Highlights
- •SOF/VEL/VOX for 12 weeks resulted in a 96% SVR12 rate in NS5A inhibitor-experienced patients.
- •SOF/VEL/VOX for 12 weeks resulted in a 98% SVR12 rate in DAA-experienced patients naïve to NS5A inhibitors.
- •83% of DAA-experienced patients had baseline NS3 and/or NS5A RASs.
- •79% of NS5A inhibitor-experienced patients had baseline NS5A RASs.
- •Baseline RASs had no impact on virologic response in DAA-experienced patients following 12 weeks SOF/VEL/VOX.
Background & Aims
Methods
Results
Conclusions
Lay summary
Graphical abstract

Keywords
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of HepatologyReferences
Author names in bold designate shared co-first authorship
- Viral hepatitis and the Global Burden of Disease: a need to regroup.J Viral Hepat. 2013; 20: 600-601
- Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence.Hepatology. 2013; 57: 1333-1342
- Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study.Lancet. 2017; 2: 161-176
- The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide.J Hepatol. 2006; 45: 529-538
- Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus.Hepatology. 2015; 62: 932-954
- The changing landscape of hepatitis C virus therapy: focus on interferon-free treatment.Therap Adv Gastroenterol. 2015; 8: 298-312
- Interferon-free combination therapies for the treatment of hepatitis C: current insights.Hepat Med. 2015; 7: 51-70
Nelson DR. HCV-TARGET International Registry Do Phase III Trials Translate into Real World [Presentation]. In: 15th International Symposium on Viral Hepatitis and Liver Disease (ISVHLD); 2015 26–28 June; Berlin, Germany; 2015.
Welzel TM, Nelson DR, Morelli G, Di Bisceglie AM, Reddy KR, Kuo A, et al. Safety and Efficacy of Sofosbuvir and Ribavirin for the Treatment of HCV Genotype 2 and 3: Results of the HCV-TARGET Study [Abstract 1057]. In: 66th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2015 13–17 November; San Francisco, CA; 2015. p. 727A–728A.
Dieterich DT, Bacon B, Curry M, Flamm SL, Guest L, Kowdley K, et al. Ledipasvir/Sofosbuvir +/- Ribavirin in Patients Co-infected with HCV and HIV: Real-World Heterogeneous Population from the TRIO Network [Poster #SAT-134]. In: European Association for the Study of the Liver (EASL); 2016 13–17 April; Barcelona, Spain; 2016.
Dieterich DT, Bacon B, Flamm SL, Kowdley K, Milligan S, Tsai N, et al. Final Evaluation of 955 HCV Patients Treated with 12 Week Regimens Containing Sofosbuvir +/- Simeprevir in the Trio Network: Academic and Community Treatment of a Real-World, Heterogeneous Population [Abstract P0775]. In: Digestive Disease Week (DDW); 2015 17–19 May; Washington, DC; 2015.
Younossi ZM, Bacon B, Dieterich DT, Flamm SL, Kowdley K, Lawitz E, et al. Evaluation of Access to Care in Patients Prescribed Sofosbuvir-Containing Regimens: Data From the TRIO Network [Abstract Tu1033]. In: Digestive Disease Week 2015 (DDW); 2015 17–19 May; Washington, DC; 2015. p. S1090.
Dieterich D, Bacon B, Flamm S, Kowley K, Milligan S, Tsai N, et al. Final evaluation of 955 HCV patients treated with 12 week regimens containing sofosbuvir +/-simeprevir in the trio network: Academic and community treatment of a real-world, heterogeneous population [Abstract P0775]. In: 50th Annual Meeting of the European Association for the Study of the Liver (EASL); 2015 22–26 April; Vienna, Austria; 2015. p. S621.
