title: White matter microstructure among youth with perinatally acquired HIV is associated with disease severity.
abstract: OBJECTIVE
  We investigated whether HIV disease severity was associated with alterations in structural brain connectivity, and whether those alterations in turn were associated with cognitive deficits in youth with perinatally acquired HIV (PHIV).
  
  
  METHODS
  PHIV youth (n = 40) from the Pediatric HIV/AIDS Cohort Study (PHACS) (mean age: 16 ± 2 years) were included to evaluate how current and past disease severity measures (recent/nadir CD4%; peak viral load) relate to white matter microstructure within PHIV youth. PHIV youth were compared with 314 controls from the Pediatric Imaging, Neurocognition and Genetics (PING) study.
  
  
  METHODS
  Diffusion tensor imaging and tractography were utilized to assess white matter microstructure. Mediation analyses were conducted to examine whether microstructure alterations contributed to relationships between higher disease severity and specific cognitive domains in PHIV youth.
  
  
  RESULTS
  Whole brain fractional anisotropy was reduced, but radial and mean diffusivity were increased in PHIV compared with control youth. Within PHIV youth, more severe past HIV disease was associated with reduced fractional anisotropy of the right inferior fronto-occipital (IFO) and left uncinate tracts; elevated mean diffusivity of the F minor; and increased streamlines comprising the left inferior longitudinal fasciculus (ILF). Associations of higher peak viral load with lower working memory performance were partly mediated by reductions in right IFO fractional anisotropy levels.
  
  
  CONCLUSIONS
  Our findings suggest that PHIV youth have a higher risk of alterations in white matter microstructure than typically developing youth, and certain alterations are related to past disease severity. Further, white matter alterations potentially mediate associations between HIV disease and working memory.
authors.affiliation: aDepartment of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California bCenter for Biostatistics in AIDS Research, Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts cFeinberg School of Medicine, Northwestern University, Chicago, Illinois dDepartment of Neurosciences, Division of Pediatric Neurology, University of California San Diego, La Jolla eKeck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Uban
authors.forename: Megan M
authors.initials: MM
authors.lastname: Herting
authors.forename: Paige L
authors.initials: PL
authors.lastname: Williams
authors.forename: Tanvi
authors.initials: T
authors.lastname: Ajmera
authors.forename: Prapti
authors.initials: P
authors.lastname: Gautam
authors.forename: Yanling
authors.initials: Y
authors.lastname: Huo
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Malee
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.forename: John G
authors.initials: JG
authors.lastname: Csernansky
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Nichols
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Sowell
mesh_terms: D000293:Adolescent; D018791:CD4 Lymphocyte Count; D002648:Child; D003072:Cognition Disorders / Q000453:epidemiology; D056324:Diffusion Tensor Imaging; D005260:Female; D015658:HIV Infections / Q000473:pathology*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011859:Radiography; D012720:Severity of Illness Index; D019562:Viral Load; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D055815:Young Adult