Federal Panel Favors Early Use of AIDS Drug
A federal advisory panel on Tuesday recommended expanding the approved uses of the antiviral drug AZT to include AIDS patients in the early stages of the disease as well as those who are infected with the AIDS virus but have not yet developed outward symptoms.
In the case of the latter group, the panel said, the drug should be administered only to infected patients whose level of critical T4 cells has dropped below 500 per cubic millimeter of blood, providing evidence of damage to their immune systems.
The normal range for T4 cells, the primary targets of the human immunodeficiency virus, or HIV, is 800 to 1,200 per cubic millimeter.
The unanimous recommendations of the Food and Drug Administration’s antiviral drugs advisory committee are not binding on the agency, but it traditionally wields considerable influence in FDA decision-making. The agency is expected to go along with the suggestions.
AZT, also known as zidovudene, currently is approved only for patients with fully developed AIDS or advanced AIDS-related complex.
“Unless we intervene early . . . we are not going to accomplish the true therapeutic goals for this disease,” said Dr. Richard J. Whitley, a consultant to the panel and chairman of the independent scientific board monitoring the AZT studies.
“If we hold out a decision . . . we potentially could be doing a disservice to individuals” who could benefit from the early administration of AZT, he said.
The panel raised some concerns about the potential for HIV to develop a resistance to the drug, a phenomenon already seen in patients with fully developed AIDS. In addition, recently released results of animal studies have shown that AZT can cause cancer.
Despite these reservations, the panel agreed that the potential benefits of taking the drug at an earlier stage appear to far outweigh the risks. But they called for additional research to evaluate the long-term effects of the drug, which are unknown.
“It looks as if the effectiveness of AZT in the earlier stages of disease has been demonstrated,” said Dr. Alvin Novick, a professor of biology at Yale University and a member of the panel. “It is important to recognize this officially to inform physicians and patients across the country.”
Regarding the concerns about developing a resistant virus, Novick said he thought it “unthinkable to withhold therapy from today’s patients out of fear that we will be reducing the effectiveness of therapy 10 years from now.
“Not that I’m not respectful of patients 10 years from now--they’re just as precious--but I believe we’ll have alternative therapies for them that we don’t have for the current patients of today,” he said.
The committee action was unusual because it was taken before studies on affected patients have been published in a medical journal. However, the results of the studies of AZT on two patient groups were so compelling that the studies were stopped for most of the participants so that those in the comparison groups, which had been taking a medically worthless placebo, could instead receive AZT.
As a result, the FDA has been under increased pressure in recent months to formally expand the drug’s approved uses for the general public.
The decision, if enacted by the FDA, almost certainly will be welcomed by many physicians and AIDS advocacy groups, who have been pushing for such a change since the studies were announced with considerable fanfare last summer by federal health officials.
Although physicians are free to prescribe a drug any way they see fit once it has been approved for marketing, many have been reluctant to administer AZT for unapproved uses before the study data is available. In addition, many insurers will not pay for the drug unless it is prescribed for a use approved by the FDA.
In the months following announcement of the study results, many AIDS activists charged that thousands of patients around the country were being hurt, either because their doctors were giving them too much AZT, or in the case of infected patients without symptoms, no AZT at all.
Offering the first real evidence that AZT benefits patients with the beginning symptoms of infection, health officials announced last Aug. 3 that a study showed AZT “significantly” slows the progression of disease in patients with early AIDS-related complex, a finding they estimated could benefit 95,000 to 200,000 people.
Two weeks later, the government announced that the drug had been shown to delay the onset of the disease in infected individuals with T4-cell counts of less than 500. The study also tested AZT on infected individuals with more than 500 T4 cells, but the information was inconclusive and the research on that group is continuing.
The studies also showed that AZT was tolerated better by patients who received it early. Many individuals with fully developed AIDS have experienced toxic side effects from AZT.
If the FDA follows the panel recommendations, the decision could have an impact on about 600,000 of the estimated 1 million or more infected individuals in this country, federal health officials said.
