Zidovudine (AZT) therapy has reduced by two-thirds the risk of transmission of virus from HIV-infected pregnant women to their babies according to preliminary results of a trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), in collaboration with the National Institute of Child Health and Human Development (NICHD) and Institut National de la Sante et de la Recherche Medicale (INSERM) and Agence Nationale de Recherches sur le SIDA (ANRS) of France. Both NIAID and NICHD are part of the National Institutes of Health (NIH).
An interim review of the study, AIDS Clinical Trials Group (ACTG) Study 076, revealed a transmission rate of 8.3 percent when both mothers and their babies received AZT, in comparison with a transmission rate of 25.5 percent among those receiving a placebo.
Although this treatment did not protect all the babies in the study, the news that the risk of HIV transmission to newborns can be significantly reduced is very promising," says Donna E. Shalala, secretary of the U.S. Department of Health and Human Services (DHHS).
Anthony S. Fauci, M.D., NIAID director, stresses "Long-term follow up of all of the children born to mothers in this study is essential to learn more about the risks and benefits of the treatment beyond these encouraging early results."
An independent Data and Safety Monitoring Board (DSMB) reviewed the ACTG 076 preliminary findings. As a result of the DSMB's review and recommendations, the study investigators have stopped enrollment of women into ACTG 076 and are offering AZT to all currently enrolled pregnant women who remain in the study, as well as to their infants for the first 6 weeks of life. The study investigators plan to follow the infants for a number of years because the long-term consequences of AZT therapy are unknown; in addition. they will follow the women in trial for six months after delivery.
Researchers will monitor the growth and development and look for any unusual illnesses among the infants, according to the chairs of the ACTG 076 protocol Edward M. Connor, M.D., associate professor of pediatrics at the University of Medicine and Dentistry of New Jersey in Newark, and Rhoda Sperling, M.D., of the Department of Obstetrics and Gynecology at Mount Sinai School of Medicine.
Because long-term effects of therapy on the infants are currently unknown, no recommendations about treatment to prevent transmission of HIV during pregnancy and delivery are being made pending development of consensus on the balance between known benefit and unknown risk. In the meantime, more details about this study are included in a Clinical Alert to Physicians and in a Summary of ACTG 076 Findings. These documents are available from the AIDS Clinical Trials Information Service, 1-800-TRIALS-A. The ACTG 076 investigators are preparing a report of the study that will be submitted for publication to a peer-reviewed medical journal.
HIV is the fifth leading cause of death in U.S. children younger than 15 years, according to the National Center for Health Statistics. As of Sept. 30, 1993, the Centers for Disease Control and Prevention have received reports of 4,906 AIDS cases in children younger than 13 years. Of these children, 4,328 had a mother with, or at risk of having, HIV and 2,615 have died. Annually in the United States, an estimated 7,000 HIV-infected women give birth to infants, of which approximately 25 percent are HIV-infected.
ACTG 076 began in April 1991, with a target enrollment of 748 HIV-infected women in their 14th to 34th week of pregnancy who did not need AZT as part of their medical care. The women received either AZT or a placebo during pregnancy and labor. Neither the researchers nor the women knew to which treatment arm the women had been randomly assigned. The length of treatment ranged from one to 29 weeks, based on the time of the womens' enrollment.
Within 24 hours after birth and for six weeks thereafter, infants received the same treatment, either AZT or placebo, as their mothers.
The women received either a placebo or a standard adult dose of AZT during pregnancy. During labor, the women received a continuous intravenous dose of the placebo or AZT. The babies subsequently received a syrup of the placebo or of 2 mg/kg AZT four times a day for six weeks.
As of Dec. 20, 1993, 477 women had enrolled in the trial and 421 babies had been born. The results of at least one HIV culture test were available for 364 infants. Of these 364, 53 had HIV, of which 13 were born to mothers receiving AZT and 40 to mothers on placebo.
Investigators found that both mothers and infants tolerated the AZT treatment well, with no significant short-term side effects other than reversible mild anemia (low red blood cell counts) in some infants.
The women ranged in age from 15 to 43, averaging 25 years. Of the 463 women completing the trial, 50 percent were African- Americans and 29 percent were Hispanic. Of the 59 sites enrolling women into the trial, NIAID supported 35 and NICHD supported 15 in the United States; INSERM supported nine in France.
NIAID and NICHD, two of the 17 institutes at NIH, support scientists and scientific studies at universities, medical schools, hospitals and research institutions in the United States and abroad. NIH is an agency of the U.S. Public Health Service, part of DHHS. INSERM is the national biomedical research organization of France. Burroughs Wellcome Co. supplied the AZT for the study.