Health Officials May Replace Azt With Ddi As First-Line Aids Drug
After years of recommending AZT as the first-line drug for treating the virus that causes AIDS, federal health officials are considering a change because of surprising results with other drugs.
Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases, said in an interview that he planned to convene a meeting where independent experts could decide whether AZT should remain the first choice.
A large study paid for by Fauci’s institute and reported last week found that AZT was less effective than another drug, didanosine, or ddI, and also less effective than combinations of AZT with either ddI or zalcitabine (ddC).
One part of the study showed that ddI lowered the rate of death from HIV infection to 5 percent from 10 percent when compared with the use of AZT alone over 147 weeks.
The study provided the first conclusive evidence that a drug could reduce the risk of death in symptomless people who are at an intermediate stage of infection with HIV, Fauci said.
Two similar independent studies are due to be completed by January. One is being conducted in the United States, the other in Europe and Australia.
Fauci said he would ask the meeting of experts to review the findings of all three studies and consider whether a change in recommendations for the treatment of HIV was needed.
Two AIDS experts who participated in the study that was reported last week, Dr. Paul Volberding of San Francisco General Hospital and Dr. Fred T. Valentine of New York University Medical Center, joined Fauci in calling the findings important.
David Barr, the director of treatment education at the Gay Men’s Health Crisis in New York City, said that “The way ddI stands out has taken everyone by surprise.”
“It suggests,” Barr said, “that ddI is a better single drug to start with than AZT. But it does not answer the question whether ddI is better than nothing.”
Indeed, Fauci and other experts confirmed that ddI had never been compared with a placebo in a large study, even the one now being reported, whereas AZT had proved better than a placebo in earlier studies.
Barr said the Gay Men’s Health Crisis would withhold judgment on the new study’s findings until completion of an independent statistical analysis. New calculations are needed, he said, because of the large amount of data involved in the study and his organization’s concern that problems had arisen with statistical analyses of earlier federally sponsored studies.
One point of concern, Barr said, is the unusually large dropout rate - 53 percent of the 2,500 people who began as subjects in the study did not complete it - and that rate’s effect on the statistical power of the study.
Federal health officials said the high dropout rate reflected adverse reactions to the drugs, disease progression and the study’s demands on patients. A federal analysis said that “the premature withdrawal rate may have diluted the power to detect differences but does not appear to have negated the results and conclusions.”< The study was carried out at 52 medical centers in the United States. It involved infected patients whose immune system had been moderately impaired by HIV and who had CD4 counts from 200 to 500. CD4 cells are the prime target of HIV, and CD4 counts are a standard measure of immune system function. The normal count is 800 to 1,200.
The participants were randomly divided into four groups, which received AZT alone, ddI alone, a combination of ddI and AZT, or a combination of ddC and AZT.
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