Published online February 12, 2007
PEDIATRICS Vol. 119 No. 3 March 2007, pp. e681-e693 (doi:10.1542/peds.2006-1145)
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ARTICLE

Neurodevelopmental Functioning in HIV-Infected Infants and Young Children Before and After the Introduction of Protease Inhibitor–Based Highly Active Antiretroviral Therapy

Jane C. Lindsey, ScDa, Kathleen M. Malee, PhDb, Pim Brouwers, PhDc, Michael D. Hughes, PhDa for the PACTG 219C Study Team

a Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts
b Chicago Children's Memorial Hospital, Northwestern University, Chicago, Illinois
c Center for Mental Health Research on AIDS, National Institute of Mental Health, National Institutes of Health, Rockville, Maryland

OBJECTIVES. The purpose of this work was to examine the effects of HIV infection and the impact of highly active antiretroviral treatment with protease inhibitors on neurodevelopmental functioning during the first 3 years of life.

PATIENTS AND METHODS. Pediatric AIDS Clinical Trials Group 219/219C is a longitudinal cohort study that has enrolled HIV-infected (HIV+) and HIV-exposed but uninfected (HIV–) infants and children since 1993. Longitudinal profiles of neurodevelopmental functioning as measured by the Bayley Scales of Infant Development were compared by HIV-infection status before and after the availability of highly active antiretroviral therapy with a protease inhibitor and within infants with Bayley tests available before and after initiating protease inhibitor therapy.

RESULTS. In the pre–protease inhibitor era, mean mental and motor scores in HIV+ (n = 54) infants <1 year of age were significantly lower than those among HIV– infants (n = 221) and remained lower up to 2 years of age. After protease inhibitors became available, mean mental and motor functioning of HIV+ infants (n = 91) <1 year of age were still significantly lower than those of HIV– infants (n = 838). However, against a background of declining scores among the HIV– infants, there was evidence of limited improvement in the HIV+ infants relative to their uninfected peers. Among infants who had Bayley II evaluations before and after starting a protease inhibitor, there was a trend to improved mental and motor scores after initiation of protease inhibitor therapy.

CONCLUSIONS. The suppression of systemic viral replication and subsequent substantial improvements in survival and immunologic status brought about by highly active antiretroviral therapy have been followed by limited improvements in neurodevelopmental functioning in young children. Additional longitudinal research is needed to better understand the role of antiretroviral therapy as well as the impact of genetic and environmental factors on neurodevelopmental functioning in children affected by HIV.

Key Words: HIV • neurodevelopmental functioning • cohort study

Abbreviations: CNS—central nervous system • HIV+—HIV-infected • HAART—highly active antiretroviral therapy • PI—protease inhibitor • HIV–—HIV-exposed but uninfected • PACTG—Pediatric AIDS Clinical Trials Group • ART—antiretroviral therapy • B-I—Bayley Scales of Infant Development • B-II—Bayley Scales of Infant Development, Second Edition • CDC—Centers for Disease Control and Prevention • GEE—generalized estimating equation • NRTI—nucleotide reverse transcriptase inhibitor

Accepted Sep 28, 2006.


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