- Long-term persistence of HCV NS5A resistance associated substitutions after treatment with the HCV NS5A inhibitor, ledipasvir, without sofosbuvir.Antivir Ther. 2017;
- Persistence of resistant variants in hepatitis C virus-infected patients treated with the NS5A replication complex inhibitor daclatasvir.Antimicrob Agents Chemother. 2013; 57: 2054-2065
Lawitz E, Flamm S, Yang JC, Pang PS, Zhu Y, Svarovskaia E, et al. Retreatment of Patients Who Failed 8 or 12 Weeks of Ledipasvir/Sofosbuvir-Based Regimens With Ledipasvir/Sofosbuvir for 24 Weeks. In: European Association for the Study of the Liver (EASL). The 50th International Liver Congress; 2015 April 22–26; Vienna, Austria; 2015.
Gane EJ, Shiffman ML, Etzkorn K, Morelli G, Stedman C, Davis MN, et al. Sofosbuvir/Velpatasvir in Combination With Ribavirin for 24 Weeks Is Effective Retreatment for Patients Who Failed Prior NS5A-Containing DAA Regimens: Results of the Retreatment Study [Presentation PS-024]. In: European Association for the Study of the Liver (EASL); 2016 13–17 April; Barcelona, Spain; 2016.
- Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus.Antimicrob Agents Chemother. 2012; 56: 3359-3368
- General catalytic deficiency of hepatitis C virus RNA polymerase with an S282T mutation and mutually exclusive resistance towards 2'-modified nucleotide analogues.Antimicrob Agents Chemother. 2006; 50: 4161-4169
- Infrequent development of resistance in genotype 1–6 hepatitis C virus-infected subjects treated with sofosbuvir in phase II and 3 clinical trials.Clin Infect Dis. 2014; 59: 1666-1674
- Clinical resistance to velpatasvir (GS-5816), a Novel pan-genotypic inhibitor of the hepatitis C virus NS5A protein.Antimicrob Agents Chemother. 2016; 60: 5368-5378
- In vitro resistance profile of the hepatitis C virus NS3/4A protease inhibitor TMC435.Antimicrob Agents Chemother. 2010; 54: 1878-1887
- Resistance analysis of the hepatitis C virus NS3 protease inhibitor asunaprevir.Antimicrob Agents Chemother. 2012; 56: 3670-3681
- In vitro and in vivo antiviral activity and resistance profile of the hepatitis C virus NS3/4A protease inhibitor ABT-450.Antimicrob Agents Chemother. 2015; 59: 988-997
- The molecular basis of drug resistance against hepatitis C virus NS3/4A protease inhibitors.PLoS Pathog. 2012; 8: e1002832
- MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants.Antimicrob Agents Chemother. 2012; 56: 4161-4167
Taylor JG, Appleby T, Barauskas O, Chen X, Dvory-Sobol H, Gong R, et al. Preclinical Profile of the Pangenotypic HCV NS3/4A Protease Inhibitor GS-9857 [Poster P0899]. In: European Association for the Study of the Liver (EASL). 50th International Liver Congress.; 2015 22–26 April; Vienna, Austria; 2015.
Lawitz E, Dvory-Sobol H, Yang JC, Stamm LM, Taylor JG, Brainard DM, et al. Characterization of HCV Resistance From a 3-Day Monotherapy Study of GS-9857, a Novel Pangenotypic NS3/4A Protease Inhibitor [Poster 718]. In: American Association for the Study of Liver Diseases (AASLD); 2015 13–17 November; San Francisco, CA; 2015.
- Vaniprevir with pegylated interferon alpha-2a and ribavirin in treatment-naive patients with chronic hepatitis C: a randomized phase II study.Hepatology. 2012; 56: 884-893
- Molecular modeling study on the resistance mechanism of HCV NS3/4A serine protease mutants R155K, A156V and D168A to TMC435.Antiviral Res. 2012; 93: 126-137
- Understanding the drug resistance mechanism of hepatitis C virus NS3/4A to ITMN-191 due to R155K, A156V, D168A/E mutations: a computational study.Biochim Biophys Acta. 2012; 1820: 1526-1534
- Patterns of resistance-associated substitutions in patients with chronic HCV infection following treatment with direct-acting antivirals.Gastroenterology. 2018; 154: e974
- Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection.N Engl J Med. 2017; : 2134-2146
VOSEVI™, Gilead Sciences Incorporated. VOSEVI™ (sofosbuvir, velpatasvir, and voxilaprevir) tablets, for oral use. US Prescribing Information. Foster City, CA Revised: July. In; 2017.
