title: Cognitive decline with immunologic and virologic stability in four children with human immunodeficiency virus disease.
abstract: 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/m(2) every 6 hours, which is at the lower end of the recommended ZDV pediatric full-dose range (90 mg/m(2) to 120 mg/m(2)). Two of the 4 patients began ZDV at 120 mg/m(2) 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.
authors.affiliation: HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1868, USA. tamulam@mail.nih.gov
authors.forename: Mary Anne Toledo
authors.initials: MA
authors.lastname: Tamula
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Wolters
authors.forename: Claire
authors.initials: C
authors.lastname: Walsek
authors.forename: Steven
authors.initials: S
authors.lastname: Zeichner
authors.forename: Lucy
authors.initials: L
authors.lastname: Civitello
mesh_terms: D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000503:physiopathology / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D012189:Retrospective Studies