Date Published:
2015 Oct

Publication Type:
Journal Article

Authors:

A.M. Anderson
C. Fennema-Notestine
A. Umlauf
M.J. Taylor
D.B. Clifford
C.M. Marra
A.C. Collier
B.B. Gelman
J.C. McArthur
A. McCutchan
D.M. Simpson
S. Morgello
I. Grant
S.L. Letendre

Secondary:
J Neurovirol

Volume:
21

Pagination:
559-67

Issue:
5

PMID:
26069183

URL:
https://pubmed.ncbi.nlm.nih.gov/26069183

DOI:
10.1007/s13365-015-0359-6

Keywords:
Adult;AIDS Dementia Complex;Biomarkers;Brain;CHARTER;Chemotaxis, Leukocyte;Cohort Studies;Cross-Sectional Studies;Female;Humans;Internal;Magnetic Resonance Spectroscopy;Male;Middle Aged;Monocytes

Abstract:
<p>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.</p>