title: Relationship between microbial translocation and endothelial function in HIV infected patients.
abstract: BACKGROUND
  Circulating levels of microbial products are increased in HIV infection, and provoke endothelial dysfunction in other disease settings.
  
  
  RESULTS
  We examined data from a cross-sectional single site study at Indiana University (Indiana, N = 85) and a 24- week multicenter prospective study of antiretroviral therapy (ART) initiation (ACTG 5152s, N = 75). Brachial artery flow-mediated dilation (FMD) was measured by ultrasound. Plasma lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels were measured from stored specimens and correlated with FMD values using Pearson correlations. The Indiana subjects were 63% male with a mean age of 39 years and a median CD4 count of 406 cells/mm(3) (388 not on ART, 464 on ART). The 5152s subjects were 92% were male with a mean age of 35 years and a median CD4 count of 251 cells/mm(3) at entry which increased to 396 cells/mm(3) on ART. When analyzing the two cohorts individually or in combination neither sCD14 nor LPS correlated significantly with FMD. In a pre-specified subgroup analysis of the Indiana subjects receiving ART (N = 46, mean ART duration 40 months) LPS was inversely correlated with FMD (r = -0.33, p = 0.02), but not sCD14 (r = -0.01, p = 0.9). Multivariate analysis confirmed LPS as an independent predictor of FMD in this subgroup (p = 0.02).
  
  
  CONCLUSIONS
  In HIV-infected individuals on prolonged ART, higher LPS levels are associated with worse endothelial function but not in untreated subjects or at 24 weeks after ART initiation. Persistent microbial translocation may contribute to arterial dysfunction and the increased cardiovascular disease risk observed in individuals on long-term ART.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Southern California Keck School of Medicine, Los Angeles, California, United States of America. eblodget@usc.edu
authors.forename: Emily
authors.initials: E
authors.lastname: Blodget
authors.forename: Changyu
authors.initials: C
authors.lastname: Shen
authors.forename: Grace
authors.initials: G
authors.lastname: Aldrovandi
authors.forename: Adrienne
authors.initials: A
authors.lastname: Rollie
authors.forename: Samir K
authors.initials: SK
authors.lastname: Gupta
authors.forename: James H
authors.initials: JH
authors.lastname: Stein
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dubé
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D001692:Biological Transport; D001916:Brachial Artery / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000150:complications / Q000209:etiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004727:Endothelium / Q000382:microbiology / Q000503:physiopathology* / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000382:microbiology / Q000503:physiopathology*; D006801:Humans; D007196:Indiana; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000097:blood / Q000378:metabolism; D008297:Male; D015999:Multivariate Analysis; D011446:Prospective Studies; D014463:Ultrasonography / Q000379:methods
chemical_list: D044966:Anti-Retroviral Agents; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides