title: White matter micro-structural changes in ART-naive and ART-treated children and adolescents infected with HIV in South Africa.
abstract: OBJECTIVE
  To describe the effect of HIV on white matter integrity and neurocognitive function in children vertically infected with HIV, compared to a HIV-negative healthy control group.
  
  
  METHODS
  Cross-sectional.
  
  
  METHODS
  We compared 75 HIV-infected children aged 6-16 years, including children on antiretroviral therapy (ART) and those who were ART-naive, with 30 controls on diffusion tensor imaging and a neuropsychological battery sensitive to fronto-striatal pathology. In a secondary analysis, we compared 'slow progressor' ART-naive children, children on ART without a diagnosis of encephalopathy and children on ART with HIV encephalopathy.
  
  
  RESULTS
  Compared to controls (n = 30), HIV-infected children (n = 75) displayed decreased fractional anisotropy and axial diffusion, and increased mean diffusivity and radial diffusion, indicating damaged neuronal microstructure. HIV-infected children performed poorly on the neuropsychological battery (P = <0.001). Within the HIV-infected group, children with HIV encephalopathy (n = 14) had poor white matter integrity when compared to ART-treated children without encephalopathy (n = 41), and there was significant myelin loss in ART-naive children (n = 20), compared with ART-treated children. ART-treated children had significant axonal damage in the corpus callosum (P = 0.009).
  
  
  CONCLUSIONS
  Children infected with HIV, irrespective of treatment status, displayed significantly poorer white matter integrity and impaired cognition compared to HIV-negative controls. Our findings suggest that despite immune recovery in children on ART, they remain at risk for developing central nervous system disease, and that initiation of ART as early as possible may reduce the risk of developing white matter damage in ART-naive slow progressors.
authors.affiliation: aDepartment of Psychiatry and Mental Health bDepartment of Pediatrics, School of Child and Adolescent Health cDepartment of Psychology, University of Cape Town, Cape Town, South Africa dDepartment of Psychology and Behavioural Neuroscience, University of Missouri, St Louis, Missouri, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Hoare
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Fouche
authors.forename: Nicole
authors.initials: N
authors.lastname: Phillips
authors.forename: John A
authors.initials: JA
authors.lastname: Joska
authors.forename: Robert
authors.initials: R
authors.lastname: Paul
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Donald
authors.forename: Kevin G F
authors.initials: KG
authors.lastname: Thomas
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Stein
mesh_terms: D015526:AIDS Dementia Complex / Q000473:pathology*; D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D002648:Child; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D013019:South Africa; D016896:Treatment Outcome; D066127:White Matter / Q000473:pathology*
chemical_list: D044966:Anti-Retroviral Agents