ABSTRACT
BACKGROUND: Soluble biomarkers of inflammation predict non-AIDS related morbidity and mortality among human immunodeficiency virus (HIV)-infected persons. Exploring associations between plasma biomarkers and cellular phenotypes may identify sources of excess inflammation. METHODS: Plasma biomarkers (interleukin 6 [IL-6] level, D-dimer level, high-sensitivity C-reactive protein [hsCRP] level, soluble CD14 [sCD14] level, and soluble CD163 [sCD163] level) were measured from cryopreserved samples from the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study). We performed immunophenotyping of peripheral blood mononuclear cells for markers of T-cell and monocyte activation, maturation, and migration. We evaluated associations between cellular phenotypes and soluble biomarkers by Spearman rank correlation and multivariate linear regression. RESULTS: Participants' (n = 670) median age was 41 years, 88% were prescribed antiretroviral therapy, 72% had a plasma HIV RNA load of <400 copies/mL, and the median CD4(+) T-lymphocyte count was 471 cells/µL. After adjustment, CD14(++)CD16(+) monocytes were associated with higher levels of IL-6, hsCRP, and sCD163; associations with IL-6 and hsCRP persisted in persons with suppressed HIV replication. While CCR5(+) monocytes positively associated with D-dimer levels, CCR2(+) monocytes were inversely associated with hsCRP levels. CONCLUSIONS: Plasma inflammatory biomarkers that predict morbidity and mortality were strongly associated with monocyte activation and migration, modestly associated with T-cell maturation, and not associated with CD8(+) T-cell activation phenotypes. These findings suggest that strategies to control monocyte activation warrant further investigation.
Subject(s)
HIV Infections/immunology , Inflammation/blood , Monocytes/physiology , Adult , Antigens, CD/blood , Antigens, Differentiation, Myelomonocytic/blood , Biomarkers/blood , Blood Coagulation/physiology , C-Reactive Protein/analysis , Female , Fibrin Fibrinogen Degradation Products/analysis , HIV Infections/blood , HIV Infections/physiopathology , Humans , Inflammation/physiopathology , Interleukin-6/blood , Lipopolysaccharide Receptors/blood , Male , Middle Aged , Phenotype , Receptors, Cell Surface/blood , T-Lymphocytes/physiologyABSTRACT
BACKGROUND: Identifying immunologic mechanisms that contribute to premature cardiovascular disease (CVD) among HIV-positive patients will inform prevention strategies. METHODS: Coronary artery calcium (CAC) progression was studied in an HIV cohort. Immunophenotypes were measured on baseline cryopreserved peripheral blood mononuclear cells using multicolor flow cytometry. Logistic regression identified predictors of CAC progression after adjusting for traditional and HIV-related risk factors. RESULTS: Baseline characteristics for the analysis cohort (n=436) were median age 42 years, median CD4 cell count 481 cells/µl, and 78% receiving antiretroviral therapy. Higher frequencies of CD16 monocytes were associated with greater likelihood of CAC progression, after adjusting for traditional and HIV risk factors [odds ratio per doubling was 1.66 for CD14/CD16 (P=0.02), 1.36 for CD14/CD16 (P=0.06), and 1.69 for CD14/CD16 (P=0.01)]. Associations for CD16 monocytes persisted when restricted to participants with viral suppression. We found no significant associations for CAC progression with other cellular phenotypes, including T-cell activation and senescence markers. CONCLUSION: Circulating CD16 monocytes, potentially reflecting a more pro-atherogenic subpopulation, independently predicted greater CAC progression among HIV-infected persons at low risk for AIDS. In contrast to T-cell abnormalities classically associated with AIDS-related disease progression, these data highlight the potential role of monocyte activation in HIV-related CVD risk.
