title: Exploratory study of oral combination antiviral therapy for hepatitis C.
abstract: BACKGROUND
  There is a need for interferon-free treatment regimens for hepatitis C virus (HCV) infection. The goal of this study was to evaluate ABT-450, a potent HCV NS3 protease inhibitor, combined with low-dose ritonavir (ABT-450/r), in addition to ABT-333, a nonnucleoside NS5B polymerase inhibitor, and ribavirin, for the treatment of HCV infection.
  
  
  METHODS
  We conducted a 12-week, phase 2a, open-label study involving patients who had HCV genotype 1 infection without cirrhosis. All patients received ABT-333 (400 mg twice daily) and ribavirin (1000 to 1200 mg per day) and one of two daily doses of ABT-450/r. Groups 1 and 2 included previously untreated patients; group 1 received 250 mg of ABT-450 and 100 mg of ritonavir, and group 2 received 150 mg and 100 mg, respectively. Group 3, which included patients who had had a null or partial response to previous therapy with peginterferon and ribavirin, received daily doses of 150 mg of ABT-450 and 100 mg of ritonavir. The primary end point was an undetectable level of HCV RNA from week 4 through week 12 (extended rapid virologic response).
  
  
  RESULTS
  A total of 17 of the 19 patients in group 1 (89%) and 11 of the 14 in group 2 (79%) had an extended rapid virologic response; a sustained virologic response 12 weeks after the end of treatment was achieved in 95% and 93% of the patients, respectively. In group 3, 10 of 17 patients (59%) had an extended rapid virologic response, and 8 (47%) had a sustained virologic response 12 weeks after therapy; 6 patients had virologic breakthrough, and 3 had a relapse. Adverse events included abnormalities in liver-function tests, fatigue, nausea, headache, dizziness, insomnia, pruritus, rash, and vomiting.
  
  
  CONCLUSIONS
  This preliminary study suggests that 12 weeks of therapy with a combination of a protease inhibitor, a nonnucleoside polymerase inhibitor, and ribavirin may be effective for treatment of HCV genotype 1 infection. (Funded by Abbott; ClinicalTrials.gov number, NCT01306617.).
authors.affiliation: University of Texas Health Science Center at San Antonio, Division of Gastroenterology and Nutrition (MC7878), 7703 Floyd Curl Dr., San Antonio, TX 78229, USA. poordad@uthscsa.edu
authors.forename: Fred
authors.initials: F
authors.lastname: Poordad
authors.forename: Eric
authors.initials: E
authors.lastname: Lawitz
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Cohen
authors.forename: Thomas
authors.initials: T
authors.lastname: Podsadecki
authors.forename: Sara
authors.initials: S
authors.lastname: Siggelkow
authors.forename: Michele
authors.initials: M
authors.lastname: Heckaman
authors.forename: Lois
authors.initials: L
authors.lastname: Larsen
authors.forename: Rajeev
authors.initials: R
authors.lastname: Menon
authors.forename: Gennadiy
authors.initials: G
authors.lastname: Koev
authors.forename: Rakesh
authors.initials: R
authors.lastname: Tripathi
authors.forename: Tami
authors.initials: T
authors.lastname: Pilot-Matias
authors.forename: Barry
authors.initials: B
authors.lastname: Bernstein
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000378:metabolism; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D011480:Protease Inhibitors; D012367:RNA, Viral; D012254:Ribavirin; D019438:Ritonavir; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase