title: Plasma and Cerebrospinal Fluid Biomarkers Predict Cerebral Injury in HIV-Infected Individuals on Stable Combination Antiretroviral Therapy.
abstract: OBJECTIVE
  HIV-associated brain injury persists despite combination antiretroviral therapy, but contributing factors remain poorly understood. We postulated that inflammation-associated biomarkers will be associated with cerebral injury on proton magnetic resonance spectroscopy in chronically HIV-infected subjects.
  
  
  METHODS
  Five biomarkers were measured in 197 HIV-infected subjects: soluble CD14, MCP-1, IP-10, MIP-1β, and fractalkine. Levels of N-acetyl aspartate (NAA), Choline (Cho), Myoinositol (MI), Glutamate + Glutamine (Glx), and Creatine (Cr) were acquired in the midfrontal cortex (MFC), frontal white matter, and basal ganglia (BG). Predictive models were built through linear regression, and the best models were chosen using the Akaike Information Criterion.
  
  
  RESULTS
  Increases in plasma or CSF MCP-1 were associated with lower NAA/Cr in the MFC and BG, whereas metabolite changes in the frontal white matter for NAA/Cr, GlxCr, and Cho/Cr were explained almost exclusively by a single factor, sCD14. Plasma and CSF levels of this factor were also significantly associated with Glx/Cr in MFC and BG. Higher CSF FKN was associated with higher NAA/Cr in BG. Best predictors for higher Cho/Cr in BG and MFC were CSF sCD14 and CSF MIP-1β. Plasma and CSF IP-10 were only associated with Cho/Cr in MFC. Of the 3 models that simultaneously accounted for both plasma and CSF, there were more associations between CSF biomarkers and magnetic resonance spectroscopy metabolites.
  
  
  CONCLUSIONS
  Markers of inflammation and immune activation, in particular MCP-1 and sCD14, predominantly reflecting CNS sources, contribute to the persistence of brain injury in a metabolite and region-dependent manner in chronically HIV-infected patients on stable combination antiretroviral therapy.
authors.affiliation: *Emory University, Atlanta, GA; †Indiana University, Indianapolis, IN; ‡University of California, San Diego, San Diego, CA; §University of California, Los Angeles, CA; ‖University of Rochester School of Medicine, Rochester, NY; ¶University of Colorado Medical Center, Denver, CO; #University of Pittsburgh, Pittsburgh, PA; **University of Hawaii, Honolulu, HI; ††University of Florida, Gainesville, FL; and ‡‡Tufts University School of Medicine, Boston, MA.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Anderson
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Harezlak
authors.forename: Ajay
authors.initials: A
authors.lastname: Bharti
authors.forename: Deming
authors.initials: D
authors.lastname: Mi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Taylor
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Giovanni
authors.initials: G
authors.lastname: Schifitto
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhong
authors.forename: Jeffry R
authors.initials: JR
authors.lastname: Alger
authors.forename: Mark S
authors.initials: MS
authors.lastname: Brown
authors.forename: Elyse J
authors.initials: EJ
authors.lastname: Singer
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Campbell
authors.forename: Deborah D
authors.initials: DD
authors.lastname: McMahon
authors.forename: Steven
authors.initials: S
authors.lastname: Buchthal
authors.forename: Ronald
authors.initials: R
authors.lastname: Cohen
authors.forename: Constantin
authors.initials: C
authors.lastname: Yiannoutsos
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
authors.forename: Bradford A
authors.initials: BA
authors.lastname: Navia
mesh_terms: D015526:AIDS Dementia Complex / Q000473:pathology*; D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000032:analysis* / Q000097:blood*; D001921:Brain / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry*
chemical_list: D044966:Anti-Retroviral Agents; D015415:Biomarkers