title: 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: 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.
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA ; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94110, USA.
authors.forename: Lillian
authors.initials: L
authors.lastname: Seu
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA ; Division of Hospital Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA.
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Ortiz
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of California, San Francisco, CA 94110, USA ; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94110, USA.
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Burt
authors.affiliation: Positive Health Program, Department of Medicine, University of California, San Francisco, CA 94110, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: Positive Health Program, Department of Medicine, University of California, San Francisco, CA 94110, USA ; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94110, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
keywords: CD4+ T cell recovery; HIV; HO-1; Immune activation; Monocytes