Benefits of AZT Therapy Re-Evaluated

A group of investigators from the School of Public Health reported in today's issue of The New England Journal of Medicine that for some HIV-positive patients, quality-of-life considerations may outweigh the benefits of zidovudine (AZT) therapy.

AZT has proven effective in delaying the progression of AIDS, but it can cause fatigue, pain, fever and breathing difficulty in patients.

The study determined that because of these side effects, the drug should not be used by HIV-positive patients who are asympotmatic, meaning they have not yet developed AIDS-related symptoms.

When treated with AZT, 33 percent of these asymptomatic patients suffer severe and possibly life-threatening side effects, said study co-author Marcia A. Testa, lecturer on biostatistics at the School of Public Health.

"We hoped to see whether quality-of-life considerations would modify the decision to start taking AZT for asymptomatic patients," said William R. Lenderking, research associate in biostatistics at the School of Public Health and lead author of the study.

Testa said the study's focus on patients' quality of life was unusual, since most studies examine such factors as overall survival rates.

"We are not looking at biomedical markers," she said, "but markers that are important to living on a day-today basis."

The investigators reanalyzed the same data that originally established the effectiveness of AZT in delaying the progression of AIDS.

Recent studies have confirmed that AZT does not actually add length to the life of asymptomatic patients, but may postpone the onset of the disease for a small amount of time, Testa said.

"If you could postpone something for a week, would you suffer the side effects for 5 years?" she asked.

The drug is also limited because patients develop resistance to its effects, Testa said.

"If you give AZT early on," said Testa, "people become resistant and you can't give it later on (when the patient has developed serious AIDS-related symptoms)."

"The bottom line is there's a limited benefit associated with AZT." said Lenderking. "The question is, do you want to take the benefit when you're asymptomatic or wait until you have the symptoms?"

But Dr. Martin S. Hirsch, professor of medicine at the medical school and director of AIDS research at Massachusetts General Hospital, said the study's results are not necessarily definitive.

"I think what the study reported is valid, but it's not the final answer to the question," he said. "We have to always be willing to keep an open mind as to the chaning nature of the infection and the drugs we have available."

The study's focus on AZT is already limited because other treatments were developed after the research was done for the study, he said.

"What is different now from what was the case when the study was done, is that we have other alternatives for treatments if a patient develops AZT resistance," he said.

Didanosine (DDI) is currently being used for patients who have developed AZT resistance, Hirsch said patients, Lederking defended the study's focus on AZT.

DDI is not as effective as AZT, which is still the most widely-used treatment, Lederking said.

Prominent AIDS researcher Dr. Samuel A. Bozzette, professor of medicine at the UC-San Diego School of Medicine, said the study will help physicians and their patients to make informed decisions about the use of AZT.