title: Early Antiretroviral Therapy in HIV-Infected Children Is Associated with Diffuse White Matter Structural Abnormality and Corpus Callosum Sparing.
abstract: Fractional anisotropy in the frontal white matter, corpus callosum, and internal capsule is abnormal in human immunodeficiency virus-positive (HIV+) adults. We describe the distribution and nature of white matter abnormalities in a cohort of children who started antiretroviral therapy within the first year of life and the benefit of early treatment by using DTI measures (fractional anisotropy and mean, axial, and radial diffusion).
  
  
  
  DTI was performed on children in a neurodevelopmental substudy from the Children with HIV Early Antiretroviral trial. Voxel-based group comparisons were obtained to determine regions where fractional anisotropy and mean diffusion differed between HIV+ and uninfected children. Associations of DTI parameters with the timing of antiretroviral therapy initiation were examined.
  
  
  
  Thirty-nine HIV+ children (15 boys; mean age, 5.4 years) and 13 controls (5 boys; mean age, 5.7 years) were scanned. Two clusters with lower fractional anisotropy and 7 clusters with increased mean diffusion were identified in the HIV+ group, with symmetric distribution predominantly due to increased radial diffusion, suggestive of decreased myelination. Corticospinal tracts rather than the corpus callosum were predominantly involved. Children on early-interrupted antiretroviral therapy had lower fractional anisotropy compared with those receiving continuous treatment.
  
  
  
  HIV+ children at 5 years of age have white matter abnormalities measured by fractional anisotropy, despite early antiretroviral therapy, suggesting that early antiretroviral therapy does not fully protect the white matter from either peripartum or in utero infection. In contrast to adults, the corticospinal tracts are predominantly involved rather than the corpus callosum, possibly due to early antiretroviral therapy. Continuous early antiretroviral therapy can limit white matter damage.
authors.affiliation: From the Departments of Radiodiagnosis (C.A.) ca@sun.ac.za.
authors.forename: C
authors.identifier: 0000-0002-4598-1127
authors.initials: C
authors.lastname: Ackermann
authors.affiliation: Clinical Research and Imaging Centre, Bristol (S.A.), University of Bristol, Bristol, UK.|Department of Paediatric Radiology (S.A.), Bristol Royal Hospital for Children, Bristol, UK.
authors.forename: S
authors.identifier: 0000-0002-1015-9790
authors.initials: S
authors.lastname: Andronikou
authors.affiliation: Department of Human Biology (M.G.S., A.A.A., E.M.M.), Medical Research Council/University of Cape Town Medical Imaging Research Unit, University of Cape Town, Cape Town, South Africa.
authors.forename: M G
authors.identifier: 0000-0001-6921-112X
authors.initials: MG
authors.lastname: Saleh
authors.affiliation: Paediatrics and Child Health (B.L., M.F.C.), Faculty of Medicine and Health Sciences.
authors.forename: B
authors.identifier: 0000-0001-7260-7723
authors.initials: B
authors.lastname: Laughton
authors.affiliation: Department of Human Biology (M.G.S., A.A.A., E.M.M.), Medical Research Council/University of Cape Town Medical Imaging Research Unit, University of Cape Town, Cape Town, South Africa.
authors.forename: A A
authors.identifier: 0000-0003-0188-0591
authors.initials: AA
authors.lastname: Alhamud
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging (A.v.d.K.), Massachusetts General Hospital, Charlestown, Massachusetts.
authors.forename: A
authors.identifier: 0000-0002-2754-6594
authors.initials: A
authors.lastname: van der Kouwe
authors.affiliation: Centre for Statistical Consultation (M.K.), Stellenbosch University, Tygerberg, South Africa.
authors.forename: M
authors.identifier: 0000-0002-4887-7296
authors.initials: M
authors.lastname: Kidd
authors.affiliation: Paediatrics and Child Health (B.L., M.F.C.), Faculty of Medicine and Health Sciences.
authors.forename: M F
authors.identifier: 0000-0003-2559-6034
authors.initials: MF
authors.lastname: Cotton
authors.affiliation: Department of Human Biology (M.G.S., A.A.A., E.M.M.), Medical Research Council/University of Cape Town Medical Imaging Research Unit, University of Cape Town, Cape Town, South Africa.
authors.forename: E M
authors.identifier: 0000-0002-0781-3632
authors.initials: EM
authors.lastname: Meintjes
mesh_terms: D000293:Adolescent; D000328:Adult; D016880:Anisotropy; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003337:Corpus Callosum / Q000000981:diagnostic imaging / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011712:Pyramidal Tracts / Q000000981:diagnostic imaging / Q000473:pathology*; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology*
chemical_list: D019380:Anti-HIV Agents