Effects of 12-week treatment with Sovodak in patients infected by genotype 1 hepatitis C virus

Introduction: It has been shown that the combination therapy of Sofosbuvir-Daclatasvir (Sof/Dac) has a high rate of success in the treatment of patients. For the first time, a single pill of Sof/Dac has been formulated in Iran (Sovodak). In this regard, the present study was carried out aiming to investigate the safety and efficacy of Sovodak for 12 weeks during treatment of patients infected by genotype 1 hepatitis C virus (HCV). Methods: In this study, 50 patients (25 and 25 treatment-naïve and treatment-experienced patients, respectively) infected by HCV genotype 1 received Sovodak (1pill per day) for 12 weeks. Ribavirin was added for patients who had definitive evidence of liver cirrhosis. The sustained virological response (SVR12) was investigated 12 weeks after the end of the therapy. Results: All 50 patients completed the treatment period. The mean age of patients was 54.40 ± 11.69 years, in addition, 60% and 90% of the patients were male and infected by HCV genotype 1b, respectively. After 4 and 12 weeks of treatment with Sovodak, the HCV ribonucleic acid (RNA) titer was undetectable in 82% and 100 % of the patients, respectively and 100% of them achieved SVR12. None of the subjects reported treatment discontinuation because of adverse events, however, 3 patients reported transient side effects including foot swelling, headache, and vomiting. Conclusion: The results of this study showed that once-daily Sovodak single-pill for 12 weeks is an effective and safe medicine for treating patients infected by HCV genotype 1

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In VitroActivity and Resistance Profile of Dasabuvir, a Nonnucleoside Hepatitis C Virus Polymerase Inhibitor

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04619-14 ◽

2014 ◽

Vol 59 (3) ◽

pp. 1505-1511 ◽

Cited By ~ 73

Author(s):

Warren Kati ◽

Gennadiy Koev ◽

Michelle Irvin ◽

Jill Beyer ◽

Yaya Liu ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Clinical Isolates ◽

Genotype 1 ◽

Subgenomic Replicon ◽

Hcv Genotype ◽

Genotype 1A ◽

Treatment Naïve ◽

Hcv Genotype 1 ◽

Hcv Ns5b

ABSTRACTDasabuvir (ABT-333) is a nonnucleoside inhibitor of the RNA-dependent RNA polymerase encoded by the hepatitis C virus (HCV) NS5B gene. Dasabuvir inhibited recombinant NS5B polymerases derived from HCV genotype 1a and 1b clinical isolates, with 50% inhibitory concentration (IC50) values between 2.2 and 10.7 nM, and was at least 7,000-fold selective for the inhibition of HCV genotype 1 polymerases over human/mammalian polymerases. In the HCV subgenomic replicon system, dasabuvir inhibited genotype 1a (strain H77) and 1b (strain Con1) replicons with 50% effective concentration (EC50) values of 7.7 and 1.8 nM, respectively, with a 13-fold decrease in inhibitory activity in the presence of 40% human plasma. This level of activity was retained against a panel of chimeric subgenomic replicons that contained HCV NS5B genes from 22 genotype 1 clinical isolates from treatment-naive patients, with EC50s ranging between 0.15 and 8.57 nM. Maintenance of replicon-containing cells in medium containing dasabuvir at concentrations 10-fold or 100-fold greater than the EC50resulted in selection of resistant replicon clones. Sequencing of the NS5B coding regions from these clones revealed the presence of variants, including C316Y, M414T, Y448C, Y448H, and S556G, that are consistent with binding to the palm I site of HCV polymerase. Consequently, dasabuvir retained full activity against replicons known to confer resistance to other polymerase inhibitors, including the S282T variant in the nucleoside binding site and the M423T, P495A, P495S, and V499A single variants in the thumb domain. The use of dasabuvir in combination with inhibitors targeting HCV NS3/NS4A protease (ABT-450 with ritonavir) and NS5A (ombitasvir) is in development for the treatment of HCV genotype 1 infections.

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Faculty Opinions recommendation of An Open-Label Trial of 12-Week Simeprevir plus Peginterferon/Ribavirin (PR) in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 1 (GT1).

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726542168.793521378 ◽

2016 ◽

Author(s):

Philip Rosenthal

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Genotype 1 ◽

Open Label ◽

Hcv Genotype ◽

Treatment Naïve ◽

Open Label Trial ◽

Hcv Genotype 1

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An Open-Label Trial of 12-Week Simeprevir plus Peginterferon/Ribavirin (PR) in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 1 (GT1)

PLoS ONE ◽

10.1371/journal.pone.0158526 ◽

2016 ◽

Vol 11 (7) ◽

pp. e0158526 ◽

Cited By ~ 2

Author(s):

Tarik Asselah ◽

Christophe Moreno ◽

Christoph Sarrazin ◽

Michael Gschwantler ◽

Graham R. Foster ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Genotype 1 ◽

Open Label ◽

Hcv Genotype ◽

Treatment Naïve ◽

Open Label Trial ◽

Hcv Genotype 1

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Grazoprevir and Elbasvir in Patients with Genotype 1 Hepatitis C Virus Infection: A Comprehensive Efficacy and Safety Analysis

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2017/8186275 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Yinan Yao ◽

Ming Yue ◽

Jie Wang ◽

Hongbo Chen ◽

Mei Liu ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Efficacy And Safety ◽

Genotype 1 ◽

Hcv Genotype ◽

Link Type ◽

End Of Treatment ◽

Treatment Naïve ◽

Previously Treated Patients ◽

Hcv Genotype 1

Background. It is urgent for patients with hepatitis C virus (HCV) infection to find a safe, effective, and interferon-free regimen to optimize therapy. A comprehensive analysis was performed to evaluate the efficacy and safety of the grazoprevir combined with elbasvir, with or without ribavirin (RBV), in 777 treatment-naive and treatment-experienced patients with HCV genotype 1 infection from 3 randomized controlled trials (RCTs). Method. We collected data from the following trials: C-WORTHY (NCT01717326), C-SALVAGE (NCT02105454), and C-EDGE (NCT02105467). All patients received grazoprevir plus elbasvir with or without RBV for 12 or 18 weeks. The sustained virological response (SVR) 12 weeks after end of treatment was calculated for overall and subgroups. Results. 568 (73%) patients were treatment-naive. Overall, 95% (95% CI: 93–96) patients achieved SVR12, 95% (95% CI: 92–96) for treatment-naive and 96% (95% CI: 92–98) for previously treated patients, respectively. Treatment duration and treatment regimen did not have great difference in SVR12 rates. The most common AEs were fatigue (18%–29%), headache (20%), nausea (8%–14%), and asthenia (4%–12%). One patient (<1%) receiving grazoprevir plus elbasvir alone and one (<1%) receiving grazoprevir plus elbasvir plus RBV had treatment-related serious AEs. Conclusions. The result shows that 12-week grazoprevir plus elbasvir therapy is safe and effective for treatment-naive patients with HCV genotype 1.

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