MEDICINE / AIDS RESEARCH : Lower Doses of AZT Found Effective, Less Toxic
Low doses of the expensive AIDS drug AZT appear to be as effective as and less toxic than standard doses, according to two separate studies involving patients from California and across the country that are being published in today’s New England Journal of Medicine.
Publication of the studies is likely to encourage more AIDS physicians to recommend doses of AZT--azidothymidine--for their patients that are substantially lower than the doses of 1,200 to 1,500 milligrams a day that were common several years ago.
Many physicians already recommend lower doses, as the data supporting this approach has been publicized informally and at medical meetings.
“The standard of practice (today) is to use 500 to 600 milligrams a day,” said Dr. Harry Hollander, the chief AIDS physician at the UC Medical Center in San Francisco.
Hollander, who is not an author of either study, added that the major exception is for AIDS patients with nervous-system complications. It is not clear that low doses are effective for such patients.
Currently, Burroughs Wellcome Co., which manufactures AZT, recommends that AIDS patients be prescribed 200 milligrams of AZT every four hours for four weeks, and after that 100 milligrams of AZT every four hours. The basis for this recommendation is one of the New England Journal studies, whose primary author is Dr. Margaret A. Fischl of the University of Miami.
In a study of 524 patients, Fischl and her colleagues found that this level of daily doses of AZT “was at least as effective as a higher dose and was less toxic,” but that some patients still developed anemia, a common complication of the medicine.
The second study included 28 patients who received an even lower daily dose of AZT--50 milligrams every four hours. Most of the patients were treated for more than 40 weeks.
The research team, headed by Dr. Ann C. Collier of the University of Washington School of Medicine in Seattle, found that this very low dose had “clinical and virologic effects” similar to those of higher daily doses. They concluded that “the minimal effective dose” of AZT “has yet to be determined” and called for larger studies of the effects of 200 to 300 milligrams of AZT a day.
Hollander said the very low doses of AZT are likely to be most useful for patients who cannot tolerate 500 to 600 milligrams a day and for patients who are simultaneously taking experimental AIDS drugs. He cautioned that patients who receive very low doses of AZT may be at increased risk of developing drug-resistant strains of the AIDS virus.
The Burroughs Wellcome wholesale price for a 100-milligram capsule of AZT is $1.20. A 500-milligram daily dosage regimen should cost about $2,200 a year, the company said.
