title: Immune biomarker differences and changes comparing HCV mono-infected, HIV/HCV co-infected, and HCV spontaneously cleared patients.
abstract: BACKGROUND
  Immune biomarkers are implicated in HCV treatment response, fibrosis, and accelerated pathogenesis of comorbidities, though only D-dimer and C-reactive protein have been consistently studied. Few studies have evaluated HIV/HCV co-infection, and little longitudinal data exists describing a broader antiviral cytokine response.
  
  
  METHODS
  Fifty immune biomarkers were analyzed at baseline (BL) and HCV end of treatment follow-up(FU) time point using the Luminex 50-plex assay in plasma samples from 15 HCV-cleared, 24 HCV mono- and 49 HIV/HCV co-infected patients receiving antiretroviral treatment, who either did or did not receive pegylated-interferon/ribavirin HCV treatment. Biomarker levels were compared among spontaneous clearance patients, mono- and co-infected, untreated and HCV-treated, and sustained virologic responders (SVR) and non-responders (NR) at BL and FU using nonparametric analyses. A Bonferroni correction, adjusting for tests of 50 biomarkers, was used to reduce Type I error.
  
  
  RESULTS
  Compared to HCV patients at BL, HIV/HCV patients had 22 significantly higher and 4 significantly lower biomarker levels, following correction for multiple testing. There were no significantly different BL levels when comparing SVR and NR in mono- or co-infected patients; however, FU levels changed considerably in co-infected patients, with seven becoming significantly higher and eight becoming significantly lower in SVR patients. Longitudinally between BL and FU, 13 markers significantly changed in co-infected SVR patients, while none significantly changed in co-infected NR patients. There were also no significant changes in longitudinal analyses of mono-infected patients achieving SVR or mono-infected and co-infected groups deferring treatment.
  
  
  CONCLUSIONS
  Clear differences exist in pattern and quantity of plasma immune biomarkers among HCV mono-infected, HIV/HCV co-infected, and HCV-cleared patients; and with SVR in co-infected patients treated for HCV. Though >90% of patients were male and co-infected had a larger percentage of African American patients, our findings may have implications for better understanding HCV pathogenesis, treatment outcomes, and future therapeutic targets.
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Palo Alto, California, United States of America.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Kushner
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Wendelboe
authors.forename: Laura C
authors.initials: LC
authors.lastname: Lazzeroni
authors.forename: Aarthi
authors.initials: A
authors.lastname: Chary
authors.forename: Mark A
authors.initials: MA
authors.lastname: Winters
authors.forename: Anu
authors.initials: A
authors.lastname: Osinusi
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
authors.forename: Michael A
authors.initials: MA
authors.lastname: Polis
authors.forename: Mark
authors.initials: M
authors.lastname: Holodniy
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D060085:Coinfection; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D016207:Cytokines