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Efficacy of Glecaprevir and Pibrentasvir in Patients With Genotype 1 Hepatitis C Virus Infection With Treatment Failure After NS5A Inhibitor Plus Sofosbuvir Therapy
- Source :
- Gastroenterology. 157:1506-1517.e1
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Background & Aims Treatment options are limited for patients with hepatitis C (HCV) infection with treatment failure after sofosbuvir plus an NS5A inhibitor. There are some data for the efficacy of glecaprevir/pibrentasvir (G/P) in these patients. We performed a randomized trial of the safety and efficacy of 12 and 16 weeks of G/P, with or without ribavirin, in patients with HCV genotype 1 infection with treatment failure after sofosbuvir and an NS5A inhibitor. Methods We performed a phase 3b, open-label study of patients with chronic HCV genotype 1 infection who received previous treatment with sofosbuvir plus an NS5A inhibitor. Patients without cirrhosis were randomly assigned to groups that received G/P for 12 weeks (n = 78, group A) or 16 weeks (n = 49, group B). Patients with compensated cirrhosis were randomly assigned to groups that received G/P and ribavirin for 12 weeks (n = 21, group C) or G/P for 16 weeks (n = 29, group D). The primary end point was a sustained virologic response 12 weeks after treatment. Samples collected at baseline and at time of treatment failure were sequenced for resistance-associated substitutions in NS3 and NS5A. Results Of the 177 patients in the 4 groups, 81% were men, 79% had HCV genotype 1a infection, and 44% were black. Proportions of patients with sustained virologic response 12 weeks after treatment in groups A, B, C, and D were 90%, 94%, 86%, and 97%, respectively. The treatment failed in 13 (7.3%) patients with HCV genotype 1a infection, 6 (7.9%) in group A, 3 (6.1%) in group B, 3 (6.1%) in group C (6.1%), and 1 (3.4%) in group D. Most patients had baseline resistance-associated substitutions in NS5A. Treatment-emergent resistance-associated substitutions in NS3 and NS5A were observed in 9 and 10 patients with treatment failure, respectively. G/P was well tolerated. Ribavirin increased adverse events but did not increase efficacy. Conclusions In a randomized study of patients with chronic HCV genotype 1 infection who received previous treatment with sofosbuvir plus an NS5A inhibitor, 16 weeks treatment with G/P produced sustained virologic response 12 weeks after treatment in >90% of patients, including those with compensated cirrhosis. ClinicalTrials.gov , Number: NCT03092375 .
- Subjects :
- Male
0301 basic medicine
Pyrrolidines
Sustained Virologic Response
Sofosbuvir
Hepacivirus
Viral Nonstructural Proteins
medicine.disease_cause
Gastroenterology
law.invention
chemistry.chemical_compound
0302 clinical medicine
Randomized controlled trial
law
Medicine
Treatment Failure
Aged, 80 and over
Sulfonamides
virus diseases
Hepatitis C
Middle Aged
Pibrentasvir
Drug Combinations
Hepatocellular carcinoma
Drug Therapy, Combination
Female
030211 gastroenterology & hepatology
medicine.drug
Adult
medicine.medical_specialty
Genotype
Hepatitis C virus
Antiviral Agents
03 medical and health sciences
Drug Resistance, Multiple, Viral
Quinoxalines
Internal medicine
Ribavirin
Humans
Aged
Hepatology
business.industry
Glecaprevir
Hepatitis C, Chronic
medicine.disease
digestive system diseases
030104 developmental biology
chemistry
Benzimidazoles
business
Subjects
Details
- ISSN :
- 00165085
- Volume :
- 157
- Database :
- OpenAIRE
- Journal :
- Gastroenterology
- Accession number :
- edsair.doi.dedup.....d8842c85f82ef84ca35e67ee3c1e94c9