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

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 andDgroups were comparable by demographics, CD4 status, andWHOstage. Subtype A infections had higher log viral loads (median 5.0 vs. 4.6, P¼0.02). Children with A performed more poorly than those with D on all measures, especially on KABC-2 Sequential Processing (memory) (P¼0.01), Simultaneous Processing (visual–spatial analysis) (P¼0.005), Learning (P¼0.02), and TOVA visual attention (P¼0.04). 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.