title: CSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease.
abstract: Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) persist despite combination antiretroviral therapy (cART), supporting the need to better understand HIV neuropathogenesis. Magnetic resonance spectroscopy (MRS) of the brain has demonstrated abnormalities in HIV-infected individuals despite cART. We examined the associations between MRS metabolites and selected cerebrospinal fluid (CSF) biomarkers reflecting monocyte/macrophage activation and chemotaxis. A multicenter cross-sectional study involving five sites in the USA was conducted. The following CSF biomarkers were measured: soluble CD14 (sCD14), monocyte chemotactic protein-1 (MCP-1), interferon inducible protein 10 (IP-10), and stromal cell-derived growth factor 1 alpha (SDF-1α). The following MRS metabolites were measured from basal ganglia (BG), frontal white matter (FWM), and frontal gray matter (FGM): N-acetylaspartate (NAA), myo-inositol (MI), choline (Cho), and creatine (Cr). CSF biomarkers were compared to absolute MRS metabolites as well as metabolite/Cr ratios using linear regression. Eighty-three HIV-infected individuals were included, 78 % on cART and 37 % with HAND. The most robust positive correlations were between MCP-1 and Cho in BG (R (2) 0.179, p < 0.001) as well as MCP-1 and MI in FWM (R (2) 0.137, p = 0.002). Higher Cr levels in FWM were associated with MCP-1 (R (2) 0. 075, p = 0.01) and IP-10 (R (2) 0.106, p = 0.003). Comparing biomarkers to MRS metabolite/Cr ratios impacted some relationships, e.g., higher sCD14 levels were associated with lower Cho/Cr ratios in FGM (R (2) 0.224, p < 0.001), although higher MCP-1 levels remained associated with Cho/Cr in BG. These findings provide evidence that monocyte activation and chemotaxis continue to contribute to HIV-associated brain abnormalities in cART-treated individuals.
authors.affiliation: Emory School of Medicine, Emory University, Atlanta, GA, USA.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Anderson
authors.affiliation: University of California, San Diego, La Jolla, CA, USA.|HIV Neurobehavioral Research Center and Antiviral Research Center, University of California, San Diego, 220 Dickinson Street, Suite A, San Diego, CA, 92103, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Fennema-Notestine
authors.affiliation: University of California, San Diego, La Jolla, CA, USA.|HIV Neurobehavioral Research Center and Antiviral Research Center, University of California, San Diego, 220 Dickinson Street, Suite A, San Diego, CA, 92103, USA.
authors.forename: Anya
authors.initials: A
authors.lastname: Umlauf
authors.affiliation: University of California, San Diego, La Jolla, CA, USA.|HIV Neurobehavioral Research Center and Antiviral Research Center, University of California, San Diego, 220 Dickinson Street, Suite A, San Diego, CA, 92103, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Taylor
authors.affiliation: Washington University School of Medicine, Washington University, St. Louis, MO, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Marra
authors.affiliation: University of Washington, Seattle, WA, USA.
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.affiliation: University of Texas Medical Branch, University of Texas System, Galveston, TX, USA.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.affiliation: John Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.affiliation: University of California, San Diego, La Jolla, CA, USA.|HIV Neurobehavioral Research Center and Antiviral Research Center, University of California, San Diego, 220 Dickinson Street, Suite A, San Diego, CA, 92103, USA.
authors.forename: J Allen
authors.initials: JA
authors.lastname: McCutchan
authors.affiliation: The Mount Sinai Hospital, New York, NY, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.affiliation: The Mount Sinai Hospital, New York, NY, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.affiliation: University of California, San Diego, La Jolla, CA, USA.|HIV Neurobehavioral Research Center and Antiviral Research Center, University of California, San Diego, 220 Dickinson Street, Suite A, San Diego, CA, 92103, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.affiliation: University of California, San Diego, La Jolla, CA, USA. sletendre@ucsd.edu.|HIV Neurobehavioral Research Center and Antiviral Research Center, University of California, San Diego, 220 Dickinson Street, Suite A, San Diego, CA, 92103, USA. sletendre@ucsd.edu.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Letendre
mesh_terms: D015526:AIDS Dementia Complex / Q000378:metabolism*; D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001921:Brain / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*
chemical_list: D015415:Biomarkers
keywords: Acquired immunodeficiency syndrome; Biomarkers; Cerebrospinal fluid; HIV-associated neurocognitive disorder; Human immunodeficiency virus