Background and Methods. Zidovudine has been shown to be an effective antiretroviral treatment in adults with human immunodeficiency virus (HIV) infection. We examined the safety of zidovudine and the tolerance of and therapeutic response to the drug in 88 children with advanced HIV disease. During a 24-week outpatient trial, zidovudine (180 mg per square meter of body-surface area per dose) was given by mouth every six hours and serial measurements were made of clinical, immunologic, and virologic indexes. Children who completed 24 weeks of treatment were permitted to continue receiving zidovudine. Results. Of the 88 children (mean age, 3.9 years; range, 4 months to 11 years), 61 completed the initial 24-week trial, and 49 continued to receive zidovudine for up to 90 weeks (median follow-up, 56 weeks). The patients generally tolerated zidovudine well. One or more episodes of hematologic toxicity occurred in 54 children (61 percent) - anemia (hemoglobin level, <75 g per liter) in 23 children (26 percent) and neutropenia (neutrophil count, <0.75×109 per liter) in 42 (48 percent). Many of these abnormalities resolved spontaneously, but 30 children required transfusions or a modification of the dose of zidovudine. Only three children had to stop receiving the drug because of hematologic toxicity. Kaplan-Meier analysis demonstrated that the probability of survival was 0.89 after 24 weeks and 0.79 after 52 weeks. There was marked improvement in weight gain, cognitive function (mainly in children <3 years old), serum and cerebrospinal fluid concentrations of p24 antigen, and the proportion of cerebrospinal fluid cultures negative for HIV. CD4+ lymphocyte counts (mean at base line, 0.263×109 per liter) improved during the first 12 weeks, although the improvement was not sustained through the 24th week. Conclusions. Zidovudine in a dose of 180 mg per square meter every six hours can be safely administered to children with advanced HIV disease. The resultant clinical, immunologic, and virologic improvements in children are similar to those reported with zidovudine in adults.
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