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Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b-infected null responders.
- Source :
-
Hepatology (Baltimore, Md.) [Hepatology] 2012 Mar; Vol. 55 (3), pp. 742-8. Date of Electronic Publication: 2012 Jan 30. - Publication Year :
- 2012
-
Abstract
- Unlabelled: Patients with chronic hepatitis C virus (HCV) infection and previous null response to pegylated interferon (Peg-IFN) and ribavirin (RBV) have limited therapeutic options. HCV genotype 1 is the most common worldwide and the most difficult to treat; genotype 1b is the most common subtype of genotype 1 outside North America. The enhanced antiviral activity achieved by combining two direct-acting antiviral (DAA) agents may improve clinical outcomes. This open-label, phase IIa study included 10 patients with chronic HCV genotype 1b infection and previous null response (<2 log(10) reduction in HCV RNA after 12 weeks) to Peg-IFN and RBV. Patients received dual DAA treatment for 24 weeks with the nonstructural protein 5A replication complex inhibitor, daclatasvir (60 mg once-daily), and the nonstructural protein 3 protease inhibitor, asunaprevir (initially 600 mg twice-daily, then subsequently reduced to 200 mg twice-daily). The primary efficacy endpoint was the proportion of patients with sustained virologic response (SVR) at 12 weeks post-treatment (SVR(12) ). Nine patients completed 24 weeks of treatment; 1 patient discontinued treatment after 2 weeks. In the 9 patients who completed the full course of treatment, HCV RNA was undetectable at week 8 and remained undetectable through the end of treatment; all 9 patients achieved SVR(12) and SVR(24) . HCV RNA also remained undetectable post-treatment in the patient who discontinued after 2 weeks. There was no viral breakthrough. Diarrhea and headache, generally mild, were the most common adverse events; transaminase elevations were reported in 3 patients, but did not result in discontinuation.<br />Conclusions: Dual therapy with daclatasvir and asunaprevir, without Peg-IFN and RBV, can achieve high SVR rates in difficult-to-treat patients with HCV genotype 1b infection and previous null response to Peg-IFN and RBV.<br /> (Copyright © 2011 American Association for the Study of Liver Diseases.)
- Subjects :
- Adult
Aged
Antiviral Agents adverse effects
Carbamates
Diarrhea chemically induced
Diarrhea epidemiology
Drug Therapy, Combination
Female
Genotype
Headache chemically induced
Headache epidemiology
Hepatitis C ethnology
Humans
Imidazoles adverse effects
Incidence
Interferon-alpha therapeutic use
Isoquinolines adverse effects
Isoquinolines therapeutic use
Japan
Male
Middle Aged
Polyethylene Glycols therapeutic use
Protease Inhibitors adverse effects
Pyrrolidines
Recombinant Proteins therapeutic use
Ribavirin therapeutic use
Sulfonamides adverse effects
Sulfonamides therapeutic use
Treatment Failure
Treatment Outcome
Valine analogs & derivatives
Antiviral Agents therapeutic use
Hepacivirus genetics
Hepatitis C drug therapy
Imidazoles therapeutic use
Protease Inhibitors therapeutic use
Viral Nonstructural Proteins antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1527-3350
- Volume :
- 55
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Hepatology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 21987462
- Full Text :
- https://doi.org/10.1002/hep.24724