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Mood of Realism Prevails at World AIDS Conference

TIMES MEDICAL WRITER

Two years after a similar meeting in Vancouver introduced what appeared to be a miracle class of AIDS drugs called protease inhibitors, the world’s AIDS researchers are meeting here today with a chastened sense of reality.

Although the new drugs and the advent of “cocktail” therapies employing three or more drugs in combination have dramatically reduced the AIDS death rate in the United States and Europe, physicians are starting to see troubling side effects associated with their long-term use and the appearance of new drug-resistant strains of HIV.

Physicians had also predicted that cocktail therapies would eliminate the virus from the body, but HIV has proved surprisingly resilient, clinging to protected sites in the body even after three years of treatment.

The high cost of the drugs has also precluded their use by 95% of the world’s 30 million HIV-positive people.

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Despite increased success with behavioral interventions, moreover, the number of new cases of HIV worldwide continues to grow by 16,000 per day, with more than half of those among people in the flower of their youth--under age 25. And despite President Clinton’s call last year for a 10-year project to develop a vaccine, experts say we are no closer to having one now than we were in Vancouver.

“This is the Conference of New Realism,” said Dr. Peter Piot, executive director of UNAIDS. After the “hubris of Vancouver,” he added, “we now have a more realistic appreciation of where we are in terms of treatment.”

“There is a lot of frustration and anger that many [HIV-positive people] have not benefited from the new discoveries,” said Dr. Helene Gayle of the U.S. Centers for Disease Control and Prevention.

“It was a mistake to make [so much] noise when the therapy breakthroughs came through” in Vancouver, said virologist Robert Gallo of the Institute of Human Virology in Baltimore. Researchers there were “too cocky.” They should have been saying, “This is a good advance, but there is a lot more to be done.”

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But all is not gloom and doom as 12,000 researchers gather here for the 12th World AIDS Conference.

French researchers reported that using caesarean sections during birth, coupled with the HIV-fighting drug AZT, could nearly eliminate transmission of the AIDS virus from mother to child.

And results are expected to be presented on new drug dosages that can reduce the number of pills a patient must take each day, on new drugs just coming out of the research pipeline, and on new ways to limit transmission of the virus.

Some good news has already begun to trickle out.

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Last week, the manufacturers of several AIDS drugs said they would reduce prices by as much as 75% in developing countries. The experimental program will begin in Uganda and the Ivory Coast.

Glaxo Wellcome PLC will sell a combination of AZT and 3TC for $200 per month, a 60% reduction in cost. But even that may be too high for most patients. The average annual per capita income in Uganda is about $300; in the Ivory Coast it is about $650.

Dr. Joseph Saba of UNAIDS, a United Nations agency, hopes that the governments of those countries will increase funding for AIDS treatment programs if the first distribution is successful. “We must show them that AIDS justifies investing public funds,” he said.

On the research front, new evidence suggests that mother-to-infant transmission of the AIDS virus during birth can be reduced almost to zero. Such transmission is responsible for the vast majority of the 2.7 million child deaths since the AIDS epidemic began.

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At a Saturday symposium sponsored by the American Medical Assn., Dr. Laurent Mandelbrot of the Cochin Hospital in Paris reported on a large French trial studying the use of a short course of AZT combined with caesarean sections.

Transmission of HIV from mother to child occurs primarily during the birthing process, so interventions have focused on that phase. Previous studies have shown that AZT use alone reduces the risk of transmission by about two-thirds.

That finding was supported by the research on the 2,834 mother-infant pairs in the French Perinatal Cohort. Among mothers who received no treatment at all, 17.2% transmitted HIV to their infants. Among those who received AZT and underwent a normal vaginal birth, the percentage dropped to 6.6%. But among those who took AZT and had a C-section, only 0.8% transmitted the virus.

“This is good news,” Mandelbrot said, particularly for countries including Brazil, South Africa and Thailand, where C-sections are performed routinely and safely. But in much of Africa, he noted, “it is not the way to go.” On most of that continent, the technology for carrying out the operation is not available and the complications of C-sections would take more lives than the operation would save.

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At the same symposium, Dr. Roy M. Gulick of Cornell University Medical College in New York City reported on the longest study of combination therapy conducted to date and found good news and bad news. Patients in the study have now been enrolled for two years.

The good news is that 80% of the patients who received triple therapy (a combination of AZT and 3TC with the protease inhibitor indinavir) as their first treatment had blood HIV levels below the limits of detectability two years later.

Their immune systems had also undergone substantial restoration.

Among the 20% for whom the combination therapy did not work, the main reasons were lack of compliance with the complicated therapies and withdrawal from the trials because of side effects, such as excessive nausea.

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The bad news came in patients who had already been treated with one or two drugs before they began triple therapy. Among this group, only 35% to 40% still had undetectable levels of the virus after two years. The problem, Gulick said, is that patients treated with only one drug at a time quickly develop resistance to that drug. When other drugs are added to the regimen, the combination is less effective.

“This explains why a high percentage of patients at some clinics are failing combination therapy,” he said. It is absolutely essential to use triple therapy as the first treatment for HIV-positive individuals, he added, and treatment should begin as soon as the infection has been identified.

There are several ways to learn more about the proceedings at the meeting. As many as 50 presentations daily, as well as highlights, will be available on the World Wide Web at https://webcast.aids98.org, including audio presentations and slides.

Summaries of many of the important papers prepared by physicians will be available at https://www.healthcg.com/hiv beginning Monday.

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The San Francisco AIDS Foundation will present an interactive telephone conference from Geneva at noon Thursday Pacific time. Several physicians will summarize research presented at the meeting and answer questions from callers. To register for the conference, call (800) 707-BETA before noon Thursday.


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