title: A combined chemometric and quantitative NMR analysis of HIV/AIDS serum discloses metabolic alterations associated with disease status.
abstract: Individuals infected with the human immunodeficiency virus (HIV) often suffer from concomitant metabolic complications. Treatment with antiretroviral therapy has also been shown to alter the metabolism of patients. Although chemometric analysis of nuclear magnetic resonance (NMR) spectra of human sera can distinguish normal sera (HIVneg) from HIV-infected sera (HIVpos) and sera from HIV-infected patients on antiretroviral therapy (ART), quantitative analysis of the discriminating metabolites and their relationship to disease status has yet to be determined. The objectives of the study were to analyze NMR spectra of HIVneg, HIVpos, and ART serum samples with a combination of chemometric and quantitative methods and to compare the NMR data with disease status as measured by viral load and CD4 count. High-resolution magic angle spinning (HRMAS) NMR spectroscopy was performed on HIVneg (N = 10), HIVpos (N = 10), and ART (N = 10) serum samples. Chemometric linear discriminant analysis classified the three groups of spectra with 100% accuracy. Concentrations of 12 metabolites were determined with a semi-parametric metabolite quantification method named high-resolution quantum estimation (HR-QUEST). CD4 count was directly associated with alanine (p = 0.008), and inversely correlated with both glutamine (p = 0.017) and glucose (p = 0.022) concentrations. A multivariate linear model using alanine, glutamine and glucose as covariates demonstrated an association with CD4 count (p = 0.038). The combined chemometric and quantitative analysis of the data disclosed previously unknown associations between specific metabolites and disease status. The observed associations with CD4 count are consistent with metabolic disorders that are commonly seen in HIV-infected patients.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
authors.forename: Tracy R
authors.initials: TR
authors.lastname: McKnight
authors.forename: Hikari A I
authors.initials: HA
authors.lastname: Yoshihara
authors.forename: Lungile J
authors.initials: LJ
authors.lastname: Sitole
authors.forename: Jeffery N
authors.initials: JN
authors.lastname: Martin
authors.forename: Francois
authors.initials: F
authors.lastname: Steffens
authors.forename: Debra
authors.initials: D
authors.lastname: Meyer
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000188:drug therapy / Q000821:virology; D000409:Alanine / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D018791:CD4 Lymphocyte Count; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000097:blood; D006679:HIV Seropositivity / Q000097:blood* / Q000821:virology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D019562:Viral Load
chemical_list: D015415:Biomarkers; D005973:Glutamine; D005947:Glucose; D000409:Alanine
references.citation: Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E278-84
references.pmid: 15367396
references.citation: AIDS. 2003 May 23;17(8):1179-93
references.pmid: 12819520
references.citation: J Nutr Biochem. 1999 Jun;10(6):316-24
references.pmid: 15539305
references.citation: J Clin Lipidol. 2009 Dec 1;3(6):379-384
references.pmid: 20161509
references.citation: J Pharm Biomed Anal. 2006 Jun 16;41(4):1442-6
references.pmid: 16621406
references.citation: Int Immunol. 1989;1(4):367-72
references.pmid: 2577375
references.citation: Q J Exp Physiol. 1985 Oct;70(4):473-89
references.pmid: 3909197
references.citation: Clin Chem. 1994 May;40(5):785-9
references.pmid: 7909726
references.citation: J Biomol NMR. 2009 Jul;44(3):127-37
references.pmid: 19513588
references.citation: J Acquir Immune Defic Syndr. 2008 Jul 1;48(3):281-8
references.pmid: 18545156
references.citation: J Proteome Res. 2009 Jan;8(1):352-61
references.pmid: 19063642
references.citation: J Clin Med Res. 2010 Mar 20;2(2):55-61
references.pmid: 21811520
references.citation: NMR Biomed. 2000 May;13(3):129-53
references.pmid: 10861994
references.citation: Br J Nutr. 2007 Aug;98(2):237-52
references.pmid: 17403271
references.citation: PLoS One. 2013 May 16;8(5):e64298
references.pmid: 23696880
references.citation: World J Gastroenterol. 2012 Aug 7;18(29):3775-81
references.pmid: 22876026
references.citation: OMICS. 2013 Jan;17(1):5-15
references.pmid: 21751871
references.citation: Magn Reson Med. 2009 Mar;61(3):525-32
references.pmid: 19235261
references.citation: Annu Rev Med. 2004;55:303-17
references.pmid: 14746523
references.citation: Am J Physiol Cell Physiol. 2006 Oct;291(4):C618-26
references.pmid: 16687472
references.citation: NMR Biomed. 2010 Dec;23(10):1146-57
references.pmid: 20842756
references.citation: Am J Cardiol. 2008 Apr 15;101(8):1213-7
references.pmid: 18394461
references.citation: Magn Reson Med. 2004 Apr;51(4):649-54
references.pmid: 15065235
references.citation: Antiviral Res. 2001 Sep;51(3):151-77
references.pmid: 11448728
references.citation: Lung Cancer. 2010 Apr;68(1):44-50
references.pmid: 19559498
references.citation: J Magn Reson Imaging. 2011 Apr;33(4):808-16
references.pmid: 21448944
references.citation: Trends Pharmacol Sci. 2005 Feb;26(2):88-93
references.pmid: 15681026
references.citation: Am J Physiol. 1998 Oct;275(4):E577-83
references.pmid: 9755075
references.citation: AIDS. 1997 Feb;11(2):147-55
references.pmid: 9030360
references.citation: J Proteome Res. 2010 Jan;9(1):319-32
references.pmid: 19908917
references.citation: J Biol Chem. 1976 Feb 10;251(3):826-35
references.pmid: 1249058
references.citation: Mol Biosyst. 2013 Jan 27;9(1):18-28
references.pmid: 23114495
references.citation: AIDS Res. 1984-1985;1(6):423-38
references.pmid: 6085927
references.citation: J Oncol. 2011;2011:174019
references.pmid: 21577256