title: Ombitasvir/paritaprevir/r and dasabuvir plus ribavirin in HCV genotype 1-infected patients on methadone or buprenorphine.
abstract: OBJECTIVE
  Hepatitis C virus (HCV)-infected patients with a history of injection drug use have low rates of initiation and completion of interferon-based therapies. This study evaluated efficacy, safety, and pharmacokinetics of a 12-week all-oral regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir+ribavirin in HCV genotype 1-infected patients on stable opioid replacement therapy.
  
  
  METHODS
  This was a phase II, multicenter, open-label, single-arm study in treatment-naïve or peginterferon/ribavirin treatment-experienced HCV genotype 1-infected patients on methadone or buprenorphine±naloxone. Patients received 12weeks of co-formulated ombitasvir/paritaprevir/ritonavir (25mg/150mg/100mg once daily) and dasabuvir (250mg twice daily)+weight-based ribavirin. The primary efficacy endpoint was sustained virologic response 12 weeks post-treatment.
  
  
  RESULTS
  Thirty-eight non-cirrhotic patients on chronic methadone (n=19) or buprenorphine (n=19) were enrolled. A total of 37 patients (97.4%) had a sustained virologic response 12 weeks post-treatment. No patient had a viral breakthrough or relapse. One patient discontinued due to serious adverse events unrelated to study drug (cerebrovascular accident and sarcoma). The most frequent adverse events were nausea, fatigue, and headache. Eight patients had on-treatment hemoglobin concentrations <10g/dl. Pharmacokinetic analyses indicated no clinically meaningful impact of methadone or buprenorphine on ombitasvir, paritaprevir, ritonavir, dasabuvir, or dasabuvir M1 metabolite exposures. No dose adjustments of methadone or buprenorphine were required.
  
  
  CONCLUSIONS
  The interferon-free regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir+ribavirin for 12weeks was well tolerated and achieved sustained virologic response in 97.4% of patients on opioid substitution therapy in this study. This all-oral regimen may provide an effective alternative to interferon-based therapies for HCV-infected patients with a history of injection drug use.
authors.affiliation: Quest Clinical Research, San Francisco, CA, United States. Electronic address: drjay@questclinical.com.
authors.forename: Jacob
authors.initials: J
authors.lastname: Lalezari
authors.affiliation: Parkway Medical Center, Birmingham, AL, United States.
authors.forename: J Greg
authors.initials: JG
authors.lastname: Sullivan
authors.affiliation: Premier Medical Group of the Hudson Valley, PC, Poughkeepsie, NY, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Varunok
authors.affiliation: Northwest Gastroenterology Clinic, Portland, OR, United States.
authors.forename: Edward
authors.initials: E
authors.lastname: Galen
authors.affiliation: Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, United States.
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
authors.affiliation: Thomas E. Starzl Transplantation Institute, UPMC Montefiore, Pittsburgh, PA, United States.
authors.forename: Vinod
authors.initials: V
authors.lastname: Rustgi
authors.affiliation: Louisiana Research Center, LLC, Shreveport, LA, United States.
authors.forename: Humberto
authors.initials: H
authors.lastname: Aguilar
authors.affiliation: Private Practice, Bakersfield, CA, United States.
authors.forename: Franco
authors.initials: F
authors.lastname: Felizarta
authors.affiliation: AbbVie Inc., North Chicago, IL, United States.
authors.forename: Barbara
authors.initials: B
authors.lastname: McGovern
authors.affiliation: AbbVie Inc., North Chicago, IL, United States.
authors.forename: Martin
authors.initials: M
authors.lastname: King
authors.affiliation: AbbVie Inc., North Chicago, IL, United States.
authors.forename: Akshanth R
authors.initials: AR
authors.lastname: Polepally
authors.affiliation: AbbVie Inc., North Chicago, IL, United States.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Cohen
mesh_terms: D015081:2-Naphthylamine; D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects; D000813:Anilides / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000008:administration & dosage; D002047:Buprenorphine / Q000009:adverse effects*; D002219:Carbamates / Q000008:administration & dosage*; D003521:Cyclopropanes; D004279:DNA, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000008:administration & dosage*; D008297:Male; D008691:Methadone / Q000009:adverse effects*; D008875:Middle Aged; D009293:Opioid-Related Disorders; D011392:Proline / Q000031:analogs & derivatives; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014633:Valine; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D000813:Anilides; D000998:Antiviral Agents; D002219:Carbamates; D003521:Cyclopropanes; D004279:DNA, Viral; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C586094:ombitasvir; D002047:Buprenorphine; D012254:Ribavirin; D014498:Uracil; D011392:Proline; D015081:2-Naphthylamine; C588260:dasabuvir; D014633:Valine; C585405:paritaprevir; D008691:Methadone
keywords: Hepatitis C virus; Interferon-free therapy; Opioid replacement therapy; People who inject drugs; Sustained virologic response