VOSEVI™, Gilead Sciences Ireland UC. VOSEVI™ 400 mg/100 mg/100 mg film-coated tablets sofosbuvir/velpatasvir/voxilaprevir. Summary of Product Characteristics (SmPC). County Cork, Ireland. Revised: July. In; 2017.
- Virus resistance to direct-acting antiviral drugs in interferon-free regimens.Gastroenterology. 2016; 151: 70-86
- US FDA perspective on elbasvir/grazoprevir treatment for patients with chronic hepatitis C virus genotype 1 or 4 infection.Clin Drug Investig. 2017; 37: 317-326
- Regulatory analysis of effects of hepatitis C virus NS5A polymorphisms on efficacy of elbasvir and grazoprevir.Gastroenterology. 2017; 152: 586-597
- Mechanistic characterization of GS-9190 (tegobuvir), a novel non-nucleoside inhibitor of hepatitis C virus NS5B polymerase.Antimicrob Agents Chemother. 2011; 55: 4196-4203
- Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line.Science. 1999; 285: 110-113
- Characterization of resistance to the protease inhibitor GS-9451 in hepatitis C virus-infected patients.Antimicrob Agents Chemother. 2012; 56: 5289-5295
- Evolution of treatment-emergent resistant variants in telaprevir phase III clinical trials.Clin Infect Dis. 2013; 57: 221-229
- Long-term follow-up of patients receiving boceprevir for treatment of chronic hepatitis C.Antiviral Res. 2015; 113: 71-78
- Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in Phase IIb/III studies.J Hepatol. 2015; 62: 1008-1014
- Grazoprevir, elbasvir, and ribavirin for chronic hepatitis C virus genotype 1 infection after failure of pegylated interferon and ribavirin with an earlier-generation protease inhibitor: final 24-week results from C-SALVAGE.Clin Infect Dis. 2016; 62: 32-36
Roberts SK, Cooper CL, Lawitz E, Reddy KR, Thompson AJ, Zeuzem S, et al. SOF/VEL/VOX Results in High SVR12 Rates When Administered for 12 Weeks in DAA-Experienced Patients or for 8 Weeks in DAA-Naïve Patients: an Integrated Analysis of the POLARIS-1, POLARIS-2, POLARIS-3, and POLARIS-4 Studies [Poster SAT-280]. In: The International Liver Congress™ 2017: European Association for the Study of the Liver (EASL); 2017 19–23 April; Amsterdam, the Netherlands; 2017.
- Sofosbuvir/velpatasvir in combination with ribavirin for 24 weeks is effective retreatment for patients who failed prior NS5A containing DAA regimens: results of the GS-US-342-1553 study [Abstract PS024].J Hepatol. 2016; 64: S147-S148
Poordad P, Pol S, Asatryan A, Buti M, Shaw D, Hézode C, et al. MAGELLAN-1, Part 2: glecaprevir and pibrentasvir for 12 or 16 weeks in patients with chronic hepatitis C virus genotype 1 or 4 and prior direct-acting antiviral treatment failure [Presentation]. In: The International Liver Congress™ 2017: European Association for the Study of the Liver (EASL); 2017 19–23 April; Amsterdam, the Netherlands 2017.
Pilot-Matias T, Krishnan R, Schnell G, Tripathi R, Beyer J, Reisch T, et al. Resistance Analysis in the MAGELLAN-1 Study (Part 2): Glecaprevir/Pibrentasvir Therapy in HCV-Infected Patients Who Had Failed Prior DAA Regimens Containing NS3/4A Protease and/or NS5A Inhibitors [Presentation SAT-204]. In: The International Liver Congress™ 2017: European Association for the Study of the Liver (EASL); 2017 19–23 April; Amsterdam, the Netherlands; 2017.