title: IL28B polymorphism, pretreatment CXCL10, and HCV RNA levels predict treatment response in racially diverse HIV/HCV coinfected and HCV monoinfected patients.
abstract: OBJECTIVE
  We sought to develop a score to predict sustained virological response (SVR) in racially diverse HIV/hepatitis C virus (HCV)-coinfected and HCV-monoinfected pegylated interferon/ribavirin-treated patients.
  
  
  METHODS
  We retrospectively evaluated 374 patients (259 monoinfected and 115 coinfected) treated at a single tertiary care center. The IL28B rs12979860 single nucleotide polymorphism genotyping was performed in 335 patients, and plasma CXCL10 levels were measured by enzyme-linked immunosorbent assay in 171 patients.
  
  
  RESULTS
  Of the 374 patients, 64.9% were white, 17.2% were African American, 76.5% were HCV genotype 1 infected, and 49.3% had advanced fibrosis. Sustained virological response was achieved by 151 (40.4%) patients, 106 (40.9%) patients monoinfected, and 45 (39.1%) patients coinfected. Patients with IL28B C/C genotype were significantly more likely to achieve an SVR compared with non-C/C genotype patients, but only if they were infected with HCV genotypes 1/4 (59.1% vs 21.1%, P < 0.0001). No significant differences existed in IL28B predictive capacity between coinfected and monoinfected patients. Pretreatment CXCL10 levels were significantly higher in nonresponders, both monoinfected and coinfected, compared with SVR patients (P = 0.0018). Coinfected patients had higher CXCL10 levels compared with monoinfected patients (P = 0.03). The combination of IL28B genotype, pretreatment CXCL10 and HCV RNA levels, and HCV genotype had the best ability to predict treatment response in both patient groups (area under the receiver operating characteristic curve = 0.85). Among all patients, a cutoff score of -0.94 or more had a sensitivity of 0.93 and specificity of 0.59. In coinfected patients, a score of -0.55 or more had sensitivity of 0.81 and specificity of 0.80.
  
  
  CONCLUSIONS
  IL28B genotype, pretreatment CXCL10, and HCV RNA levels have very good capacity to predict pegylated interferon/ribavirin-treatment outcome in both HIV/HCV coinfected and HCV monoinfected patients.
authors.affiliation: Center for the Study of Hepatitis C and Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY 10065, USA. maz2003@med.cornell.edu
authors.forename: Marija
authors.initials: M
authors.lastname: Zeremski
authors.forename: Rositsa B
authors.initials: RB
authors.lastname: Dimova
authors.forename: Jessy
authors.initials: J
authors.lastname: Makeyeva
authors.forename: John D
authors.initials: JD
authors.lastname: Sipley
authors.forename: Ira M
authors.initials: IM
authors.lastname: Jacobson
authors.forename: Hanna
authors.initials: H
authors.lastname: Rennert
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Talal
mesh_terms: D000328:Adult; D001741:Black or African American; D000998:Antiviral Agents / Q000627:therapeutic use*; D044383:Black People; D054357:Chemokine CXCL10 / Q000097:blood*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000208:ethnology / Q000821:virology; D015497:HIV-1; D016174:Hepacivirus / Q000235:genetics* / Q000502:physiology; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000208:ethnology / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood*; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D044465:White People; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D054357:Chemokine CXCL10; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D012254:Ribavirin; C114753:CXCL10 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda