Published online February 1, 2005
PEDIATRICS Vol. 115 No. 2 February 2005, pp. 380-387 (doi:10.1542/10.1542/peds.2004-1108)
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Neuropsychological Functioning and Viral Load in Stable Antiretroviral Therapy-Experienced HIV-Infected Children

Rita J. Jeremy, PhD*, Soyeon Kim, ScD{ddagger}, Molly Nozyce, PhD§, Sharon Nachman, MD||, Kenneth McIntosh, MD, Stephen I. Pelton, MD#, Ram Yogev, MD**, Andrew Wiznia, MD{ddagger}{ddagger}, George M. Johnson, MD§§, Paul Krogstad, MD||||, Kenneth Stanley, PhD{ddagger} for the Pediatric AIDS Clinical Trials Group (PACTG) 338 & 377 Study Teams

* Pediatric Clinical Research Center, Department of Pediatrics, School of Medicine, University of California, San Francisco, California
{ddagger} Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts
§ Neurodevelopmental Service, Jacobi Medical Center, Bronx, New York
|| Department of Pediatrics, State University of New York Health Science Center, Stony Brook, New York
Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts
# Boston Medical Center, Boston, Massachusetts
** Children's Memorial Hospital and Northwestern University School of Medicine, Chicago, Illinois
{ddagger}{ddagger} Department of Pediatrics, Jacobi Medical Center and Albert Einstein College of Medicine, Bronx, New York
§§ Pediatric Infectious Diseases, Medical University of South Carolina, Charleston, South Carolina
|||| Departments of Pediatrics and Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California

Objective. Neuropsychological functioning and its correlation with viral load were investigated for previously treated HIV-infected children who underwent a change in treatment regimen.

Methods. Thirteen age-appropriate measures of cognitive, neurologic, and behavioral functioning were administered to 489 HIV-infected children who were aged 4 months to 17 years and had been treated previously for at least 16 weeks with antiretroviral therapy. These clinically and immunologically stable children were randomized onto 1 of 7 drug treatment combinations, 6 of which included a protease inhibitor (PI), and evaluated prospectively for 48 weeks with respect to changes in neuropsychological performance and viral load.

Results. Neuropsychological functioning was significantly poorer at baseline for the HIV-infected children as compared with established norms for their age. Children with higher viral load had poorer cognitive, both-hands fine-motor, and neurologic signs at baseline, but single-hand fine-motor and behavioral functioning were not correlated with viral load. After 48 weeks of treatment with PI-containing combination therapy, there was significant improvement in only the vocabulary score. Neuropsychological changes did not differ among the 6 PI-containing combination regimens. At week 48, even children with a viral load response below the level of detection (RNA ≤400 copies/mL) still showed poorer neuropsychological functioning compared with established norms.

Conclusion. Poor neuropsychological functioning was seen for HIV-infected children and was worse for children with higher viral loads. Only 1 measure of neuropsychological functioning showed improvement after treatment with PI-containing combination therapy, and the extent of that improvement was relatively minor. Treatment strategies for children with HIV disease need to be reevaluated so that they consider restoration of neuropsychological functioning in addition to lowering the viral load.

Key Words: HIV • child • neuropsychological tests • cognitive science • neurologic examination • behavior • antiretroviral agents • protease inhibitors

Abbreviations: CNS, central nervous system • NP, neuropsychological • ZDV, zidovudine • ddI, didanosine • PI, protease inhibitor • PACTG, Pediatric AIDS Clinical Trials Group • CDC, Centers for Disease Control and Prevention • NRTI, nucleoside reverse transcriptase inhibitor • 3TC, lamivudine • d4T, stavudine • RTV, ritonavir • NVP, nevirapine • NFV, nelfinavir • MDI, Mental Development Index • FSIQ, Full Scale Intelligence Quotient • STM, Short-Term Memory • CI, confidence interval

Accepted Jul 19, 2004.


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