CSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease

• Type of Material: Article
• Authors: Albert Anderson, Emory University; Christine Fennema-Notestine, University of California San Diego; Anya Umlauf, University of California San Diego; Michael J. Taylor, University of California San Diego; David B. Clifford, Washington University; Christina M. Marra, University of Washington; Ann C. Collier, University of Washington; Benjamin B. Gelman, University of Texas Medical Branch; Justin C. McArthur, Johns Hopkins University; J. Allen McCutchan, University of California San Diego; David M. Simpson, Mount Sinai Hospital; Susan Morgello, Mount Sinai Hospital; Igor Grant, University of California San Diego; Scott L. Letendre, University of California San Diego; CHARTER Group
• Language: English
• Date: 2015-10-01
• Publisher: Taylor & Francis
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015, Journal of NeuroVirology, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1007/s13365-015-0359-6
• Title of Journal or Parent Work: Journal of NeuroVirology
• ISSN: 1355-0284
• Volume: 21
• Issue: 5
• Start Page: 559
• End Page: 567
• Grant/Funding Information: AMA is supported by NIH K23 MH095679 and SLL is supported by K24 MH097673.; This work was supported by awards from the National Institutes of Health for the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) [N01 MH2205 and HHSN271201000036C] and P30 MH62512.
• Keywords: Virology; INFECTION; CHEMOKINES; HIV-associated neurocognitive disorder; INDIVIDUALS; HIV/AIDS; IMMUNE ACTIVATION; Neurosciences; Cerebrospinal fluid; IMPAIRMENT; BRAIN; Neurosciences & Neurology; CEREBROSPINAL-FLUID; Human immunodeficiency virus; Biomarkers; NEUROCOGNITIVE DISORDERS; INFLAMMATION; Life Sciences & Biomedicine; Acquired immunodeficiency syndrome; Science & Technology
• Research Categories: Health Sciences, Epidemiology; Biology, Virology; Biology, Neuroscience

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 (R2 0.179, p < 0.001) as well as MCP-1 and MI in FWM (R2 0.137, p = 0.002). Higher Cr levels in FWM were associated with MCP-1 (R2 0. 075, p = 0.01) and IP-10 (R2 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 (R2 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.