HIV-subtype A is associated with poorer neuropsychological performance compared with subtype D in antiretroviral therapy-naive Ugandan children
International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, MI, United States; Division of Infectious Disease, Department of Pediatrics, University of California, San Francisco, San Francisco, CA, United States; Department of Pediatrics, University of Washington Seattle Children's Hospital, Seattle, WA, United States; Department of Psychiatry, Makerere University School of Medicine, Kampala, Uganda; California Department of Public Health, Viral and Rickettsial Disease Laboratory, Richmond, CA, United States; Makerere University-Walter Reed Program, Kampala, Uganda; Department of Medicine, University of California, San Francisco, San Francisco, United States; Department of Medicine, University of California, San Francisco, San Francisco General Hospital, San Francisco, CA, United States; Department of Medicine, Makerere University School of Medicine, Kampala, Uganda; Department of Paediatrics and Child Health, Makerere University School of Medicine, Kampala, Uganda; Section of Infectious Diseases, Department of Medicine, University of California, San Francisco, San Francisco, CA, United States
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. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
antiretrovirus agent; Gag protein; glycoprotein gp 41; Pol protein; virus envelope protein; Vpu protein; article; Bruininks Oseretsky Test for Motor Proficiency; CD4 lymphocyte count; child; comparative study; controlled study; depth perception; disease association; female; human; Human immunodeficiency virus; Human immunodeficiency virus infection; kaufman assessment battery for children; learning; major clinical study; male; neuropsychological test; polymerase chain reaction; preschool child; priority journal; school child; Test of Variables of Attention; Uganda; virus load; vision; AIDS Dementia Complex; Antiretroviral Therapy, Highly Active; Child; Disease Progression; Female; Genetic Variation; HIV Infections; HIV-1; Humans; Male; Neuropsychological Tests; RNA, Viral; Uganda; Viral Tropism