much mileage as they can out of AZT.”

“As a scientist, I know that we have made, and continue to make, significant progress,” added Dr. Norman Letvan of the New England Primate Research Center. “But I don’t know whether I would feel the same way if I were infected with HIV and felt the clock ticking,” he added.

Researchers say some of the most exciting recent discoveries are in research on vaccines to protect the uninfected.

“After years of sitting through meetings and hearing, ‘This approach didn’t work, that approach didn’t work,’ we finally have some basis for real optimism,” said Dr. Dani Bolognesi, professor of medicine at Duke University Medical Center.

In the last year, chimpanzees, macaque monkeys and mice containing human immune-system cells have been protected against infection with HIV or similar viruses through immunization with various vaccine preparations.

With the possibility of producing a vaccine becoming more realistic, it is now a matter of doing “systematic, step-by-step, grunt science,” said Dr. Murray Gardner of UC Davis.

A vaccine could even help people who are infected but haven’t yet gotten fully developed AIDS, Bolognesi said. A vaccine that immunizes the uninfected “might also be able to tip the balance against the virus in people who are already infected” by stimulating production of virus-neutralizing antibodies, he said.

Still, Fauci believes that a combination regimen of several antiviral drugs and immune-system boosters will be needed to keep HIV at bay and patients healthy.

Strategists hope to tackle the problem of AZT resistance by rotating the drug with other drugs. Furthest along in clinical trials are DDI and DDC, though other drugs under investigation in this category, which are known as nucleoside analogues, include D4T, AZDU, FDDC, A-69992 and FLDDA.

Other classes of drugs are being developed to attack the virus at many of the 15 different steps scientists have identified in its life cycle.

The first step, during which free-floating HIV in the blood stream latches onto T4 Helper cells--white blood cells that are key sentinels of the immune system--has been the focus of much investigation.

Through genetic engineering, scientists manufactured a substance known as CD4, a copy of the cellular receptor through which HIV gains entry into T4 cells. The idea: to flood the body with CD4, which would then serve as a decoy to “coat” or “soak up” the virus, sparing the crucial T4 cells.

It was an elegant theory, but the drug didn’t work. “Everybody was so excited, the mentality was: ‘Let’s make a lot of it and shoot it up into patients,’ ” said Dr. David Ho, a professor at UCLA who moves next month to New York University to head the new Aaron Diamond AIDS Research Center.

But what worked in test-tube experiments failed to work in humans because, Ho said, scientists neglected to test the drug against virus strains drawn from AIDS patients. Instead, the drug was tested against laboratory strains of the virus, which differ considerably from viruses found in humans.

“We have learned an important lesson,” Ho said. “In science and medicine, it is best to do things the right way. Any time you take shortcuts, you usually get burned.”

Scientists are now testing so-called “second generation” CD4, which pairs the molecule with a toxin in hopes of killing off infected cells. Other drugs in development seek to inhibit essential viral enzymes, suppress multiplication signals or interfere with virus protein processing or assembly.

At least four big pharmaceutical companies--SmithKline, Hoffman LaRoche, Abbott, and Upjohn--are racing to develop a class of compounds known as protease inhibitors. Hoffman LaRoche is working on a drug that inhibits the virus’ TAT gene, thought to control viral replication.

Research aimed at developing immune-system enhancers is far less advanced than antiviral research. Even if a combination of drugs can be found to stop HIV, many scientists believe other compounds will be needed to restore infected individuals’ immune systems to normal or near normal. “Our experience has been that the immune system does not regenerate itself to normal,” even if HIV activity is shut down, said Fauci.

But researchers are finding some clues. Studying the monkey viruses known as SIV, or simian immunodeficiency virus, and a less virulent form of HIV known as HIV-2, Dr. Max Essex, a Harvard virologist, and his colleagues have identified a sequence of amino acids in the virus that appears to keep it in check. This sequence also is present in some, but not all, strains of HIV-1.

When Essex studied U.S. patients infected with HIV-1, those whose viral structure included this particular amino-acid sequence “clearly lived longest.”

“It seems effective in conferring immunity,” said Essex, a finding confirmed by other researchers looking into why some pregnant women transmit HIV to their babies and others do not.

These findings--that different strains of the virus have different levels of infectiousness--provide key knowledge for the development of therapeutic agents and vaccines.

In addition to the search for the virus’ origins, another persistent mystery is the precise mechanism by which HIV causes disease.

Scientists such as Dr. Jay Levy at UC San Francisco find it fascinating that man and virus can coexist for years before outward symptoms of illness appear. “What tips the balance?” Levy asks. “We know that there’s a nibbling away at T4 cells. When that reaches a certain threshold, everything collapses. Why?”

Levy, in studying over 100 patients, has observed that the balance is tipped when HIV evolves into a more virulent form.

The Pasteur Institute’s Dr. Montagnier, who discovered HIV, has a different theory--one that is likely to get much attention at the conference. Montagnier believes he has identified a possible co-factor that works synergistically with HIV to kill cells.

The suspected co-factor is a mycoplasma, a primitive microorganism that lacks a cell wall. Montagnier’s finding could lead to significant advances in treating AIDS if, as he hopes, antibiotics can be brought to bear against the mycoplasma.

But other scientists remain skeptical, noting that mycoplasmas often appear in cell cultures as contaminants. The questions will keep scientists busy for years.

“Every answer brings up five new questions,” Fauci said. “The field is moving so quickly that it is a constant challenge to keep up, let alone be a leader.”

This sometimes agonizing rate of progress is what frustrates many activists. Anguished at the rising death toll, New York activist and playwright Larry Kramer recently issued a widely publicized call for a “riot” at the conference.

Though few have echoed Kramer’s call--ACT UP, which is planning demonstrations and civil disobedience throughout the conference, has a strict policy of nonviolence--a local artists’ collective is plastering the city with 1,000 copies of a poster picturing an arm wielding a flaming Molotov cocktail.

“This is a field that is infinite in what can be done,” said Fauci, adding that unfortunately “our resources, our time, our money are finite.”

“You can’t use the word ‘enough’ in science,” he said. “Enough is when the problem is solved.”

CONFERENCE NO-SHOW--Writer Larry Kramer, a leader in protesting the AIDS conference, will sit out the convention in favor of brooding in his Greenwich Village home. E1