Research ArticleSafety and efficacy of daclatasvir-sofosbuvir in HCV genotype 1-mono-infected patients
Graphical abstract
Introduction
The very rapidly evolving field of hepatitis C virus (HCV) therapy indicates the need for an extensive screening of HCV-infected patients and their access to antiviral treatment, due to the high rate of sustained virological response (SVR). Antiviral therapy may be considered for the treatment of any patient with chronic HCV infection, as recently recommended by the European Association for the Study of the Liver (EASL) guidelines.
Since 2011, the treatment of chronic hepatitis C has dramatically improved with the development of direct-acting antiviral (DAA) agents.
A better understanding of the viral lifecycle, and the characterization of viral enzymes, which are potential targets, has resulted in the development of new molecules, DAAs against HCV. These are either specific for genotype 1 (NS3/NS4A protease inhibitors) or cover a wider spectrum (NS5A and NS5B polymerase inhibitors or entry inhibitors), as well as non-specific antivirals [1], [2], [3], [4], [5]. The available drugs in 2016 are from a second generation of NS5B polymerase inhibitors (sofosbuvir, dasabuvir), protease inhibitors (simeprevir, paritaprevir, grazoprevir) and NS5A replication complex inhibitors (daclatasvir, then ledipasvir, ombitasvir and elbasvir) [6], [7]. They have been approved, evaluated [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], and their combination is now recommended for treating HCV chronic infection [17], [18]. Given the timelines for approval and usage beyond the results of the clinical trials, real-life results of the sofosbuvir + ribavirin [25] or sofosbuvir + simeprevir combination have been extensively reported [26], [27], [28]. However, there is little data regarding the sofosbuvir + daclatasvir combination in genotype 1-infected patients.
We report the first real-life results of the France REcherche Nord&Sud Sida-hiv Hépatites (ANRS) CO22 HEPATHER cohort (Therapeutic options for hepatitis B and C: A French cohort) for the sofosbuvir + daclatasvir combination in genotype 1-infected patients.
Section snippets
Study design and participants
The ANRS CO22 HEPATHER cohort “Therapeutic options for hepatitis B and C: a French cohort” is a national multicentre prospective observational cohort study of patients with viral hepatitis B or C (this study is registered with ClinicalTrials.gov, number: NCT01953458). The cohort was set up in August 2012 with the main objectives to quantify the clinical efficacy and safety of new hepatitis treatments in real-life, and to identify, at the patient level, who were most likely improve in overall
Results
By October 1st 2014, 768 cohort participants with a HCV genotype 1 infection had started a sofosbuvir + daclatasvir combination, of which 599 (78%) did not receive and 169 (22%) received ribavirin, according to the physician (Fig. 1). One hundred and ninety-four (25%) patients were treated for 12 weeks, and 574 (75%) were treated for 24 weeks. There was no difference according to whether the regimen contained ribavirin (p = 0.0886). The patient characteristics are described in Table 1. Patients who
Discussion
This is the first report of the real-life results of the sofosbuvir + daclatasvir combination in genotype 1-infected patients. We showed that the sofosbuvir + daclatasvir combination was associated with a high SVR12 rate and we explored the impact of treatment duration and ribavirin combination in patients infected with HCV genotype 1. Cirrhosis was strongly associated with treatment failure. Almost all non-cirrhotic patients achieved a SVR irrespective of the treatment schedule and a 12-week
Financial support
INSERM-ANRS (France REcherche Nord&sud Sida-vih Hépatites), France, ANR (Agence Nationale de la Recherche), France, DGS (Direction Générale de la Santé), France and MSD, United States, Janssen, United States, Gilead, United States, Abbvie, United States, BMS, United States, Roche, Switzerland.
Conflict of interest
Dr. Hezode reports personal fees from Abbvie, personal fees from BMS, personal fees from Gilead, personal fees from Janssen, personal fees from MSD, personal fees from Roche, outside the submitted work. Dr. Guyader reports grants and personal fees from JANSSEN, personal fees from GILEAD, personal fees from MSD, personal fees from INTERCEPT, personal fees from ABBVIE, personal fees from BMS, outside the submitted work. Dr. Samuel reports other from Astellas, other from BMS, other from Gilead,
Authors’ contributions
Dr Carrat had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Pol, Fontaine, Carrat. Acquisition of data: Pol, Bourlière, Hezode, Larrey, Bronowicki, De Ledinghen, Zoulim, Tran, Metivier, Zarski, Samuel, Guyader, Marcellin, Minello, Alric, Thabut, Chazouillères, Riachi, Bourcier, Mathurin, Loustaud-Ratti, D’Alteroche, Hubert, Habersetzer, Causse, Geist, Rosa, Gournay, Saillard,
Acknowledgements
We thank the study participants and the participating clinicians at each site.
We thank the Inserm-ANRS for sponsoring, funding and conducting the ANRS CO22 HEPATHER cohort in collaboration with Association Française pour l’Etude du Foie (AFEF). The cohort received supports from ANR (Agence Nationale de la Recherche), DGS (Direction Générale de la Santé) and MSD, Janssen, Gilead, Abbvie, BMS, Roche. Please find details of the ANRS-AFEF HEPATHER study group in the Supplementary material.
References (31)
- et al.
Sofosbuvir plus Ribavirin for treatment of hepatitis C virus in patients coinfected with HIV (PHOTON-2): a multicentre, open-label, non-randomised study
Lancet
(2015) - et al.
Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis virus infection after liver transplantation
Gastroenterology
(2015) - et al.
Sofosbuvir plus ribavirin for the treatment of chronic genotype 4 hepatitis C infection in patients of Egyptian ancestry
J Hepatol
(2015) - et al.
Sofosbuvir plus ribavirin for treating Egyptian patients with hepatitis genotype 4
J Hepatol
(2015) - et al.
Sofosbuvir and daclatasvir combination therapy in a liver transplant recipient with severe recurrent cholestatic hepatitis C
Am J Transplant
(2013) - et al.
Sofosbuvir plus daclatasvir for post-transplant recurrent hepatitis C: potent antiviral activity but no clinical benefit if treatment is given late
Dig Liv Dis
(2014) - et al.
Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomized, double-blind, phase 2 trial (SIRIUS)
Lancet Infect Dis
(2015) - et al.
Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect
Nature
(2010) - et al.
Resistance analysis of the hepatitis C virus NS5A inhibitor BS-790052 in an in vitro replicon system
Antimicrob Agents Chemother
(2010) - et al.
Discovery of a beta-d-2’-deoxy-2’-alfa-fluoro-2’-beta-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus
J Med Chem
(2010)
Assessment of pharcokinetic interactions of the HCV NS5A replication complex inhibitor daclatasvir with antiretroviral agents: ritonavir-boosted atazanavir, efavirenz and tenofovir
Antivir Ther
Effect of coadministration of daclatasvir on the pharmacokinetics of combined oral contraceptive containing ethynil estradiol and norgestimate
Antivir Ther
Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C
N Eng J Med
Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection
N Eng J Med
Sofosbuvir for previously untreated chronic hepatitis C infection
N Eng J Med
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