HIV-subtype A is associated with poorer neuropsychological

Paediatric treatment

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

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. One hundred and two HIV-infected antiretroviral therapy 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. 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. 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 antiretroviral therapy and the selection of drugs with greater central nervous system penetration.

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Editors’ note: The findings of this study implicating subtype A in poorer neurocognitive performance in children are somewhat surprising, given that subtype D is most commonly associated with dementia in adults in Uganda. Given that the children were at an earlier stage of disease, the difference may be in viral tropism, the cell type that HIV infects and replicates in. CCR5 viruses, the predominant form in early infection, infect macrophages, which are the principal cells that transport the virus through the blood-brain barrier, and microglia, which are the other major target cell for HIV in the central nervous system. This may explain the effects reported here during the sensitive period of brain development in children. Further studies are needed to confirm these findings and describe the neurodevelopmental trajectory of children with HIV infection by subtype but they do suggest that consideration of subtype will be important in determining which children should be started early on antiretroviral treatment. In any case, WHO recommends that ART should be started for all HIV-infected infants diagnosed in the first year of life, irrespective of CD4 count or WHO clinical stage.