Levels of circulating myeloid subpopulations and of heme oxygenase-1 do not predict CD4+ T cell recovery after the initiation of antiretroviral therapy for HIV disease

Abstract

Doc number: 27

Abstract: The level (or frequency) of circulating monocyte subpopulations such as classical (CD14^hi CD16^- ) and non-classical (CD14^dim CD16⁺ ) monocytes varies during the course of HIV disease progression and antiretroviral therapy (ART). We hypothesized that such variation and/or differences in the degree to which these cells expressed the immunoregulatory enzyme, heme oxygenase-1 (HO-1), would be associated with CD4⁺ T cell recovery after the initiation of ART. This hypothesis was tested in a cross-sectional study of four groups of HIV-infected subjects, including those who were seronegative, untreated virologic controllers [detectable viral load (VL) of <1000 copies/mL], untreated virologic non-controllers [VL > 10,000 copies/mL], and ART-mediated virologic controllers [VL < 75 copies/mL]. A longitudinal analysis of ART-treated subjects was also performed along with regression analysis to determine which biomarkers were associated with and/or predictive of CD4⁺ T cell recovery. Suppressive ART was associated with increased levels of classical monocyte subpopulations (CD14^hi CD16^- ) and decreased levels of non-classical monocyte populations (CD14^dim CD16⁺ ). Among peripheral blood mononuclear cells (PBMCs), HO-1 was found to be most highly up-regulated in CD14⁺ monocytes after ex vivo stimulation. Neither the levels of monocyte subpopulations nor of HO-1 expression in CD14⁺ monocytes were significantly associated with the degree of CD4⁺ T cell recovery. Monocyte subpopulations and HO-1 gene expression were, however, restored to normal levels by suppressive ART. These results suggest that the level of circulating monocyte subpopulations and their expression of HO-1 have no evident relationship to CD4⁺ T cell recovery after the initiation of ART.