The Duke Pediatric Aids Treatment Team has been engaged in clinical treatment trials for children with HIV infection since he all of 1986. Duke participated in the pediatric Phase I studies on zidovudine (ZDV), and has continued to treat the patients originally on that protocol. Patients (as many as five) have recently begun enrolling in the collaborative Phase II, open label (uncontrolled) study of zidovudine efficacy in children with AIDS (other than LIP alone) or severe ARC (<500 CD4+ cells). After enrollment in this study is full, an """"""""extension"""""""" will initiated, wherein additional qualifying patients can be enrolled in an identical protocol with separate analysis. Some patients in the extension will be randomized as to whether they will also receive intravenous immunoglobulin. Beginning in the near future, a collaborative Phase II, double-blind, placebo-controlled study of oral ZDV in children with LIP or ARC will open for enrollment. It is anticipated the Duke will be able to enroll 20-30 patients in this 2 year study. The final category of study in this proposal serves as the underpinning for three of the research projects (Projects 3, 4, and 5) in this application. Duke pediatrics will be participating in a Phase I study of I.V. and P.O. ZDV in newborn infants. After the conclusion of this study, which requires substantial amounts of blood for pharmaco kinetics, it is proposed to initiate a Phase II, double-blind, placebo-controlled study of neonatal prophylaxis using ZDV. If viral acquisition is a late gestational or perinatal event, the rapid use of ZDV may prevent virus acquisition. A short course of ZDV or placebo would be administered orally from immediately after birth, and the children followed intensively for one year. The intensive follow-up would be used to provide natural history information, as well as family/social intervention and evaluation. Because HIV transmission is only around 35-50% from infected mothers to infants, the double blind trial would have four populations: treated-infected, untreated-infected, treated-uninfected, and untreated-uninfected. Because of this design, accurate information separating disease from drug effects will be obtained. Special attention will be directed at areas of concern which have already been uncovered in studies to date: intellectual, social, and motor development; neurological sequelae of infection; cardiac disease (Project 2); renal disease; and dental development.
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