In a randomized controlled trial of zidovudine (ZDV), didanosine (DDI) or combination ZDV+DDI therapy conducted in 831 HIV-infected infants and children(ACTG Protocol 152), neurologic examinations and neuropsychological/neurocognitive tests were performed according to an age-appropriate schedule. Neuroimaging of the head (CT/MRI) was performed at entry and after 96 weeks. Clinical HIV disease progression due to neurologic deterioration, decline in neurocognitive performance, or increasing cortical atrophy was an important primary end point in this study. Additional analyses have been conducted to specifically assess the impact of different antiretroviral therapies on outcomes related to the developing central nervous system. Analysis of neurocognitive scores demonstrated significant improvements from baseline after 96 weeks of therapy in children who received ZDV+DDI compared with those who received ZDV. No significant differences were seen overall between DDI and ZDV, or between DDI and ZDV+DDI recipients. A preplanned subgroup analysis of children 3-30 months of age who were assessed using the Bayley Scales of Infant Development showed marginally significant improvements for both ZDV (P=0.066) and ZDV+DDI (P=0.045) groups compared with the DDI group in the initial 24 weeks. Analysis of neuroimaging studies showed a significantly higher proportion of children randomized to ZDV with increased cortical atrophy at 96 weeks compared to ZDV+DDI recipients; no significant differences were seen between DDI and ZDV recipients or between DDI and ZDV+DDI recipients.

CONCLUSION: After 96 weeks of therapy, combination ZDV+DDI recipients showed a significantly better increase in cognitive scores from baseline and less cortical atrophy compared with ZDV recipients. A subgroup analysis of neurocognitive scores in younger children suggested an initial benefit of ZDV+DDI compared with DDI alone.