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. 2010 May 15;24(8):1163-70.
doi: 10.1097/qad.0b013e3283389dcc.

HIV-subtype A is associated with poorer neuropsychological performance compared with subtype D in antiretroviral therapy-naive Ugandan children

Michael J Boivin  1 , Theodore D Ruel, Hannah E Boal, Paul Bangirana, Huyen Cao, Leigh A Eller, Edwin Charlebois, Diane V Havlir, Moses R Kamya, Jane Achan, Carolyne Akello, Joseph K Wong
Affiliations

HIV-subtype A is associated with poorer neuropsychological performance compared with subtype D in antiretroviral therapy-naive Ugandan children

Michael J Boivin et al. AIDS. .

Abstract

Background: HIV-subtype D is associated with more rapid disease progression and higher rates of dementia in Ugandan adults compared with HIV-subtype A. There are no data comparing neuropsychological function by HIV subtype in Ugandan children.

Design: One hundred and two HIV-infected antiretroviral therapy (ART) naive Ugandan children 6-12 years old (mean 8.9) completed the Kaufman Assessment Battery for Children, second edition (KABC-2), the Test of Variables of Attention (TOVA), and the Bruininks-Oseretsky Test for Motor Proficiency, second edition (BOT-2). Using a PCR-based multiregion assay with probe hybridization in five different regions (gag, pol, vpu, env, gp-41), HIV subtype was defined by hybridization in env and by total using two or more regions. Analysis of covariance was used for multivariate comparison.

Results: The env subtype was determined in 54 (37 A, 16 D, 1 C) children. Subtype A and D groups were comparable by demographics, CD4 status, and WHO stage. Subtype A infections had higher log viral loads (median 5.0 vs. 4.6, P = 0.02). Children with A performed more poorly than those with D on all measures, especially on KABC-2 Sequential Processing (memory) (P = 0.01), Simultaneous Processing (visual-spatial analysis) (P = 0.005), Learning (P = 0.02), and TOVA visual attention (P = 0.04). When adjusted for viral load, Sequential and Simultaneous Processing remained significantly different. Results were similar comparing by total HIV subtype.

Conclusion: HIV subtype A children demonstrated poorer neurocognitive performance than those with HIV subtype D. Subtype-specific neurocognitive deficits may reflect age-related differences in the neuropathogenesis of HIV. This may have important implications for when to initiate ART and the selection of drugs with greater central nervous system penetration.

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Conflict of interest statement

DISCLOSURES

None of the authors have any conflicts of interest to disclose with respect to this study. All of the authors have contributed substantially to the present study and merit inclusion as co-authors.

Michael J. Boivin designed the assessment portion of the study, completed the analyses, and wrote the paper.

Theodore D. Ruel helped organize the subtype and clinical lab tests and data management of these assessments, and contributed to the writing of the paper.

Hannah E. Boal helped supervise study recruitment, consent, neuropsychological assessment, data management, and contributed to the writing of the paper.

Paul Bangirana supervised study consent, neuropsychological assessment, data management, data analysis, formulation of tables, and contributed to the writing of the paper.

Huyen Cao directed immunophenotyping assays for T cell activation and laboratory interpretation.

Leigh Anne Eller assisted in the immunological and clinical assays for T cell activation and laboratory interpretation.

Edwin Charlebois helped with patient selection and recruitment, provided statistical and data management support and contributed to the writing of the paper.

Diane Havlir assisted in patient selection and recruitment, clinical coordination and contributed to the conceptualization of the study.

Moses Kamya contributed to study design, patient selection and recruitment, clinical coordination and contributed to the writing of the paper.

Jane Achan contributed to patient selection and recruitment and clinical coordination.

Carolyne Akello contributed to patient selection and recruitment and clinical coordination.

Joseph K Wong developed the overall design of the study, helped organize and interpret the subtype and clinical lab tests, contributed to the interpretation of the study findings, helped write the manuscript, and was PI on the NIMH R21 grant that provided the principal support for this work.

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