Monocyte-activation phenotypes are associated with biomarkers of inflammation and coagulation in chronic HIV infection

J Infect Dis. 2014 Nov 1;210(9):1396-406. doi: 10.1093/infdis/jiu275. Epub 2014 May 9.


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.

Keywords: C-reactive protein; D-dimer; HIV; IL-6; immune activation; monocytes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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 / immunology*
  • HIV Infections / physiopathology
  • Humans
  • Inflammation / blood*
  • Inflammation / physiopathology
  • Interleukin-6 / blood
  • Lipopolysaccharide Receptors / blood
  • Male
  • Middle Aged
  • Monocytes / physiology*
  • Phenotype
  • Receptors, Cell Surface / blood
  • T-Lymphocytes / physiology


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers
  • CD163 antigen
  • Fibrin Fibrinogen Degradation Products
  • Interleukin-6
  • Lipopolysaccharide Receptors
  • Receptors, Cell Surface
  • fibrin fragment D
  • C-Reactive Protein