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