Neurologic, neurocognitive, and brain growth outcomes in human immunodeficiency virus-infected children receiving different nucleoside antiretroviralregimens

Objectives. To compare the impact of three different nucleoside reverse tra nscriptase inhibitor regimens, zidovudine (ZDV) monotherapy, didanosine (dd I) monotherapy, and ZDV plus ddI combination therapy, on central nervous sy stem (CNS) outcomes in symptomatic human immunodeficiency virus (HIV)-infec ted children. Methods. Serial neurologic examinations, neurocognitive tests, and brain gr owth assessments (head circumference measurements and head computed tomogra phy or magnetic resonance imaging studies) were performed in 831 infants an d children who participated in a randomized double-blind clinical trial of nucleoside reverse transcriptase inhibitors. The Pediatric AIDS Clinical Tr ials Group study 152 conducted between 1991 and 1995 enrolled antiretrovira l therapy-naive children. Subjects were stratified by age (3 to <30 months of age or 30 months to 18 years of age) and randomized in equal proportions to the three treatment groups. Results. Combination ZDV and ddI therapy was superior to either ZDV or ddI monotherapy for most of the CNS outcomes evaluated. Treatment differences w ere observed within both age strata. ZDV monotherapy showed a modest statis tically significant improvement in cognitive performance compared with ddI monotherapy during the initial 24 weeks, but for subsequent protection agai nst CNS deterioration no clear difference was observed between the two mono therapy arms. Conclusions. Combination therapy with ZDV and ddI was more effective than e ither of the two monotherapies against CNS manifestations of human immunode ficiency virus disease. The results of this study did not indicate a long-t erm beneficial effect for ZDV monotherapy compared with ddI monotherapy.