title: Influence of Hepatitis C Virus Sustained Virological Response on Immunosuppressive Tryptophan Catabolism in ART-Treated HIV/HCV Coinfected Patients.
abstract: BACKGROUND
  We previously reported an association between tryptophan (Trp) catabolism and immune dysfunction in HIV monoinfection. Coinfection with HIV is associated with more rapid evolution of hepatitis C virus (HCV)-associated liver disease despite antiretroviral therapy (ART), possibly due to immune dysregulation. We hypothesized that liver fibrosis in HIV/HCV coinfection would be associated with immune dysfunction and alterations in Trp metabolism.
  
  
  METHODS
  Trp catabolism and inflammatory soluble markers were assessed in plasma samples from ART-treated HIV/HCV-coinfected patients (n = 90) compared with ART-treated HIV-monoinfected patients and noninfected subjects. Furthermore, 17 additional coinfected patients with sustained virological response (SVR) were assessed longitudinally 6 months after completion of interferon-α/ribavirin treatment.
  
  
  RESULTS
  HIV/HCV patients had higher Trp catabolism compared with HIV-monoinfected and healthy individuals. Elevated kynurenine levels in HIV/HCV patients with liver fibrosis correlated with the prognostic aspartate aminotransaminase to platelet ratio (APRI scores) and insulin levels. Furthermore, HIV/HCV patients had elevated levels of disease progression markers interleukin-6 and induced protein 10 and shared similar levels of markers of microbial translocation (intestinal fatty acid-binding protein, soluble CD14 and lipopolysaccharide-binding protein) compared with HIV-monoinfected and healthy individuals. Successful HCV treatment improved APRI score and markers of disease progression and microbial translocation although elevated Trp catabolism remained unchanged 6 months after SVR.
  
  
  CONCLUSIONS
  ART-treated HIV/HCV-coinfected patients had elevated immunosuppressive Trp catabolism when compared with monoinfected HIV-treated patients, which did not normalize after SVR. These findings suggest that a necroinflammatory liver syndrome persists through inflammation by Trp catabolism after 6 month of SVR.
authors.affiliation: *Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, Quebec, Canada; †Currently, Département des Sciences Biologiques et Centre de recherche BioMed, Université du Québec à Montréal (UQAM), Québec, Canada; ‡Research Institute McGill University Health Centre, Montreal, Quebec, Canada; §Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; ‖Research Department, School of Medicine, Universidad Iberoamericana, Santo Domingo, Dominican Republic; and ¶Division of Hematology, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Jenabian
authors.forename: Vikram
authors.initials: V
authors.lastname: Mehraj
authors.forename: Cecilia T
authors.initials: CT
authors.lastname: Costiniuk
authors.forename: Kishanda
authors.initials: K
authors.lastname: Vyboh
authors.forename: Ido
authors.initials: I
authors.lastname: Kema
authors.forename: Kathleen
authors.initials: K
authors.lastname: Rollet
authors.forename: Robert
authors.initials: R
authors.lastname: Paulino Ramirez
authors.forename: Marina B
authors.initials: MB
authors.lastname: Klein
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D060085:Coinfection; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007737:Kynurenine / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D007328:Insulin; D007737:Kynurenine; D014364:Tryptophan