Biomarkers of microbial translocation and macrophage activation: association with progression of subclinical atherosclerosis in HIV-1 infection.
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.
Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA 90035, USA.
Theodoros
T
Kelesidis
Michelle A
MA
Kendall
Otto O
OO
Yang
Howard N
HN
Hodis
Judith S
JS
Currier
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000150:complications*; D018988:Bacterial Translocation; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D015497:HIV-1; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood* / Q000378:metabolism; D008262:Macrophage Activation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000627:therapeutic use; D012189:Retrospective Studies
D019380:Anti-HIV Agents; D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011480:Protease Inhibitors