The Role of RASs /RVs in the Current Management of HCV
Abstract
:1. Introduction—Basic Concepts
2. HCV Resistance to DAAs
3. NS3-4A Protease Inhibitors
3.1. Simeprevir, SIM
3.2. Asunaprevir, ASV
3.3. Grazoprevir, GZR
3.4. Paritaprevir/r, PTV
3.5. Voxilaprevir, VOX
3.6. Glecaprevir, GLE
4. NS5A Inhibitors
4.1. Daclatasvir, DCV
4.2. Elbasvir, EBR
4.3. Ledipasvir, LDV
4.4. Ombitasvir, OMB
4.5. Pibrentasvir, PIB
4.6. Velpatasvir, VEL
5. NS5B Polymerase Inhibitors
5.1. Sofosbuvir, SOF
5.2. Dasabuvir, DSV
6. Patterns of RASs and Retreatment Options
7. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Bukh, J. The history of hepatitis C virus (HCV): Basic research reveals unique features in phylogeny, evolution and the viral life cycle with new perspectives for epidemic control. J. Hepatol. 2016, 65, S2–S21. [Google Scholar] [CrossRef] [Green Version]
- Domingo, E.; Sheldon, J.; Perales, C. Viral quasispecies evolution. Microbiol. Mol. Biol. Rev. 2012, 76, 159–216. [Google Scholar] [CrossRef] [Green Version]
- Andino, R.; Domingo, E. Viral quasispecies. Virology 2015, 479–480, 46–51. [Google Scholar] [CrossRef] [Green Version]
- Gregori, J.; Perales, C.; Rodriguez-Frias, F.; Esteban, J.I.; Quer, J.; Domingo, E. Viral quasispecies complexity measures. Virology 2016, 493, 227–237. [Google Scholar] [CrossRef]
- Farci, P.; Wollenberg, K.; Diaz, G.; Engle, R.E.; Lai, M.E.; Klenerman, P.; Purcell, R.H.; Pybus, O.G.; Alter, H.J. Profibrogenic chemokines and viral evolution predict rapid progression of hepatitis C to cirrhosis. Proc. Natl. Acad. Sci. USA 2012, 109, 14562–14567. [Google Scholar] [CrossRef] [Green Version]
- Franco, S.; Parera, M.; Aparicio, E.; Clotet, B.; Martinez, M.A. Genetic and catalytic efficiency structure of an HCV protease quasispecies. Hepatology 2007, 45, 899–910. [Google Scholar] [CrossRef]
- Hedskog, C.; Parhy, B.; Chang, S.; Zeuzem, S.; Moreno, C.; Shafran, S.D.; Borgia, S.M.; Asselah, T.; Alric, L.; Abergel, A.; et al. Identification of 19 Novel Hepatitis C Virus Subtypes-Further Expanding HCV Classification. Open Forum Infect. Dis. 2019, 6, ofz076. [Google Scholar] [CrossRef] [PubMed]
- Perales, C.; Beach, N.M.; Gallego, I.; Soria, M.E.; Quer, J.; Esteban, J.I.; Rice, C.; Domingo, E.; Sheldon, J. Response of hepatitis C virus to long-term passage in the presence of alpha interferon: Multiple mutations and a common phenotype. J. Virol. 2013, 87, 7593–7607. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sheldon, J.; Beach, N.M.; Moreno, E.; Gallego, I.; Piñeiro, D.; Martínez-Salas, E.; Gregori, J.; Quer, J.; Esteban, J.I.; Rice, C.M.; et al. Increased replicative fitness can lead to decreased drug sensitivity of hepatitis C virus. J. Virol. 2014, 88, 12098–12111. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Strahotin, C.S.; Babich, M. Hepatitis C variability, patterns of resistance, and impact on therapy. Adv. Virol. 2012, 2012, 267483. [Google Scholar] [CrossRef] [Green Version]
- Chen, Z.W.; Pang, X.C.; Li, Z.; Ren, H.; Hu, P. Pegylated-interferon plus ribavirin treatment does not alter the prevalence of resistance-associated substitutions to direct-acting antivirals in HCV genotype 1a patients. Infect. Drug Resist. 2017, 10, 275–281. [Google Scholar] [CrossRef] [Green Version]
- Pawlotsky, J.-M.; Negro, F.; Aghemo, A.; Berenguer, M.; Dalgard, O.; Dusheiko, G.; Marra, F.; Puoti, M.; Wedemeyer, H. EASL recommendations on treatment of hepatitis C: Final update of the series☆. J. Hepatol. 2020, 73, 1170–1218. [Google Scholar] [CrossRef] [PubMed]
- Pawlotsky, J.M. Retreatment of Hepatitis C Virus-Infected Patients with Direct-Acting Antiviral Failures. Semin. Liver Dis. 2019, 39, 354–368. [Google Scholar] [CrossRef] [PubMed]
- Kalaghatgi, P.; Sikorski, A.M.; Knops, E.; Rupp, D.; Sierra, S.; Heger, E.; Neumann-Fraune, M.; Beggel, B.; Walker, A.; Timm, J.; et al. Geno2pheno[HCV]—A Web-based Interpretation System to Support Hepatitis C Treatment Decisions in the Era of Direct-Acting Antiviral Agents. PLoS ONE 2016, 11, e0155869. [Google Scholar] [CrossRef]
- Pawlotsky, J.M. Hepatitis C Virus Resistance to Direct-Acting Antiviral Drugs in Interferon-Free Regimens. Gastroenterology 2016, 151, 70–86. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- AASLD-IDSA HCV Guidance Panel. Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clin. Infect. Dis. 2018, 67, 1477–1492. [Google Scholar] [CrossRef] [Green Version]
- European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2018. J. Hepatol. 2018, 69, 461–511. [Google Scholar] [CrossRef] [Green Version]
- Dietz, J.; Susser, S.; Vermehren, J.; Peiffer, K.H.; Grammatikos, G.; Berger, A.; Ferenci, P.; Buti, M.; Müllhaupt, B.; Hunyady, B.; et al. Patterns of Resistance-Associated Substitutions in Patients With Chronic HCV Infection Following Treatment With Direct-Acting Antivirals. Gastroenterology 2018, 154, 976–988.e4. [Google Scholar] [CrossRef] [Green Version]
- Baumert, T.F.; Berg, T.; Lim, J.K.; Nelson, D.R. Status of Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection and Remaining Challenges. Gastroenterology 2019, 156, 431–445. [Google Scholar] [CrossRef]
- Zeuzem, S.; Mizokami, M.; Pianko, S.; Mangia, A.; Han, K.H.; Martin, R.; Svarovskaia, E.; Dvory-Sobol, H.; Doehle, B.; Hedskog, C.; et al. NS5A resistance-associated substitutions in patients with genotype 1 hepatitis C virus: Prevalence and effect on treatment outcome. J. Hepatol. 2017, 66, 910–918. [Google Scholar] [CrossRef] [Green Version]
- Gane, E.J.; Metivier, S.; Nahass, R.; Ryan, M.; Stedman, C.A.; Svarovskaia, E.S.; Mo, H.; Doehle, B.; Dvory-Sobol, H.; Hedskog, C.; et al. The emergence of NS5B resistance associated substitution S282T after sofosbuvir-based treatment. Hepatol. Commun. 2017, 1, 538–549. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Soria, M.E.; García-Crespo, C.; Martínez-González, B.; Vázquez-Sirvent, L.; Lobo-Vega, R.; de Ávila, A.I.; Gallego, I.; Chen, Q.; García-Cehic, D.; Llorens-Revull, M.; et al. Amino Acid Substitutions Associated with Treatment Failure for Hepatitis C Virus Infection. J. Clin. Microbiol. 2020, 58. [Google Scholar] [CrossRef] [PubMed]
- Perales, C.; Chen, Q.; Soria, M.E.; Gregori, J.; Garcia-Cehic, D.; Nieto-Aponte, L.; Castells, L.; Imaz, A.; Llorens-Revull, M.; Domingo, E.; et al. Baseline hepatitis C virus resistance-associated substitutions present at frequencies lower than 15% may be clinically significant. Infect. Drug Resist. 2018, 11, 2207–2210. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bartlett, S.R.; Grebely, J.; Eltahla, A.A.; Reeves, J.D.; Howe, A.Y.M.; Miller, V.; Ceccherini-Silberstein, F.; Bull, R.A.; Douglas, M.W.; Dore, G.J.; et al. Sequencing of hepatitis C virus for detection of resistance to direct-acting antiviral therapy: A systematic review. Hepatol. Commun. 2017, 1, 379. [Google Scholar] [CrossRef] [Green Version]
- Bartenschlager, R.; Lohmann, V.; Penin, F. The molecular and structural basis of advanced antiviral therapy for hepatitis C virus infection. Nat. Rev. Microbiol. 2013, 11, 482–496. [Google Scholar] [CrossRef] [Green Version]
- Cento, V.; Mirabelli, C.; Salpini, R.; Dimonte, S.; Artese, A.; Costa, G.; Mercurio, F.; Svicher, V.; Parrotta, L.; Bertoli, A.; et al. HCV genotypes are differently prone to the development of resistance to linear and macrocyclic protease inhibitors. PLoS ONE 2012, 7, e39652. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Di Maio, V.C.; Barbaliscia, S.; Teti, E.; Fiorentino, G.; Milana, M.; Paolucci, S.; Pollicino, T.; Morsica, G.; Starace, M.; Bruzzone, B.; et al. Resistance analysis and treatment outcomes in hepatitis C virus genotype 3-infected patients within the Italian network VIRONET-C. Liver Int. 2021, 41, 1802–1814. [Google Scholar] [CrossRef]
- Sorbo, M.C.; Cento, V.; Di Maio, V.C.; Howe, A.Y.M.; Garcia, F.; Perno, C.F.; Ceccherini-Silberstein, F. Hepatitis C virus drug resistance associated substitutions and their clinical relevance: Update 2018. Drug Resist. Updates 2018, 37, 17–39. [Google Scholar] [CrossRef]
- Soumana, D.I.; Kurt Yilmaz, N.; Ali, A.; Prachanronarong, K.L.; Schiffer, C.A. Molecular and Dynamic Mechanism Underlying Drug Resistance in Genotype 3 Hepatitis C NS3/4A Protease. J. Am. Chem. Soc. 2016, 138, 11850–11859. [Google Scholar] [CrossRef] [Green Version]
- Li, G.; De Clercq, E. Current therapy for chronic hepatitis C: The role of direct-acting antivirals. Antiviral. Res. 2017, 142, 83–122. [Google Scholar] [CrossRef]
- Ng, T.; Pilot-Matias, T.; Tripathi, R. Analysis of HCV variants in the MAGELLAN-I study (Part 1): ABT-493 and ABT-530 combination therapy of genotype 1-infected patients who had failed prior direct acting antiviral-containing regimens. Hepatology 2016, 64, P849. [Google Scholar]
- Sarrazin, C. The importance of resistance to direct antiviral drugs in HCV infection in clinical practice. J. Hepatol. 2016, 64, 486–504. [Google Scholar] [CrossRef] [PubMed]
- Lenz, O.; Verbinnen, T.; Fevery, B.; Tambuyzer, L.; Vijgen, L.; Peeters, M.; Buelens, A.; Ceulemans, H.; Beumont, M.; Picchio, G.; et al. 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. [Google Scholar] [CrossRef] [Green Version]
- Di Maio, V.C.; Cento, V.; Lenci, I.; Aragri, M.; Rossi, P.; Barbaliscia, S.; Melis, M.; Verucchi, G.; Magni, C.F.; Teti, E.; et al. Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies. Liver Int. 2017, 37, 514–528. [Google Scholar] [CrossRef]
- Lontok, E.; Harrington, P.; Howe, A.; Kieffer, T.; Lennerstrand, J.; Lenz, O.; McPhee, F.; Mo, H.; Parkin, N.; Pilot-Matias, T.; et al. Hepatitis C virus drug resistance-associated substitutions: State of the art summary. Hepatology 2015, 62, 1623–1632. [Google Scholar] [CrossRef]
- McPhee, F.; Hernandez, D.; Yu, F.; Ueland, J.; Monikowski, A.; Carifa, A.; Falk, P.; Wang, C.; Fridell, R.; Eley, T.; et al. Resistance analysis of hepatitis C virus genotype 1 prior treatment null responders receiving daclatasvir and asunaprevir. Hepatology 2013, 58, 902–911. [Google Scholar] [CrossRef]
