Biomarkers of Microbial Translocation and Macrophage Activation: Association With Progression of Subclinical Atherosclerosis in HIV-1 Infection

• Published in: The Journal of infectious diseases Vol. 206; no. 10; pp. 1558 - 1567
• Main Authors: Kelesidis, Theodoros, Kendall, Michelle A., Yang, Otto O., Hodis, Howard N., Currier, Judith S.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.11.2012
• Subjects: Adult; AIDS; Anti-HIV Agents - therapeutic use; Atherosclerosis; Atherosclerosis - complications; Bacterial Translocation; Biological and medical sciences; Biomarkers - blood; Biomarkers - metabolism; Body mass index; Cholesterols; Cohort Studies; Female; Fundamental and applied biological sciences. Psychology; HDL lipoproteins; HIV; HIV infections; HIV Infections - blood; HIV Infections - complications; HIV Infections - drug therapy; HIV-1; HIV/AIDS; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; Lipopolysaccharide Receptors - blood; Lipopolysaccharide Receptors - metabolism; Lipopolysaccharides - blood; Lipopolysaccharides - metabolism; Macrophage Activation - physiology; Major and Brief Reports; Male; Medical sciences; Memory interference; Microbiology; Middle Aged; Miscellaneous; Modeling; Protease Inhibitors - therapeutic use; Rates of change; Retrospective Studies; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology; Immunopathology; HIV-1 virus; Retroviridae; Biological marker; Cardiovascular disease; AIDS; Immune deficiency; Lentivirus; Vascular disease; Virus; Infection; Viral disease; Atherosclerosis; Human immunodeficiency virus; Macrophage
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jis545

Background. The relationships between soluble CD 14 (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 (∆CIMT). 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 ∆CIMT. 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 ∆CIMT. However, in univariate analysis in the HIV-uninfected group sCD14 (P = .33) and LPS (P = .27) levels were not associated with higher ∆CIMT. 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.