title: Intensified peginterferon α-2a dosing increases sustained virologic response rates in heavy, high viral load hepatitis C genotype 1 patients with high low-density lipoprotein.
abstract: OBJECTIVE
  Patients infected with hepatitis C virus (HCV) with elevated low-density lipoprotein (LDL) levels achieve higher sustained virologic response (SVR) rates after peginterferon (PegIFN)/ribavirin treatment versus patients with lower LDL. Our aim was to determine whether SVR rates in patients with low/elevated LDL can be improved by dose intensification.
  
  
  METHODS
  In PROGRESS, genotype 1 patients with baseline HCV RNA ≥ 400,000 IU/mL and body weight ≥ 85 kg were randomized to 48 weeks of 180 µg/wk PegIFN α-2a (40 kDa) plus ribavirin (A: 1200 mg/d; B: 1400/1600 mg/d) or 12 weeks of 360 µg/wk PegIFN α-2a followed by 36 weeks of 180 µg/wk, plus ribavirin (C: 1200 mg/d; D: 1400/1600 mg/d). This retrospective analysis assessed SVR rates among patients with low (<100 mg/dL) or elevated (≥ 100 mg/dL) LDL. Patients with high LDL (n=256) had higher baseline HCV RNA (5.86 × 10(6) IU/mL) versus patients with low LDL (n=262; 4.02 × 10(6) IU/mL; P=0.0003).
  
  
  RESULTS
  Multiple logistic regression analysis identified a significant interaction between PegIFN α-2a dose and LDL levels on SVR (P=0.0193). The only treatment-related SVR predictor in the nested multiple logistic regression was PegIFN α-2a dose among patients with elevated LDL (P=0.0074); therefore, data from the standard (A+B) and induction (C+D) dose arms were pooled. Among patients with low LDL, SVR rates were 40% and 35% in the standard and induction-dose groups, respectively; SVR rates in patients with high LDL were 44% and 60% (P=0.014), respectively.
  
  
  CONCLUSIONS
  Intensified dosing of PegIFN α-2a increases SVR rates in patients with elevated LDL even with the difficult-to-cure characteristics of genotype 1, high baseline viral load, and high body weight.
authors.affiliation: Division of Gastroenterology and Hepatology, Brooke Army Medical Center, Fort Sam Houston, San Antonio, TX 78234, USA. stephen.a.harrison@us.army.mil
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Harrison
authors.forename: Djamal
authors.initials: D
authors.lastname: Abdurakhmanov
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Igor
authors.initials: I
authors.lastname: Bakulin
authors.forename: Wlodzimierz
authors.initials: W
authors.lastname: Mazur
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodriguez-Torres
authors.forename: Giovanni Faria
authors.initials: GF
authors.lastname: Silva
authors.forename: Hugo
authors.initials: H
authors.lastname: Cheinquer
authors.forename: Diethelm
authors.initials: D
authors.lastname: Messinger
authors.forename: Edward V
authors.initials: EV
authors.lastname: Connell
authors.forename: Michael
authors.initials: M
authors.lastname: McKenna
authors.forename: Fernando
authors.initials: F
authors.lastname: Tatsch
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001835:Body Weight; D008078:Cholesterol, LDL / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D008078:Cholesterol, LDL; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a