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Human Immunodeficiency Virus...
PEDIATRICS Vol. 112 No. 3 September 2003, pp. 679-684

EXPERIENCE AND REASON

Cognitive Decline With Immunologic and Virologic Stability in Four Children With Human Immunodeficiency Virus Disease

Mary Anne Toledo Tamula, MA and Pamela L. Wolters, PhD

HIV and AIDS Malignancy Branch
National Cancer Institute
National Institutes of Health
Bethesda, MD 20892
Medical Illness Counseling Center
Chevy Chase, MD 20815

Claire Walsek, RN, MS and Steven Zeichner, MD, PhD

HIV and AIDS Malignancy Branch
National Cancer Institute
National Institutes of Health
Bethesda, MD 20892

Lucy Civitello, MD

Children’s National Medical Center
Washington, DC 20010

This case series describes 4 children with vertically acquired human immunodeficiency virus (HIV) infection who exhibited immunologic, virologic, and clinical stability while on a protease inhibitor-containing highly active antiretroviral therapy (HAART) regimen, yet demonstrated significant cognitive decline as measured by standardized intelligence tests.

A retrospective review of 107 patient records of children with HIV infection on HAART treatment protocols was conducted. Four patients were identified who responded to protease inhibitor-containing HAART therapy with sustained viral load suppression, and stable immunologic and medical parameters, yet demonstrated significant cognitive decline. Such discordance between biological and clinical markers previously has been reported in adults with HIV disease but not in children. This observed decline in neurocognitive functioning despite stable medical parameters suggests that HAART regimens that are effective for systemic disease may not be as effective for the central nervous system (CNS), perhaps because the antiretrovirals do not penetrate adequately into the CNS.

Of note, 3 of these 4 patients did not have zidovudine (ZDV) included in their HAART regimen. The only patient who was treated with ZDV containing regimen received 90 mg/m2 every 6 hours, which is at the lower end of the recommended ZDV pediatric full-dose range (90 mg/m2 to 120 mg/m2). Two of the 4 patients began ZDV at 120 mg/m2 every 6 hours following the decline in their cognitive test scores and subsequently showed improved or stable functioning as evidenced by the results of follow-up psychometric testing.

Long-term prospective studies using both systemic and CNS measures are necessary to further investigate the effects of HAART in children with HIV disease. Longitudinal cognitive assessments of children receiving HAART appear indicated to identify cognitive decline and to provide appropriate therapeutic intervention when manifestations of HIV-related CNS disease progression occur.

Key Words: HIV • HAART

Abbreviations: HIV, human immunodeficiency virus • HAART, highly active antiretroviral therapy • CNS, central nervous system • ZDV, zidovudine • AIDS, acquired immunodeficiency syndrome • d4T, stavudine • NVP, nevirapine • CSF, cerebrospinal fluid • ddI, didanosine • NFV, nelfinavir • NCI, National Cancer Institute • IQ, intelligence quotient • CT, computed tomography • SD, standard deviation • GCI, General Cognitive Index • WISC-III, Wechsler Intelligence Scale for Children, Third Edition • FISQ, full-scale • intelligence quotient • VIQ, Verbal Intelligence Quotient • PIQ, Performance Intelligence Quotient • CDC, Centers for Disease Control and Prevention • NRTI, nucleoside reverse transcriptase inhibitor

Received for publication Nov 1, 2002; Accepted Mar 3, 2003.




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