Scientists to Test Drug AZT on Pregnant AIDS Patients; UCLA Among Facilities

Scientists will begin testing the AIDS drug AZT in infected pregnant women to determine whether the drug can prevent transmission of the virus to the fetus, federal health officials announced Monday.

The research is considered unusual because medical practice traditionally dictates that pregnant women avoid taking drugs whenever possible. Few drugs have been studied in pregnant women in the past unless the potential benefits far outweighed the potential risks.

More than 1,600 cases of AIDS in children have been reported since the deadly disease was first identified in 1981, and at least two or three times that many children are estimated to be infected with human immunodeficiency virus, which causes AIDS, according to the National Institute of Allergy and Infectious Diseases.

Some of these children were infected through the transfusion of contaminated blood or blood products but more than 80% got the virus from their mother during pregnancy. “Their numbers are rising steeply,” the agency said.

“The prognosis for children with (AIDS) is grim,” said Dr. Anthony S. Fauci, director of the institute, which is sponsoring the study. “They usually develop the disease more quickly than adults do. Of those diagnosed before their first birthday, half die within six months of diagnosis. It is impossible to count the costs in pain and heartbreak, and the social and economic burden of caring for these children is staggering.”

The study, which will examine only the safety of the drug in pregnant women, will be conducted at the UCLA School of Medicine and at the University of Miami.

“It’s very important as a first step to see if we can do something about perinatal transmission of HIV,” said Dr. Yvonne Bryson, who will direct the UCLA research.

Researchers long have been baffled by the mechanism of transmission between mother and fetus, although they believe that it occurs in one of three ways--either through the placenta in the uterus; at birth, through contact with or ingestion of the mother’s infected blood, or, less frequently, through breast milk.

Fauci’s agency has estimated the risk of transmission at between 25% and 40%, although some researchers have said that it could be as high as 60%.

Also, it is difficult to determine whether an infant actually has been infected until the child reaches the age of about 15 months, since children carry antibodies passed on by their mothers until that time and do not develop their own antibodies until later. Thus, the standard test for AIDS infection--which measures antibodies present in the blood--is not considered reliable in newborns.

AZT, or zidovudine, is the only AIDS drug approved to treat the underlying viral condition. It has been shown to significantly prolong life in AIDS patients, although it has also demonstrated toxic side effects in some individuals. Some studies on pregnant mice have shown that AZT has a beneficial effect in preventing the transmission of leukemia into the womb.

Initial reaction to the study among medical ethicists appeared favorable, although most asserted that it is essential pregnant women who decide to participate be fully informed.

“I think, in this case, the list of risks is substantial, but the list of potential benefits is, too,” said Dr. June Osborn, dean of the school of public health at the University of Michigan and a member of the World Health Organization’s global AIDS commission.

“Often, when you’re using drugs with pregnant women, the fetus has nothing to gain and everything to lose,” she added. “But here, you’ve got both fetus and mother with the substantial theoretical likelihood of benefit--with both fetus and mother having a lot to lose in the natural situation.”

Dr. Bernard Lo, professor of medicine and medical ethics at UC San Francisco, agreed.

“I think there is tremendous potential benefit as well as the possibility of substantial risk,” he said. “But as long as the study is designed to minimize risk, it’s an ethical study. In fact, it may be unethical to not intervene in what is a potentially disastrous situation for the child.”

The National Institute of Allergy and Infectious Diseases said that all women in the study will begin receiving AZT during their third trimester of pregnancy, when fetal organs are already formed and there is less danger of the drug causing deformities. “The baby is fully formed at 56 days, so that we don’t feel that there is any chance of toxicity with the drug,” Bryson said.

Also, she said, in some limited instances around the country, pregnant women have already received AZT, with no ill effects for their babies. “This gives us some reassurance,” she said.

Some studies have suggested that pregnancy accelerates the development of AIDS in infected women, or worsens the disease.

The majority of infants with HIV infection are born to women who are either intravenous drug users or sexual partners of intravenous drug users, the institute said. Thus, the agency said, one part of the study will address whether AZT can be safely given to infected pregnant women with a history of drug abuse, or who are on methadone maintenance. Methadone is a medically approved drug widely used in heroin-abuse rehabilitation.