title: Cerebral white matter integrity during primary HIV infection.
abstract: Inflammation and infection within the central nervous system is initiated during primary HIV infection (PHI), but the association of these processes with the integrity of brain white matter during PHI is unknown.
  
  
  
  We used diffusion tensor imaging (DTI) in this prospective cross-sectional neuroimaging study to determine the extent of white matter involvement in early HIV infection.
  
  
  
  Antiretroviral-naive PHI (defined as <1 year after infection, n = 62), chronic HIV infection (CHI, n = 16), and HIV-uninfected (n = 19) participants had DTI, laboratory, and neuropsychometric performance assessments. DTI metrics were examined using region of interest and whole brain voxelwise analyses. Linear mixed-effects models assessed correlations between DTI measures and laboratory and neuropsychometric performance values.
  
  
  
  PHI participants were assessed at a median 4.1 months after estimated infection, and had median CD4 cell count of 573 cells/μl, and HIV-1 RNA viral load of 4.5 log10 copies/ml in plasma and 2.6 log10 copies/ml in cerebrospinal fluid (CSF). DTI metrics in PHI individuals were similar to HIV- participants and correlated with disruptions in the blood-brain barrier (indicated by CSF/plasma albumin ratio and CSF protein). CHI participants had significant loss of white matter integrity that correlated with biomarkers of infection and inflammation (blood viral load, CD4 T-cell count, and neopterin, and CSF white blood cell). Within the PHI group, DTI metrics inversely correlated with increasing days since infection.
  
  
  
  In individuals assessed during PHI, group DTI measures suggested relative preservation of white matter microstructural integrity, but were associated with disruption of the blood-brain barrier and estimated duration of infection.
authors.affiliation: aDepartment of Biomedical Engineering bDepartment of Neurology, School of Medicine, St. Louis, Missouri cDepartment of Family and Preventive Medicine, UCSD, San Diego, California, USA dDepartment of Biology, University of Puerto Rico, Río Piedras, San Juan, Puerto Rico eDepartment of Psychiatry, WUSTL School of Medicine, St. Louis, Missouri fDepartment of Neurology, UCSF, San Francisco, California, USA gDivision of Biological Chemistry, Innsbruck Medical University, Innsbruck, Austria hDepartment of Radiology, WUSTL School of Medicine, St. Louis, Missouri iDepartment of Neurology, UNC, Chapel Hill, North Carolina jCenter for Imaging of Neurodegenerative Diseases, VA Medical Center, San Francisco kDepartment of Radiology and Biomedical Imaging, UCSF, San Francisco, California lDepartment of Neurology, Yale University, New Haven, Connecticut, USA. *Drs Serena S. Spudich and Beau M. Ances contributed equally to the writing of this article.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Wright
authors.forename: Florin F
authors.initials: FF
authors.lastname: Vaida
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Fernández-de Thomas
authors.forename: Jerrel
authors.initials: J
authors.lastname: Rutlin
authors.forename: Richard W
authors.initials: RW
authors.lastname: Price
authors.forename: Evelyn
authors.initials: E
authors.lastname: Lee
authors.forename: Julia
authors.initials: J
authors.lastname: Peterson
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Shimony
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Robertson
authors.forename: Rudolph
authors.initials: R
authors.lastname: Walter
authors.forename: Dieter J
authors.initials: DJ
authors.lastname: Meyerhoff
authors.forename: Serena
authors.initials: S
authors.lastname: Spudich
authors.forename: Beau M
authors.initials: BM
authors.lastname: Ances
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D001812:Blood-Brain Barrier; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes; D002490:Central Nervous System / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D003337:Corpus Callosum; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000503:physiopathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D008297:Male; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012367:RNA, Viral; D019562:Viral Load; D066127:White Matter / Q000276:immunology / Q000503:physiopathology* / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D012367:RNA, Viral