title: Plasma sCD14 is a biomarker associated with impaired neurocognitive test performance in attention and learning domains in HIV infection.
abstract: OBJECTIVE
  Mild forms of HIV-associated neurocognitive disorders (HAND) remain prevalent in the era of combination antiretroviral therapy (cART). Although elevated lipopolysaccharide (LPS) and immune activation are implicated in HAND pathogenesis, relationships of LPS and inflammatory markers to mild forms of HAND or impairment in specific cognitive domains are unknown. To examine these relationships, we compared plasma soluble CD14 (sCD14), CCL2, and LPS levels with neurocognitive test scores in a cART era cohort.
  
  
  METHODS
  We analyzed plasma from HIV+ subjects (n = 97) with nadir CD4 counts <300 and high frequency of hepatitis C virus coinfection and illicit drug use for relationships between sCD14, CCL2, and LPS levels and neurocognitive test scores.
  
  
  RESULTS
  Plasma sCD14 levels were higher in subjects with test scores indicating global impairment (P = 0.007), particularly in attention and learning domains (P = 0.015 and P = 0.03, respectively), regardless of HAND diagnosis. Plasma sCD14 levels correlated inversely with global, attention, and learning T scores (P = 0.036, 0.047, and 0.007, respectively) and yielded higher area under receiver operating characteristic values for predicting impaired scores than single-marker models based on plasma or cerebrospinal fluid viral load or CD4 count (area under receiver operating characteristic values = 0.71, 0.81, and 0.71, respectively) and in 4-marker models based on plasma sCD14 and 3 conventional markers compared with the 3-marker models.
  
  
  CONCLUSIONS
  Plasma sCD14 is a biomarker associated with impaired neurocognitive testing in attention and learning domains in HIV-infected individuals with advanced disease, suggesting involvement of cortical and limbic pathways by inflammatory processes in the cART era. Plasma sCD14 is a potential biomarker to monitor HAND progression and therapeutic responses.
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Lyons
authors.forename: Hajime
authors.initials: H
authors.lastname: Uno
authors.forename: Petronela
authors.initials: P
authors.lastname: Ancuta
authors.forename: Anupa
authors.initials: A
authors.lastname: Kamat
authors.forename: David J
authors.initials: DJ
authors.lastname: Moore
authors.forename: Elyse J
authors.initials: EJ
authors.lastname: Singer
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.forename: Dana
authors.initials: D
authors.lastname: Gabuzda
mesh_terms: D015526:AIDS Dementia Complex / Q000097:blood / Q000503:physiopathology / Q000523:psychology*; D000328:Adult; D000368:Aged; D001288:Attention; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D006526:Hepatitis C / Q000097:blood / Q000150:complications; D006801:Humans; D007858:Learning; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009293:Opioid-Related Disorders / Q000150:complications; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides