title: Prediction of response to pegylated interferon plus ribavirin in HIV/hepatitis C virus (HCV)-coinfected patients using HCV genotype, IL28B variations, and HCV-RNA load.
abstract: OBJECTIVE
  This study aimed at developing a predictive algorithm based on interleukin 28B (IL28B) genotype, hepatitis C virus (HCV) genotype, and plasma HCV-RNA load, which could accurately allow us to define the probability of response to pegylated interferon (Peg-IFN) plus ribavirin (RBV) therapy in HIV/HCV-coinfected patients.
  
  
  METHODS
  Five hundred and twenty-one treatment-naive HIV-infected patients, who initiated HCV therapy with Peg-IFN/RBV, were analysed in an on-treatment basis. Patients were categorized as unlikely responders, uncertain responders, and anticipated responders (<20%, 20-60%, and >60% probability to achieve SVR, respectively).
  
  
  RESULTS
  HCV genotype, baseline HCV-RNA load, and IL28B genotype were confirmed as independent predictors of SVR in a logistic regression analysis. A stepwise algorithm based on these three variables was created based on 321 patients and evaluated in the remaining 200 patients. Unlikely responders included patients with genotype 1 or 4, HCV-RNA load ≥600,000IU/ml, and rs12979860 non-CC (rate of SVR: 17.3%). Anticipated responders were those with HCV genotype 2-3, patients harboring HCV genotype 4 and IL28B CC, as well as those who simultaneously bore HCV genotype 1, HCV-RNA load <600,000IU/ml, and IL28B CC (rate of SVR 74.1%, 77.8%, and 64.4%, respectively). The area under the receiver operating characteristic curve of the model was 0.77 (0.733-0.814).
  
  
  CONCLUSIONS
  The combined use of IL28B genotype, HCV genotype, and HCV-RNA load enables to easily identify patients with a high and very low likelihood of SVR. HCV therapy could be deferred in the latter patients, until more effective options are available, at least if they do not show advanced liver fibrosis.
authors.affiliation: Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville, Spain.
authors.forename: Karin
authors.initials: K
authors.lastname: Neukam
authors.forename: Angela
authors.initials: A
authors.lastname: Camacho
authors.forename: Antonio
authors.initials: A
authors.lastname: Caruz
authors.forename: Norma
authors.initials: N
authors.lastname: Rallón
authors.forename: Almudena
authors.initials: A
authors.lastname: Torres-Cornejo
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Rockstroh
authors.forename: Juan
authors.initials: J
authors.lastname: Macías
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
authors.forename: José M
authors.initials: JM
authors.lastname: Benito
authors.forename: Luis F
authors.initials: LF
authors.lastname: López-Cortés
authors.forename: Jacob
authors.initials: J
authors.lastname: Nattermann
authors.forename: Jesús
authors.initials: J
authors.lastname: Gómez-Mateos
authors.forename: Vicente
authors.initials: V
authors.lastname: Soriano
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
mesh_terms: D000328:Adult; D000465:Algorithms; D000998:Antiviral Agents / Q000627:therapeutic use; D015331:Cohort Studies; D015897:Comorbidity; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012044:Regression Analysis; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a