Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women

Context With the success of zidovudine chemoprophylaxis for prevention of p erinatal transmission of the human immunodeficiency virus (HIV), an increas ing number of HIV-exposed but uninfected children will have in utero exposu re to zidovudine and other antiretroviral drugs. Objective To evaluate the long-term effects of in utero exposure to zidovud ine vs placebo among a randomized cohort of uninfected children. Design Prospective cohort study based on data collected during Pediatric AI DS Clinical Trials Group Protocol 076, a perinatal zidovudine HIV preventio n 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-infect ed 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 d ata assessed every 6 months for children younger than 24 months and yearly thereafter or as clinically indicated. Baseline echocardiogram and fundusco pic evaluations were collected before 36 months of age. Results Median age of children at time of last follow-up visit was 4.2 year s (range, 3.2-5.6 years). There were no significant differences between chi ldren exposed to zidovudine and those who received placebo in terms of sequ ential data on lymphocyte subsets; weight, height, and head circumference z scores; and cognitive/ developmental function. No deaths or malignancies o ccurred. Two children (both exposed to zidovudine) are being followed up fo r abnormal, unexplained ophthalmic findings. One child exposed to zidovudin e 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 wit h in utero and neonatal exposure to zidovudine followed up for as long as 5 .6 years. Continued prospective evaluations of children born to HIV-infeded women who are exposed to antiretroviral or immunotherapeutic agents are cr itical to assess the longterm safety of interventions that prevent perinata l HIV transmission.