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

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 HLADR, were measured by flow cytometry. Results: The surface expression of the Glut1 is up-regulated in CD4⁺ T cells in HIVinfected patients compared with uninfected controls. The percentage of circulating CD4⁺Glut1⁺ 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 CD4⁺Glut1⁺ T cells compared to CD4⁺Glut1^- T cells. The proportion of CD4⁺Glut1⁺ 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.