title: Biomarkers of inflammation, coagulation and microbial translocation in HIV/HCV co-infected patients in the SMART study.
abstract: BACKGROUND
  Previous results from the SMART study showed that HIV/viral hepatitis co-infected persons with impaired liver function are at increased risk of death following interruption of antiretroviral therapy (ART).
  
  
  OBJECTIVE
  To investigate the influence of fibrosis and ART interruption on levels of biomarkers of inflammation, coagulation and microbial translocation in HIV/HCV co-infected persons in the SMART study.
  
  
  METHODS
  All HIV/HCV co-infected persons with stored plasma at study entry and at six months of follow-up were included (N=362). D-dimer, IL-6, sCD14 and hepatic synthesized coagulation markers were measured and compared according to the liver fibrosis marker hyaluronic acid (HA) at study entry. Percent difference in changes in biomarker levels from study entry to month 6 was compared between randomization groups and according to study entry HA levels.
  
  
  RESULTS
  At study entry, persons with elevated HA (>75ng/mL vs. ≤75ng/mL) had higher median (IQR) levels of IL-6 [4.14pg/mL (2.60-6.32) vs. 2.74pg/mL (1.88-3.97)] and soluble CD14 [2163ng/mL (1952-2916) vs. 1979ng/mL (1742-2310)] (p<0.001). Elevated HA was also associated with alterations of both pro- and anti-coagulation markers but the overall coagulation profile was not affected. Interruption of ART lead to a particularly pronounced increase in IL-6 levels in persons with elevated HA levels (p=0.01 for interaction between randomization group and continuous HA level).
  
  
  CONCLUSIONS
  HIV/HCV co-infected persons with impaired liver function are in an enhanced pro-inflammatory state which is further exacerbated upon interruption of ART.
authors.affiliation: CHIP, Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital/Rigshospitalet, Copenhagen, Denmark. Electronic address: lpe@cphiv.dk.
authors.forename: Lars
authors.initials: L
authors.lastname: Peters
authors.affiliation: University of Minnesota, School of Public Health, MN, United States.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Neuhaus
authors.affiliation: University of Minnesota, Cardiovascular Division, MN, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Duprez
authors.affiliation: University of Minnesota, School of Public Health, MN, United States.
authors.forename: James D
authors.initials: JD
authors.lastname: Neaton
authors.affiliation: University of Vermont College of Medicine, VT, United States.
authors.forename: Russel
authors.initials: R
authors.lastname: Tracy
authors.affiliation: Montreal Chest Institute, McGill University Health Centre, Montreal, Canada.
authors.forename: Marina B
authors.initials: MB
authors.lastname: Klein
authors.affiliation: University College London Medical School, Royal Free Campus, United Kingdom.
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
authors.affiliation: Medizinische Universitätsklinik, Bonn, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rockstroh
authors.affiliation: National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia.
authors.forename: Gregory
authors.initials: G
authors.lastname: Dore
authors.affiliation: CHIP, Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital/Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D018791:CD4 Lymphocyte Count; D060085:Coinfection; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000821:virology*; D006526:Hepatitis C / Q000097:blood* / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D018836:Inflammation Mediators; D006820:Hyaluronic Acid
keywords: Coagulation; HIV; Hepatitis; Inflammation; Microbial translocation