A Study of Azidothymidine in HIV-Infected Children

One of the most serious effects of HIV disease in children is neuropsychological deterioration (relating to mental and nervous system functioning). This complication affects the vast majority of HIV infected children. A previous study of continuous intravenous administration of AZT in pediatric patients with HIV infection showed consistent and dramatic improvements of symptoms in all patients that had shown neurodevelopmental deficits or abnormalities. These improvements were seen within 3 to 4 weeks after AZT treatment was started. Neurodevelopmental improvements have been sustained on AZT, usually showing steady improvement which, in some patients, was associated with restoration of pre-HIV intellectual and neurological function. This study also showed an increase in the IQ scores of children receiving continuous infusion of AZT who did not have overt clinical evidence of encephalopathy (disease of the brain). Thus changes in cognitive function may be among the earliest signs of AIDS encephalopathy and underscores the need to start therapies that will treat the central nervous system in patients who appear to be clinically intact. A study comparing continuous infusion to intermittent dosing of AZT showed a significant increase in IQ scores for those children receiving the continuous dose compared to those treated with the intermittent schedule. Although a portable infusion pump allows patients to receive continuous infusion of AZT, a sustained release oral formulation that could provide a continuous release of AZT into the bloodstream would be highly desirable. AMENDED 07/07/93: Children with progressive encephalopathy who have received a minimum of 3 months of oral or intermittent AZT or who have failed to improve following 6 months of optimal AZT will receive continuous infusion AZT via a portable infusion pump. AMENDED: The oral sustained release has been dropped and is now oral ddI. Added has been a planned stratification for randomization for patients who received any antiretroviral therapy 4 or more weeks prior to study entry. The informed consent was modified to reflect ddI toxicities from adult studies. Computerized Tomography radiation dosimetry is now included. AMENDED: Dropping the ddI component and open only to children with encephalopathy meaning they are losing milestones, this is equal to a P2 CDC rating . Testing the difference in intermediate vs continuous AZT. 12/1990. Original design: Children are first evaluated for randomization according to whether they have or do not have evidence of neurodevelopmental deficits at the time of the initial pretreatment evaluation. Patients are assigned to 1 of 3 groups, to receive AZT (1) by continuous infusion; (2) by oral, intermittent (every 6 hours) dosing; or (3) by oral sustained-release dosing. If the oral sustained-release formulation is not available when this study begins, it will begin with only the first 2 groups. The sustained release preparation will be evaluated as soon as it is available. Patients will be tested to measure physical or biological improvement in neurodevelopmental function.