Prevalence of Resistance-Associated Substitutions in HCV NS5A, NS5B, or NS3 and Outcomes of Treatment With Ledipasvir and Sofosbuvir

Liang, 2013, Current and future therapies for hepatitis C virus infection, N Engl J Med, 368, 1907, 10.1056/NEJMra1213651

Afdhal, 2014, Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection, N Engl J Med, 370, 1889, 10.1056/NEJMoa1402454

Afdhal, 2014, Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection, N Engl J Med, 370, 1483, 10.1056/NEJMoa1316366

Kowdley, 2014, Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis, N Engl J Med, 370, 1879, 10.1056/NEJMoa1402355

Lawitz, 2014, Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial, Lancet, 383, 515, 10.1016/S0140-6736(13)62121-2

Lawitz, 2012, A phase 1, randomized, placebo-controlled, 3-day, dose-ranging study of GS-5885, an NS5A inhibitor, in patients with genotype 1 hepatitis C, J Hepatol, 57, 24, 10.1016/j.jhep.2011.12.029

Rong, 2010, Rapid emergence of protease inhibitor resistance in hepatitis C virus, Sci Transl Med, 2, 30ra32, 10.1126/scitranslmed.3000544

Sarrazin, 2010, Resistance to direct antiviral agents in patients with hepatitis C virus infection, Gastroenterology, 138, 447, 10.1053/j.gastro.2009.11.055

Wong, 2013, Characterization of hepatitis C virus resistance from a multiple-dose clinical trial of the novel NS5A inhibitor GS-5885, Antimicrob Agents Chemother, 57, 6333, 10.1128/AAC.02193-12

Cheng, 2016, In vitro antiviral activity and resistance profile characterization of the hepatitis C virus NS5A inhibitor ledipasvir, Antimicrob Agents Chemother, 60, 1847, 10.1128/AAC.02524-15

Lam, 2012, Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus, Antimicrob Agents Chemother, 56, 3359, 10.1128/AAC.00054-12

Dutartre, 2006, 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, 50, 4161, 10.1128/AAC.00433-06

Le Pogam, 2006, In vitro selected Con1 subgenomic replicons resistant to 2'-C-methyl-cytidine or to R1479 show lack of cross resistance, Virology, 351, 349, 10.1016/j.virol.2006.03.045

Tong, 2014, In vivo emergence of a novel mutant L159F/L320F in the NS5B polymerase confers low-level resistance to the HCV polymerase inhibitors mericitabine and sofosbuvir, J Infect Dis, 209, 668, 10.1093/infdis/jit562

Svarovskaia, 2014, Infrequent development of resistance in genotype 1-6 hepatitis C virus-infected subjects treated with sofosbuvir in phase 2 and 3 clinical trials, Clin Infect Dis, 59, 1666, 10.1093/cid/ciu697

Svarovskaia, 2016, L159F and V321A sofosbuvir-associated hepatitis C virus NS5B substitutions, J Infect Dis, 213, 1240, 10.1093/infdis/jiv564

Kwo, 2016, Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1-infected patients without cirrhosis: OPTIMIST-1, a phase 3, randomized study, Hepatology, 64, 370, 10.1002/hep.28467

Lawitz, 2016, Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A phase 3 study (OPTIMIST-2), Hepatology, 64, 360, 10.1002/hep.28422

Manns, 2014, All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study, Lancet, 384, 1597, 10.1016/S0140-6736(14)61059-X

Sulkowski, 2014, Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection, N Engl J Med, 370, 211, 10.1056/NEJMoa1306218

Gane, 2014, Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection, Gastroenterology, 146, 736, 10.1053/j.gastro.2013.11.007

2012, Clinically relevant HCV drug resistance mutations figure and tables (updated), Ann Forum Collab HIV Res, 14, 1

Shih, 2011, Mechanistic characterization of GS-9190 (tegobuvir), a novel non-nucleoside inhibitor of hepatitis C virus NS5B polymerase, Antimicrob Agents Chemother, 55, 4196, 10.1128/AAC.00307-11

Lohmann, 1999, Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line, Science, 285, 110, 10.1126/science.285.5424.110

Bartels, 2013, Hepatitis C virus variants with decreased sensitivity to direct-acting antivirals (DAAs) were rarely observed in DAA-naive patients prior to treatment, J Virol, 87, 1544, 10.1128/JVI.02294-12

Suzuki, 2012, Prevalence of hepatitis C virus variants resistant to NS3 protease inhibitors or the NS5A inhibitor (BMS-790052) in hepatitis patients with genotype 1b, J Clin Virol, 54, 352, 10.1016/j.jcv.2012.04.024

Zeuzem, 2016, Abstract 91. Prevalence of pre-treatment NS5A resistance associated variants in genotype 1 patients across different regions using deep sequencing and effect on treatment outcome with LDV/SOF, Hepatology, 62, 254A

Bourliere, 2015, Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS), Lancet Infect Dis, 15, 397, 10.1016/S1473-3099(15)70050-2

Lawitz, 2015, Retreatment of patients who failed 8 or 12 weeks of ledipasvir/sofosbuvir-based regiments with ledipasvir/sofosbuvir for 24 weeks, J Hepatol, 62, S192, 10.1016/S0168-8278(15)30012-X

Terrault N, Zeuzem S, Di Bisceglie AM, et al. Treatment outcomes with 8, 12 and 24 week regimens of ledipasvir/sofosbuvir for the treatment of hepatitis C infection: analysis of a multicenter prospective, observational study (abstr 94). Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), Boston, MA, Nov 13-17, 2015.

Afdhal NH, Bacon B, Dieterich D, et al. Su1429: Failure with all-oral DAA regimens: real-world experience from the TRIO Network (abstr LB-17). Gastroenterology 2016;150;4(Suppl 1):S1097.