Increased glucose metabolic activity is associated with CD4+ T-cell activation and depletion during chronic HIV infection

AIDS. 2014 Jan 28;28(3):297-309. doi: 10.1097/QAD.0000000000000128.


Objectives: Glucose metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and metabolism in primary CD4 and CD8 T cells.

Design and methods: Thirty-eight HIV-infected treatment-naive, 35 HIV+/combination antiretroviral therapy, seven HIV+ long-term nonprogressors and 25 HIV control individuals were studied. Basal markers of glycolysis [e.g. glucose transporter-1 (Glut1) expression, glucose uptake, intracellular glucose-6-phosphate, and L-lactate] were measured in T cells. The cellular markers of immune activation, CD38 and HLA-DR, were measured by flow cytometry.

Results: The surface expression of the Glut1 is up-regulated in CD4 T cells in HIV-infected patients compared with uninfected controls. The percentage of circulating CD4Glut1 T cells was significantly increased in HIV-infected patients and was not restored to normal levels following combination antiretroviral therapy. Basal markers of glycolysis were significantly higher in CD4Glut1 T cells compared to CD4Glut1 T cells. The proportion of CD4Glut1 T cells correlated positively with the expression of the cellular activation marker, HLA-DR, on total CD4 T cells, but inversely with the absolute CD4 T-cell count irrespective of HIV treatment status.

Conclusion: Our data suggest that Glut1 is a potentially novel and functional marker of CD4 T-cell activation during HIV infection. In addition, Glut1 expression on CD4 T cells may be exploited as a prognostic marker for CD4 T-cell loss during HIV disease progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Chronic Disease
  • Female
  • Flow Cytometry
  • Glucose / metabolism*
  • Glucose Transporter Type 1 / analysis
  • HIV Infections / immunology*
  • Humans
  • Lymphocyte Activation*
  • Male
  • Young Adult


  • Biomarkers
  • Glucose Transporter Type 1
  • SLC2A1 protein, human
  • Glucose