A federally financed study has found that the drug AZT drastically reduces transmission of H.I.V., the virus that causes AIDS, from infected mothers to their newborns, Government health officials said today.
The findings were considered so significant that the study, which began in April 1991, was ordered stopped on Friday, and officials are spending the holiday weekend notifying the 59 medical centers in the United States and France taking part in the study to offer AZT to the pregnant women who had been receiving a placebo.
In addition, said Dr. Anthony S. Fauci, the head of the National Institute of Allergy and Infectious Diseases, the data from the study were being distributed as a "clinic alert" through the National Library of Medicine, which has a computer network available to health care workers around the world.
Dr. Harold W. Jaffe, an epidemiologist and the top scientist on H.I.V. at the Centers for Disease Control and Prevention in Atlanta, said in an interview today that the finding was one "of major public health importance."
"It is the first indication that mother-to-child transmission of H.I.V. can be at least decreased, if not prevented," Dr. Jaffe said. "And it will provide a real impetus for identifying more H.I.V.-infected women during pregnancies so that they could consider the benefit of AZT treatment to themselves and their children."
About four million women give birth in the United States each year, and the disease centers estimate that 6,000 to 7,000 of them are H.I.V.-infected. About 1,500 to 2,000 of their babies later become H.I.V.-infected.
Big Problem in Africa
The transmission of the virus to newborns is a much bigger public health problem in developing countries in Africa, Asia and South America, where millions of people are infected and where infection rates among childbearing women can reach 10 percent to 30 percent in some areas, said Dr. James Curran, coordinator of all H.I.V. activities at the disease centers. He added that in some areas of the United States, including some urban areas in the Northeast, the comparable figure is as high as 5 percent.
On average, about 25 percent of pregnant women who are H.I.V.-infected pass along the virus to their babies. The researchers had confidence in the study because the difference in results was so marked. The study found that 26 percent of newborns whose mothers had received a placebo during pregnancy were infected. But the infection rate was only 8 percent for those whose mothers received AZT, officials said. All the babies were also given AZT after birth.
The officials said that they could find no difference in the number and type of birth defects in babies whose mothers received AZT or the placebo. They added that there had been no significant health hazard among the children during the first 18-month follow-up period.
"This is a real breakthrough and it has worldwide implications," Dr. Curran said.
The development is another strange twist in the up-and-down reputation of AZT.
The drug has been shown to delay the progression from H.I.V. infection to full-scale AIDS, although experience has shown that the benefit generally wanes after a year or two. But Dr. Fauci said that the finite period of pregnancy may allow AZT to reduce the risk of transmission to newborns.
The start of the new study was delayed by debates over the ethics. Among the questions raised by critics was whether many uninfected fetuses would be subject to possible hazards from AZT.
The new findings raise major practical and ethical questions. Until now, testing for H.I.V. infection in the United States has been recommended for those who consider themselves at risk. But testing is not mandatory, and there is no general recommendation to test all pregnant women. The American Academy of Pediatrics recommends testing of pregnant women in areas where the prevalence of H.I.V. is high. But compliance among health officials varies.
The new study offers impetus for more aggressive testing programs for pregnant women because of the benefits of the AZT treatment. But any calls for mandatory tests would raise the issue of a woman's right to privacy. In addition, developing countries would face the issue of paying for the drug.
"There needs to be a clear, immediate re-thinking of recommendations for treatment of H.I.V. during pregnancy and guidelines given to infected mothers so that they can choose appropriately," Dr. Curran said.
Dr. Curran and Dr. Fauci said that they expected the Government to convene a group of experts as soon as possible to discuss general recommendations about testing and treating pregnant women. One important issue will be to follow the infants to be sure no problems arise when they grow older, the doctors said.
The study involved 477 H.I.V.-infected women at 50 medical centers in the United States and nine in France who enrolled during their 14th to 34th week of pregnancy. The women had more than 200 CD-4 cells per cubic millimeter in their blood, so that there was no specific reason for them to take AZT, according to standard guidelines. A count of CD-4 cells is a measure of the health of the immune system.
Newborns Also Given AZT
The women agreed to receive either AZT or placebos during pregnancy and labor. According to the standard design of scientific studies, the choice of drug or placebo was determined by lot and neither the patients nor the doctors knew who was getting which. As the women went into labor, the pills were stopped and the drug or placebo was injected by vein until the baby was born.
Each newborn then received AZT in a syrup for six weeks. The infants were tested at regular intervals for 18 months. The tests included standard H.I.V. tests and blood samples that were cultured in the laboratory to grow H.I.V.
The 477 women in the study gave birth to 421 babies. Of the 364 babies for whom at least one culture test was available, 53 had become H.I.V.-infected. Of the 53, 40 were born to mothers who received placebos and 13 were born to mothers who received AZT.
Findings Raise Questions
The new findings raise many questions that experts in health policy will need to answer. These are among them:
*Which women ought to be tested for H.I.V. infection?
*How often should a woman be tested during pregnancy?
*Which women should be offered therapy?
*How should an infected mother and infant be treated in cases where the mother has received no prenatal care? Is there still a benefit to giving AZT to a newborn infant even if the mother did not receive it during pregnancy?
The study did not discuss the benefits of AZT therapy for women who had AIDS or with CD-4 cell counts lower than 200. Scientists know that H.I.V. transmission rates go up as the CD-4 count drops. So another question that needs to be answered is how much benefit there is for a child born to a woman with a low CD-4 count.
An article on Friday about a New York State advisory panel's rejection of a proposal to test newborns for the virus repeated the error in some editions.