Biomarkers of microbial translocation and macrophage activation: association with progression of subclinical atherosclerosis in HIV-1 infection

J Infect Dis. 2012 Nov 15;206(10):1558-67. doi: 10.1093/infdis/jis545. Epub 2012 Oct 12.

Abstract

Background: The relationships between soluble CD14 (sCD14), endotoxin (lipopolysaccharide [LPS]), and progression of atherosclerosis have not been defined in human immunodeficiency virus (HIV) infection.

Methods: We retrospectively assessed serum sCD14 and LPS levels of 91 subjects in a prospective 3-year study of carotid artery intima-media thickness (CIMT) (AIDS Clinical Trials Group [ACTG] 5078), where subjects were enrolled as risk factor-controlled triads of HIV-uninfected (n = 36) and HIV-infected individuals with (n = 29) or without (n = 26) protease inhibitor (PI)-based therapy for ≥2 years. The primary end point was the yearly rate of change of CIMT (ΔCIMT).

Results: In multivariate analysis of the HIV-infected subjects, each 1 µg/mL above the mean of baseline serum sCD14 corresponded to an additional 1.52 µm/y (95% confidence interval, .07-2.98; P = .04) in the ΔCIMT. Every 100 pg/mL above the mean of baseline serum LPS corresponded to an additional 0.49 µm/y (95% confidence interval, .18-.81; P = .003) in the ΔCIMT. However, in univariate analysis in the HIV-uninfected group sCD14 (P = .33) and LPS (P = .27) levels were not associated with higher ΔCIMT. HIV infection and PI therapy were not associated with baseline serum LPS and sCD14 levels (P > .1).

Conclusions: Our data are among the first to suggest that serum biomarkers of microbial translocation (LPS) and macrophage activation (sCD14) predict subclinical atherosclerosis progression in HIV-infected persons.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use
  • Atherosclerosis / complications*
  • Bacterial Translocation
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Cohort Studies
  • Female
  • HIV Infections / blood
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV-1*
  • Humans
  • Lipopolysaccharide Receptors / blood*
  • Lipopolysaccharide Receptors / metabolism
  • Lipopolysaccharides / blood*
  • Lipopolysaccharides / metabolism
  • Macrophage Activation / physiology*
  • Male
  • Middle Aged
  • Protease Inhibitors / therapeutic use
  • Retrospective Studies

Substances

  • Anti-HIV Agents
  • Biomarkers
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Protease Inhibitors