Neurologic, neurocognitive, and brain growth outcomes in human immunodeficiency virus-infected children receiving different nucleoside antiretroviral regimens. Pediatric AIDS Clinical Trials Group 152 Study Team.
OBJECTIVE
To compare the impact of three different nucleoside reverse transcriptase inhibitor regimens, zidovudine (ZDV) monotherapy, didanosine (ddI) monotherapy, and ZDV plus ddI combination therapy, on central nervous system (CNS) outcomes in symptomatic human immunodeficiency virus (HIV)-infected children.


METHODS
Serial neurologic examinations, neurocognitive tests, and brain growth assessments (head circumference measurements and head computed tomography or magnetic resonance imaging studies) were performed in 831 infants and children who participated in a randomized double-blind clinical trial of nucleoside reverse transcriptase inhibitors. The Pediatric AIDS Clinical Trials Group study 152 conducted between 1991 and 1995 enrolled antiretroviral 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 were observed within both age strata. ZDV monotherapy showed a modest statistically significant improvement in cognitive performance compared with ddI monotherapy during the initial 24 weeks, but for subsequent protection against CNS deterioration no clear difference was observed between the two monotherapy arms.


CONCLUSIONS
Combination therapy with ZDV and ddI was more effective than either of the two monotherapies against CNS manifestations of human immunodeficiency virus disease. The results of this study did not indicate a long-term beneficial effect for ZDV monotherapy compared with ddI monotherapy.
Raskino
C
C
Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts 02115, USA. raskino@sdac.harvard.edu
Pearson
D A
DA
Baker
C J
CJ
Lifschitz
M H
MH
O'Donnell
K
K
Mintz
M
M
Nozyce
M
M
Brouwers
P
P
McKinney
R E
RE
Jimenez
E
E
Englund
J A
JA
D000293:Adolescent; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001921:Brain / Q000254:growth & development*; D002493:Central Nervous System Diseases / Q000209:etiology / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects*; D016049:Didanosine / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007361:Intelligence Tests; D008297:Male; D009048:Motor Skills / Q000187:drug effects*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D015215:Zidovudine / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D016049:Didanosine