title: Low levels of microbial translocation marker LBP are associated with sustained viral response after anti-HCV treatment in HIV-1/HCV co-infected patients.
abstract: BACKGROUND
  Microbial translocation (MT) contributes to immune activation during HIV and HCV infections. We investigated the kinetics of MT markers during anti-HCV and anti-HIV treatments, and if baseline plasma levels of lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) could predict anti-HCV treatment outcome.
  
  
  METHODS
  Plasma from 78 HIV-infected patients was evaluated for LPS, LBP and sCD14. The patients starting anti-HCV treatment (with ongoing antiretroviral (ART) treatment) were categorized into sustained viral responders (SVR; n = 21) or non-responders (NR; n = 15) based on treatment outcome. ART starting subjects--were categorized into chronically HCV-infected (CH; n = 24) and mono-infected (HIV; n = 18), based on the HCV infection status. Samples were collected before start (at baseline) of pegylated-interferon-alpha/ribavirin (peg-IFN/RBV) or antiretroviral-therapy and two years after treatment start (at follow up). χ2-test, non-parametric statistics and logistic regression were applied to determine the associations with treatment response and changes of the soluble markers.
  
  
  RESULTS
  Plasma levels of LPS and sCD14 were elevated in all subjects before antiviral-treatment but remained unchanged at follow-up. Elevated levels of LBP were present in patients with HIV and HIV/HCV co-infection and were reduced by ART. Additionally, higher levels of LBP were present at baseline in NR vs. SVR. Higher levels of LBP at baseline were associated with non-response to peg-IFN/RBV treatment in both bivariate (OR: 0.19 95% CI: 0.06-0.31, p = 0.004) and multivariate analysis (OR: 1.43, 95% CI: 1.1-1.86, p = 0.07).
  
  
  CONCLUSIONS
  In HIV/HCV co-infected patients high baseline LBP levels are associated with non-response to peg-IFN/RBV therapy. Plasma LBP (decreased by ART) may be a more relevant MT marker than LPS and sCD14.
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Jessica
authors.initials: J
authors.lastname: Nyström
authors.affiliation: Unit of Infectious Diseases, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Stenkvist
authors.affiliation: Unit of Infectious Diseases, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden; Department of Infectious Diseases, County Council of Gävleborg, Gävle, Sweden.
authors.forename: Amanda
authors.initials: A
authors.lastname: Häggblom
authors.affiliation: Unit of Infectious Diseases, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Weiland
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden; Unit of Infectious Diseases, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Piotr
authors.initials: P
authors.lastname: Nowak
mesh_terms: D000209:Acute-Phase Proteins; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000097:blood*; D060085:Coinfection / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D007700:Kinetics; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000737:chemistry; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D012189:Retrospective Studies; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use; D012995:Solubility; D013997:Time Factors; D016896:Treatment Outcome; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D019380:Anti-HIV Agents; D001219:Aspartate Aminotransferases; D015415:Biomarkers; D002352:Carrier Proteins; D016898:Interferon-alpha; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012254:Ribavirin; D000099231:Lipopolysaccharide-Binding Protein