Nuclear magnetic resonance based profiling of biofluids reveals metabolic dysregulation in HIV-infected persons and those on anti-retroviral therapy

PLoS One. 2013 May 16;8(5):e64298. doi: 10.1371/journal.pone.0064298. Print 2013.

Abstract

Background: Although 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).

Methods: Metabolic 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.

Results: In 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.

Conclusions: This 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism*
  • Humans
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Metabolome / physiology*
  • Metabolomics / methods*
  • Middle Aged
  • Principal Component Analysis
  • Young Adult

Substances

  • Anti-Retroviral Agents

Grants and funding

The authors thank Department of Biotechnology (DBT), Government of India for providing financial support for the 500 MHz and 700 MHz NMR spectrometers at the ICGEB and NII, New Delhi. SUM received a Pre-Doctoral Fellowship from ICGEB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.