Ombitasvir/paritaprevir/r and dasabuvir plus ribavirin in HCV genotype 1-infected patients on methadone or buprenorphine.
BACKGROUND & AIMS
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.
['Lalezari|Jacob|J|', 'Sullivan|J Greg|JG|', 'Varunok|Peter|P|', 'Galen|Edward|E|', 'Kowdley|Kris V|KV|', 'Rustgi|Vinod|V|', 'Aguilar|Humberto|H|', 'Felizarta|Franco|F|', 'McGovern|Barbara|B|', 'King|Martin|M|', 'Polepally|Akshanth R|AR|', 'Cohen|Daniel E|DE|']
D015081:2-Naphthylamine D000293:Adolescent D000328:Adult D000368:Aged D000701:Analgesics, Opioid D000813:Anilides D000998:Antiviral Agents D002047:Buprenorphine D002219:Carbamates D003521:Cyclopropanes D004279:DNA, Viral D004359:Drug Therapy, Combination D005260:Female D005500:Follow-Up Studies D005838:Genotype D016174:Hepacivirus D019698:Hepatitis C, Chronic D006801:Humans D047029:Lactams, Macrocyclic D047028:Macrocyclic Compounds D008297:Male D008691:Methadone D008875:Middle Aged D009293:Opioid-Related Disorders D011392:Proline D012189:Retrospective Studies D012254:Ribavirin D013449:Sulfonamides D014498:Uracil D014633:Valine D055815:Young Adult
Hepatitis C virus Opioid replacement therapy Sustained virologic response Interferon-free therapy People who inject drugs