title: Circulating sCD14 is associated with virological response to pegylated-interferon-alpha/ribavirin treatment in HIV/HCV co-infected patients.
abstract: OBJECTIVE
  Microbial translocation (MT) through the gut accounts for immune activation and CD4+ loss in HIV and may influence HCV disease progression in HIV/HCV co-infection. We asked whether increased MT and immune activation may hamper anti-HCV response in HIV/HCV patients.
  
  
  METHODS
  98 HIV/HCV patients who received pegylated-alpha-interferon (peg-INF-alpha)/ribavirin were retrospectively analyzed. Baseline MT (lipopolysaccharide, LPS), host response to MT (sCD14), CD38+HLA-DR+CD4+/CD8+, HCV genotype, severity of liver disease were assessed according to Early Virological Response (EVR: HCV-RNA <50 IU/mL at week 12 of therapy or ≥2 log(10) reduction from baseline after 12 weeks of therapy) and Sustained Virological Response (SVR: HCV-RNA <50 IU/mL 24 weeks after end of therapy). Mann-Whitney/Chi-square test and Pearson's correlation were used. Multivariable regression was performed to determine factors associated with EVR/SVR.
  
  
  RESULTS
  71 patients displayed EVR; 41 SVR. Patients with HCV genotypes 1-4 and cirrhosis presented a trend to higher sCD14, compared to patients with genotypes 2-3 (p = 0.053) and no cirrhosis (p = 0.052). EVR and SVR patients showed lower levels of circulating sCD14 (p = 0.0001, p = 0.026, respectively), but similar T-cell activation compared to Non-EVR (Null Responders, NR) and Non-SVR (N-SVR) subjects. sCD14 resulted the main predictive factor of EVR (0.145 for each sCD14 unit more, 95%CI 0.031-0.688, p = 0.015). SVR was associated only with HCV genotypes 2-3 (AOR 0.022 for genotypes 1-4 vs 2-3, 95%CI 0.001-0.469, p = 0.014).
  
  
  CONCLUSIONS
  In HIV/HCV patients sCD14 correlates with the severity of liver disease and predicts early response to peg-INF-alpha/ribavirin, suggesting MT-driven immune activation as pathway of HIV/HCV co-infection and response to therapy.
authors.affiliation: Department of Medicine, Surgery and Dentistry, Clinic of Infectious Diseases and Tropical Medicine, University of Milan, San Paolo Hospital, Milan, Italy. giulia.marchetti@unimi.it
authors.forename: Giulia
authors.initials: G
authors.lastname: Marchetti
authors.forename: Paola
authors.initials: P
authors.lastname: Nasta
authors.forename: Francesca
authors.initials: F
authors.lastname: Bai
authors.forename: Francesca
authors.initials: F
authors.lastname: Gatti
authors.forename: Giusi Maria
authors.initials: GM
authors.lastname: Bellistrì
authors.forename: Camilla
authors.initials: C
authors.lastname: Tincati
authors.forename: Federica
authors.initials: F
authors.lastname: Borghi
authors.forename: Giampiero
authors.initials: G
authors.lastname: Carosi
authors.forename: Massimo
authors.initials: M
authors.lastname: Puoti
authors.forename: Antonella d'Arminio
authors.initials: Ad
authors.lastname: Monforte
mesh_terms: D000328:Adult; D001419:Bacteria / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D060085:Coinfection / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D003710:Demography; D005260:Female; D005355:Fibrosis / Q000150:complications / Q000382:microbiology / Q000821:virology; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D006684:HLA-DR Antigens / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008070:Lipopolysaccharides / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D012995:Solubility / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006684:HLA-DR Antigens; D016898:Interferon-alpha; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a