Gastroenterology. 2013 Nov 18. pii: S0016-5085(13)01653-3. doi: 10.1053/j.gastro.2013.11.007. [Epub ahead of print]
New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand. Electronic address: firstname.lastname@example.org.
BACKGROUND & AIMS: We evaluated an all-oral regimen comprising the nucleotide polymerase inhibitor sofosbuvir with the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 in patients with genotype 1 hepatitis C virus (HCV) infection.
METHODS: A total of 113 patients were enrolled. Sofosbuvir (400 mg once daily) and ledipasvir (90 mg once daily) plus ribavirin were given for 12 weeks to treatment-naïve patients (n=25) and those who did not respond to previous therapy (prior null responders, n=9). Sofosbuvir and GS-9669 (500 mg once daily) plus ribavirin were given for 12 weeks to treatment-naïve patients (n=25) and prior null responders (n=10). Additionally, prior null responders with cirrhosis were randomly assigned to groups given a fixed-dose combination of sofosbuvir and ledipasvir, with ribavirin (n=9) or without ribavirin (n=10). Finally, a group of treatment-naïve patients received sofosbuvir, ledipasvir, and ribavirin for 6 weeks (n=25). The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12).
RESULTS: SVR12 was achieved by 25/25 (100%) of treatment-naïve patients receiving sofosbuvir, ledipasvir, and ribavirin and 23/25 (92%) of those receiving sofosbuvir, GS-9669, and ribavirin. Of treatment-naïve patients receiving 6 weeks of sofosbuvir, ledipasvir, and ribavirin, 17/25 (68%) achieved SVR12. All non-cirrhotic prior null responders receiving 12 weeks of sofosbuvir along with another direct-acting antiviral agent plus ribavirin achieved SVR12-9/9 (100%) of those receiving sofosbuvir, ledipasvir, and ribavirin and 10/10 (100%) of those receiving sofosbuvir, GS-9669, and ribavirin. Among cirrhotic prior null responders, SVR12 was achieved by 9 (100%) of those receiving sofosbuvir, ledipasvir, and ribavirin and 7 (70%) of those receiving sofosbuvir and ledipasvir without ribavirin. The most common reported adverse events were headache, fatigue, and nausea.
CONCLUSIONS: The combination of sofosbuvir and a second direct-acting antiviral agent is highly effective in treatment-naïve patients with HCV genotype 1 infection and in patients that did not respond to previous treatment.
Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
KEYWORDS: DAA, HCV, LDV, RBV, SOF, SVR12, TN, clinical trial, drug, hepatitis C virus, ledipasvir, liver cirrhosis, ribavirin, sofosbuvir, sustained virologic response 12 weeks post therapy, treatment-naïve
PMID: 24262278 [PubMed - as supplied by publisher]