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

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

Author information

1
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
2
Division of Biostatistics.
3
Washington University School of Medicine, St. Louis, Missouri.
4
Department of Medicine, University of Minnesota Washington University School of Medicine, St. Louis, Missouri.
5
National Jewish Health, Denver, Colorado.
6
Miriam Hospital, Providence, Rhode Island.
7
Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
8
Department of Medicine, University of Minnesota Division of Infectious Diseases, Hennepin County Medical Center, Minneapolis, Minnesota.

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.

KEYWORDS:

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

PMID:
24813472
PMCID:
PMC4207864
DOI:
10.1093/infdis/jiu275
[Indexed for MEDLINE]
Free PMC Article

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