title: Low-density lipoprotein receptor genotyping enhances the predictive value of IL28B genotype in HIV/hepatitis C virus-coinfected patients.
abstract: OBJECTIVE
  The aims of this study were to appraise the predictive value of variations in a single-nucleotide polymorphism (SNP) in the low-density lipoprotein receptor (LDLR) gene for sustained virological response (SVR) to pegylated interferon (Peg-IFN) and ribavirin (RBV), as well as to analyze the relationship between LDLR genotype and other predictors of SVR, particularly IL28B genotype, in patients coinfected with HIV and hepatitis C virus (HCV).
  
  
  METHODS
  One hundred and eighty-four HIV/HCV-coinfected, treatment-naive patients with chronic HCV infection, who received Peg-IFN and RBV, were included. Variations in the SNP rs14158 and rs12979860 were tested by Taqman PCR assay.
  
  
  RESULTS
  Twenty-eight (38%) patients with rs14158 TT/TC and 61 (55%) with CC (P = 0.028) achieved SVR. The rates of SVR in patients with rs14158 TT/TC and with CC harboring HCV 1-4 were 20 and 41% (P = 0.020), respectively, and, in those with HCV genotype 2-3, 75 and 84% (P = 0.513), respectively. Patients with rs14158 CC showed less commonly plasma HCV-RNA load at least 600000 IU/ml (57 vs. 71%, P = 0.047) and lower likelihood of relapse (13 vs. 30%, P = 0.023). In patients with HCV genotype 1-4, the rates of SVR according to the combination of IL28B/LDLR genotypes were: CC/CC = 69%; CC/non-CC: 30%; non-CC/CC: 25%; non-CC/non-CC: 14% (P < 0.001).
  
  
  CONCLUSIONS
  Variations in rs14158 are associated with SVR to Peg-IFN and RBV in HIV/HCV-coinfected patients harboring HCV genotype 1-4. LDLR and IL28B genotypes seem to have a synergistic effect on SVR. The combined use of LDLR and IL28B genotypes in routine clinical practice could enhance the predictive value of IL28B genotype alone.
authors.affiliation: Unit of Infectious Diseases and Microbiology, Hospital Universitario de Valme, Seville, Spain. japineda@telefonica.net
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
authors.forename: Antonio
authors.initials: A
authors.lastname: Caruz
authors.forename: Federico A
authors.initials: FA
authors.lastname: Di Lello
authors.forename: Angela
authors.initials: A
authors.lastname: Camacho
authors.forename: Pilar
authors.initials: P
authors.lastname: Mesa
authors.forename: Karin
authors.initials: K
authors.lastname: Neukam
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero-juárez
authors.forename: Juan
authors.initials: J
authors.lastname: Macías
authors.forename: Jesús
authors.initials: J
authors.lastname: Gómez-Mateos
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000235:genetics*; D000328:Adult; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000187:drug effects; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D011092:Polyethylene Glycols; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000235:genetics*; D011973:Receptors, LDL / Q000187:drug effects / Q000235:genetics*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011973:Receptors, LDL; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b