title: Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With or Without Ribavirin in HCV-Infected Patients Taking Concomitant Acid-Reducing Agents.
abstract: Acid-reducing agents (ARAs) and proton-pump inhibitors (PPIs) that increase gastric pH can alter the bioavailability of antiviral drugs, particularly relevant in patients with advanced liver disease caused by chronic hepatitis C virus (HCV) infection seeking therapy. Using integrated data from six phase 3 studies, we report the safety and efficacy of the 3-direct-acting antiviral (DAA) regimen containing ombitasvir (OBV, an NS5A inhibitor), ritonavir-boosted paritaprevir (PTV/r, an NS3/4A protease inhibitor), and dasabuvir (DSV, an NS5B polymerase inhibitor) with or without ribavirin (RBV) for HCV genotype 1 patients taking concomitant ARAs and PPIs.
  
  
  
  Treatment-naïve or peginterferon/RBV treatment-experienced patients with or without compensated cirrhosis received OBV/PTV/r and DSV with or without weight-based RBV. Rates of sustained virologic response (SVR), defined as HCV RNA below the lower limit of quantification, 12 weeks post-treatment (SVR12) and safety were evaluated in patients who were receiving concomitant ARAs.
  
  
  
  Among 2,053 patients enrolled and dosed with study drug, 410 (20%) were receiving concomitant ARAs; of these, 308 (15%) were taking concomitant PPIs. Rates of SVR12 were 95.9% (95% confidence interval (CI) 93.5-97.4%) among patients receiving an ARA, and 96.3% (95% CI 95.3-97.2%) in patients not receiving a concomitant ARA. Similarly, among patients receiving a PPI or not, SVR12 was achieved in 95.1% (95% CI 92.1-97.0%) and 96.4% (95% CI 95.5-97.2%), respectively. Response rates were high regardless of treatment regimen (with or without RBV), and among patients receiving a standard or high dose of PPIs. Regarding safety, adverse events and serious adverse events were more frequently reported in patients taking concomitant ARAs, though baseline population differences may have played a role.
  
  
  
  In phase 3 trials of OBV/PTV/r plus DSV and RBV in HCV genotype 1-infected patients, SVR12 rates were high regardless of ARA/PPI use or PPI dose. These data support the co-administration of this regimen with ARAs including PPIs.
authors.affiliation: Liver Institute of Virginia, Bon Secours Health System, Newport News and Richmond, Virginia, USA.
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.affiliation: Thomas E. Starzl Transplantation Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Vinod
authors.initials: V
authors.lastname: Rustgi
authors.affiliation: Medical Associates Research Group, San Diego, California, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.affiliation: Liver Unit, Hospital Clinic, CIBERehd, IDIBAPS, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
authors.affiliation: Centre de Recherche sur l'Inflammation, Inserm UMR 1149, Université Paris Diderot, AP-HP Hôpital Beaujon, Clichy, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.affiliation: Hospital Germans TríasiPujol, CIBERehd, Badalona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Planas Vila
authors.affiliation: AbbVie Inc., North Chicago, Illinois, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: AbbVie Inc., North Chicago, Illinois, USA.
authors.forename: Marcos
authors.initials: M
authors.lastname: Pedrosa
authors.affiliation: AbbVie Inc., North Chicago, Illinois, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Moller
authors.affiliation: Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Reau
mesh_terms: D015081:2-Naphthylamine; D000813:Anilides / Q000627:therapeutic use; D000863:Antacids / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D002219:Carbamates / Q000627:therapeutic use; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007372:Interferons / Q000627:therapeutic use; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000031:analogs & derivatives; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012254:Ribavirin / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D016896:Treatment Outcome; D014498:Uracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D014633:Valine
chemical_list: D000813:Anilides; D000863:Antacids; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D054328:Proton Pump Inhibitors; D013449:Sulfonamides; C586094:ombitasvir; D012254:Ribavirin; D014498:Uracil; D007372:Interferons; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D014633:Valine; D019438:Ritonavir; C585405:paritaprevir