Abstract
BackgroundAlthough HIV causes immune deficiency by infection and depletion of immunocytes, metabolic alterations with clinical manifestations are also reported in HIV/AIDS patients. Here we aimed to profile metabolite changes in the plasma, urine, and saliva of HIV/AIDS patients, including those on anti-retroviral therapy (ART).MethodsMetabolic profiling of biofluids collected from treatment naïve HIV/AIDS patients and those receiving ART was done with solution-state nuclear magnetic resonance (NMR) spectroscopy followed by statistical analysis and annotation.ResultsIn Principal Component Analysis (PCA) of the NMR spectra, Principal Component 1 (PC1) alone accounted for 99.3%, 87.2% and 78.8% variations in plasma, urine, and saliva, respectively. Partial least squares discriminant analysis (PLS-DA) was applied to generate three-component models, which showed plasma and urine to be better than saliva in discriminating between patients and healthy controls, and between ART-naïve patients and those receiving therapy. Twenty-six metabolites were differentially altered in any or two types of samples. Our results suggest that urinary Neopterin, and plasma Choline and Sarcosine could be used as metabolic biomarkers of HIV/AIDS infection. Pathway analysis revealed significant alternations in 12 metabolic pathways.ConclusionsThis study catalogs differentially regulated metabolites in biofluids, which helped classify subjects as healthy controls, HIV/AIDS patients, and those on ART. It also underscores the importance of further studying the consequences of HIV infection on host metabolism and its implications for pathogenesis.
Highlights
The human immunodeficiency virus (HIV) primarily infects CD4+ cells, especially T cells and monocytes
Principal Component Analysis (PCA) was performed with the first three principal components (PCs) on the plasma, urine and saliva data sets to distinguish between patients and controls on the basis of their nuclear magnetic resonance (NMR) spectra
Each sample was first classified into one of three groups – HIV/ AIDS patients who were anti-retroviral therapy (ART) naıve, patients on ART and healthy controls; this was provided as a Y-table for the Partial Least Squares Discrimination Assay (PLS-DA) analysis
Summary
The human immunodeficiency virus (HIV) primarily infects CD4+ cells, especially T cells and monocytes. Though these cells have no major role in host metabolism, clinical features of endstage HIV/AIDS patients show gross metabolic changes, manifested as weight loss and malnutrition [1], the main reasons for which are malabsorption, increased energy expenditure and metabolic alterations [2]. Several factors including HIV itself, opportunistic infections (OIs), the host immune response and ART modulate metabolic changes either directly or indirectly [4]. HIV causes immune deficiency by infection and depletion of immunocytes, metabolic alterations with clinical manifestations are reported in HIV/AIDS patients. We aimed to profile metabolite changes in the plasma, urine, and saliva of HIV/AIDS patients, including those on anti-retroviral therapy (ART)
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