title: Plasma IL-6 levels are independently associated with atherosclerosis and mortality in HIV-infected individuals on suppressive antiretroviral therapy.
abstract: To determine the associations of markers of immune activation with atherosclerosis and mortality, in participants with treated and suppressed HIV infection.
  
  
  
  Observational study of 149 HIV-infected participants with virologic suppression on antiretroviral therapy.
  
  
  
  Cryopreserved mononuclear cells and plasma were used to evaluate markers of T cell and monocyte activation, inflammation and coagulopathy. Carotid artery intima-media thickness (CIMT) was measured by high-resolution ultrasound at the common, bifurcation and internal carotid regions. Associations of immunologic markers with CIMT and all-cause mortality were assessed using multivariable linear regression and Cox proportional hazards regression.
  
  
  
  The majority of participants were men (93%) and white (67%), median age of 48.5 years and median CD4 T-cell count of 522 cells/μl. The median baseline IMT was 1.0 mm. Over a median of 8.3-year follow-up, 12 deaths occurred. In multivariate analysis, adjusted for traditional cardiovascular risk factors, higher monocyte C-C motif chemokine receptor 5 (CCR5) expression [5.4%, P = 0.001] was associated with greater common CIMT. Higher plasma IL-6 was associated with greater bifurcation [8.0%, P = 0.007] and overall mean IMT [5.2%, P = 0.026]. Finally, higher plasma IL-6 [hazard ratio 1.9, P = 0.030], internal carotid [hazard ratio 4.1, P = 0.022] and mean IMT [hazard ratio 5.2, P = 0.026] were individually associated with all-cause mortality.
  
  
  
  Higher monocyte CCR5 expression and plasma IL-6 were associated with atherosclerosis, independent of traditional cardiovascular risk factors. IL-6 and CIMT were individually associated with all-cause mortality. The impact of therapies targeting immune activation in cardiovascular disease in treated HIV infection merits additional investigation.
authors.affiliation: aNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland bUniversity of California San Francisco (UCSF), San Francisco, California cLeidos Biomedical Research, Inc, Frederick, Maryland dUniversity of California and Veterans Affairs Medical Center, San Francisco, California, USA. *These two authors contributed equally to this work.
authors.forename: Denise C
authors.initials: DC
authors.lastname: Hsu
authors.forename: Yi Fei
authors.initials: YF
authors.lastname: Ma
authors.forename: Sophia
authors.initials: S
authors.lastname: Hur
authors.forename: Danny
authors.initials: D
authors.lastname: Li
authors.forename: Adam
authors.initials: A
authors.lastname: Rupert
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scherzer
authors.forename: S C
authors.initials: SC
authors.lastname: Kalapus
authors.forename: Steven
authors.initials: S
authors.lastname: Deeks
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.forename: Priscilla Y
authors.initials: PY
authors.lastname: Hsue
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000175:diagnosis* / Q000473:pathology*; D016893:Carotid Stenosis / Q000000981:diagnostic imaging; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000401:mortality*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D019713:Receptors, CCR5 / Q000032:analysis; D000072230:Sustained Virologic Response; D014463:Ultrasonography
chemical_list: D044966:Anti-Retroviral Agents; C584933:CCR5 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D019713:Receptors, CCR5