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Mary Culnane, MS CRNP; MaryGlenn Fowler, MD MPH; Sophia S. Lee, MS; George McSherry, MD; Michael Brady, MD; Karen O'Donnell, PhD; Lynne Mofenson, MD; Steven L. Gortmaker, PhD; David E. Shapiro, PhD; Gwendolyn Scott, MD; Eleanor Jimenez, MD; Ellen C. Moore, MD; Clemente Diaz, MD; Patricia M. Flynn, MD; Bethann Cunningham, MS; James Oleske, MD MPH; for the Pediatric AIDS Clinical Trials Group Protocol 219/076 Teams

JAMA. 1999;281:151-157.

Context  With the success of zidovudine chemoprophylaxis for prevention of perinatal transmission of the human immunodeficiency virus (HIV), an increasing number of HIV-exposed but uninfected children will have in utero exposure to zidovudine and other antiretroviral drugs.

Objective  To evaluate the long-term effects of in utero exposure to zidovudine vs placebo among a randomized cohort of uninfected children.

Design  Prospective cohort study based on data collected during Pediatric AIDS Clinical Trials Group Protocol 076, a perinatal zidovudine HIV prevention trial, and Protocol 219, a long-term observational protocol.

Setting  Pediatric research clinics in the United States.

Patients  Two hundred thirty-four uninfected children born to 230 HIV-infected women enrolled in Protocol 076 and followed up through February 28, 1997, in Protocol 219 (122 in the zidovudine group and 112 in the placebo group).

Main Outcome Measures  Physical growth measurements, immunologic parameters, cognitive/developmental function, occurrence of neoplasms, and mortality data assessed every 6 months for children younger than 24 months and yearly thereafter or as clinically indicated. Baseline echocardiogram and funduscopic evaluations were collected before 36 months of age.

Results  Median age of children at time of last follow-up visit was 4.2 years (range, 3.2-5.6 years). There were no significant differences between children exposed to zidovudine and those who received placebo in terms of sequential data on lymphocyte subsets; weight, height, and head circumference z scores; and cognitive/developmental function. No deaths or malignancies occurred. Two children (both exposed to zidovudine) are being followed up for abnormal, unexplained ophthalmic findings. One child exposed to zidovudine had a mild cardiomyopathy on echocardiogram at the age of 48 months; the child is clinically asymptomatic.

Conclusions  No adverse effects were observed in HIV-uninfected children with in utero and neonatal exposure to zidovudine followed up for as long as 5.6 years. Continued prospective evaluations of children born to HIV-infected women who are exposed to antiretroviral or immunotherapeutic agents are critical to assess the long-term safety of interventions that prevent perinatal HIV transmission.

Author Affiliations: Pediatric Medicine Branch (Ms Culnane) and Efficacy Trials Branch (Dr Fowler), Division of AIDS, National Institute of Allergy and Infectious Diseases, and the Pediatric, Adolescent and Maternal AIDS Branch, National Institute of Child Health and Human Development (Dr Mofenson), National Institutes of Health, Bethesda, Md; Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Mass (Ms Lee and Drs Gortmaker and Shapiro); Department of Pediatrics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark (Drs McSherry and Oleske); Section of Infectious Diseases, Columbus Children's Hospital, Ohio State University, Columbus (Dr Brady); Department of Pediatrics, Duke University Medical Center, Durham, NC (Dr O'Donnell); Department of Pediatrics, University of Miami School of Medicine, Miami, Fla (Dr Scott); Departments of Pediatrics, San Juan City Hospital (Dr Jimenez) and School of Medicine, University of Puerto Rico (Dr Diaz), San Juan; Department of Pediatrics, Wayne State University, Detroit, Mich (Dr Moore); Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, Tenn (Dr Flynn); and the Frontier Science and Technology Research Foundation, Amherst, NY (Ms Cunningham).

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