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Open Access Research

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

Lillian Seu12, Gabriel M Ortiz13, Trevor D Burt45, Steven G Deeks6, Jeffrey N Martin67 and Joseph M McCune1*

Author Affiliations

1 Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA

2 Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94110, USA

3 Division of Hospital Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA

4 Division of Neonatology, Department of Pediatrics, University of California, San Francisco, CA 94110, USA

5 Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94110, USA

6 Positive Health Program, Department of Medicine, University of California, San Francisco, CA 94110, USA

7 Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94110, USA

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AIDS Research and Therapy 2014, 11:27  doi:10.1186/1742-6405-11-27

Published: 5 August 2014

Abstract

The level (or frequency) of circulating monocyte subpopulations such as classical (CD14hiCD16-) and non-classical (CD14dimCD16+) 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 (CD14hiCD16-) and decreased levels of non-classical monocyte populations (CD14dimCD16+). 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.

Keywords:
HIV; HO-1; Immune activation; Monocytes; CD4+ T cell recovery