Reassuring Findings about Infants Exposed to Zidovudine

National Institute of Allergy and, Infectious DiseasesEMBARGOED FOR RELEASE, Tuesday, January 12, 1999, 4:00 p.m. EST, Laurie K. Doepel

Children exposed to zidovudine (ZDV, AZT) in utero and as newborns and who escaped acquiring HIV from their infected mothers show no cancers or other adverse health effects up through preschool age, according to a new study from the National Institutes of Health (NIH). It is the first report to assess the late effects of AZT exposure in healthy HIV-uninfected children born to mothers who took the drug to prevent transmitting HIV to their offspring.

The study, sponsored by the Pediatric AIDS Clinical Trials Group (PACTG) and funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Child Health and Human Development (NICHD), appears in the Jan. 13 issue of the Journal of the American Medical Association.

"These data are critically important because the current recommendation is to treat HIV-infected pregnant women with regimens that include AZT to prevent perinatal HIV transmission," says NIAID Director Anthony S. Fauci, M.D. "Although these findings are reassuring," he adds, "we need to continue to monitor these children for long-term adverse effects of the drug." The investigators plan to follow these children until at least age 21.

The 234 HIV-uninfected children evaluated in this report are part of PACTG 219, a long-term follow-up study that includes more than 2,200 children who have been enrolled in PACTG prevention and treatment protocols. The 234 children were born to mothers who participated in PACTG 076. This landmark NIH study showed that AZT can reduce HIV transmission from an infected woman to her infant by approximately two-thirds. The children in PACTG 076 were exposed to AZT or a placebo in utero and during labor and delivery, and also as newborns for six weeks.

The randomized design of PACTG 076 and subsequent follow-up in this study makes it easier to clearly evaluate AZT's potential toxicity, the investigators note. The health of children who received AZT (122 children) can be compared with that of a similar number of children (112) who received a placebo.

For the current study, the investigators evaluated the children at regular intervals. The main measures of interest included physical growth, cognitive and development milestones, immunologic function, cardiac and ophthalmologic evaluations, the occurrence of malignancies, and mortality.

"The good news is that there are no differences in growth and cognitive development between the children exposed to AZT versus the children who were not," comments lead author Mary Culnane, M.S., C.R.N.P, of NIAID's pediatric medicine branch in the Division of AIDS. "It also is reassuring that none of the children have developed cancers or died."

The JAMA article reports on data collected through February 1997. The median age of the children was 4.2 years (range 3.2 to 5.6 years). They continue to be followed in the PACTG clinics.

The authors conclude that their findings complement the earlier findings of PACTG 076, which found no evidence of AZT toxicity in children up to 18 months of age, and are consistent with the limited other early safety data concerning perinatal exposure to AZT. Future evaluations of these and other children in PACTG 219 will help define the long-term safety of AZT use during the perinatal period. Pediatric HIV specialists also hope to establish a registry to track the health of all children exposed to antiretrovirals, a proposal that is being actively discussed within the medical community.

NIAID and NICHD are components of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, malaria, asthma and allergies. NICHD supports and conducts basic, clinical and epidemiological research on the reproductive, developmental and behavioral processes that determine and maintain the health of children, adults, families and populations. NIH is an agency of the U.S. Department of Health and Human Services. Reference: M Culnane, MG Fowler, SS Lee, G McSherry, M Brady, K O'Donnell, L Mofenson, SL Gortmaker, DE Shapiro, G Scott, E Jimenez, EC Moore, C Diaz, PM Flynn, B Cunningham and J Oleske. Lack of long-term effects among uninfected children exposed to zidovudine. The Journal of the American Medical Association 281(2), 151-57 (1999).