Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women. Pediatric AIDS Clinical Trials Group Protocol 219/076 Teams

JAMA. 1999 Jan 13;281(2):151-7. doi: 10.1001/jama.281.2.151.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes
  • Child Development
  • Child, Preschool
  • Echocardiography
  • Female
  • Growth
  • HIV Infections / drug therapy
  • HIV Infections / prevention & control*
  • HIV Infections / transmission
  • Humans
  • Infant
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical / prevention & control*
  • Longitudinal Studies
  • Male
  • Pregnancy
  • Pregnancy Complications, Infectious / drug therapy
  • Pregnancy Complications, Infectious / prevention & control*
  • Pregnancy Outcome
  • Prenatal Exposure Delayed Effects*
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Vision Tests
  • Zidovudine / therapeutic use*


  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors
  • Zidovudine