- Manns, M.; Pol, S.; Jacobson, I.M.; Marcellin, P.; Gordon, S.C.; Peng, C.Y.; Chang, T.T.; Everson, G.T.; Heo, J.; Gerken, G.; et al. All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: A multinational, phase 3, multicohort study. Lancet 2014, 384, 1597–1605. [Google Scholar] [CrossRef]
- Harper, S.; McCauley, J.A.; Rudd, M.T.; Ferrara, M.; DiFilippo, M.; Crescenzi, B.; Koch, U.; Petrocchi, A.; Holloway, M.K.; Butcher, J.W.; et al. Discovery of MK-5172, a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor. ACS Med. Chem. Lett. 2012, 3, 332–336. [Google Scholar] [CrossRef] [Green Version]
- Summa, V.; Ludmerer, S.W.; McCauley, J.A.; Fandozzi, C.; Burlein, C.; Claudio, G.; Coleman, P.J.; Dimuzio, J.M.; Ferrara, M.; Di Filippo, M.; et al. 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. [Google Scholar] [CrossRef] [Green Version]
- Komatsu, T.E.; Boyd, S.; Sherwat, A.; Tracy, L.; Naeger, L.K.; O’Rear, J.J.; Harrington, P.R. Regulatory Analysis of Effects of Hepatitis C Virus NS5A Polymorphisms on Efficacy of Elbasvir and Grazoprevir. Gastroenterology 2017, 152, 586–597. [Google Scholar] [CrossRef]
- Zeuzem, S.; Ghalib, R.; Reddy, K.R.; Pockros, P.J.; Ben Ari, Z.; Zhao, Y.; Brown, D.D.; Wan, S.; DiNubile, M.J.; Nguyen, B.Y.; et al. Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann. Intern. Med. 2015, 163, 1–13. [Google Scholar] [CrossRef] [PubMed]
- Feld, J.J.; Kowdley, K.V.; Coakley, E.; Sigal, S.; Nelson, D.R.; Crawford, D.; Weiland, O.; Aguilar, H.; Xiong, J.; Pilot-Matias, T.; et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N. Engl. J. Med. 2014, 370, 1594–1603. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ferenci, P.; Bernstein, D.; Lalezari, J.; Cohen, D.; Luo, Y.; Cooper, C.; Tam, E.; Marinho, R.T.; Tsai, N.; Nyberg, A.; et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N. Engl. J. Med. 2014, 370, 1983–1992. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schnell, G.; Tripathi, R.; Beyer, J.; Reisch, T.; Krishnan, P.; Lu, L.; Dekhtyar, T.; Hall, C.; Vilchez, R.A.; Pilot-Matias, T.; et al. Hepatitis C virus genotype 4 resistance and subtype demographic characterization of patients treated with ombitasvir plus paritaprevir/ritonavir. Antimicrob. Agents. Chemother. 2015, 59, 6807–6815. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ng, T.; Reisch, T.; Middleton, T. ABT-493, a potent HCV NS3/4A protease inhibitor with broad genotype coverage (Abstract 636). In Proceedings of the Conference on Retroviruses and Opportunistic Infections (CROI), Boston, MA, USA, 3–6 March 2014. [Google Scholar]
- Krishnan, P.; Pilot-Matias, T.; Schnell, G.; Tripathi, R.; Ng, T.; Reisch, T.; Beyer, J.; Dekhtyar, T.; Irvin, M.; Xie, W.; et al. Pooled resistance analysis in HCV genotype 1–6-infected patients treated with glecaprevir/pibrentasvir in phase 2 and 3 clinical trials. J. Hepatol. 2017, 66, S500. [Google Scholar] [CrossRef]
- Nettles, J.H.; Stanton, R.A.; Broyde, J.; Amblard, F.; Zhang, H.; Zhou, L.; Shi, J.; McBrayer, T.R.; Whitaker, T.; Coats, S.J.; et al. Asymmetric binding to NS5A by daclatasvir (BMS-790052) and analogs suggests two novel modes of HCV inhibition. J. Med. Chem. 2014, 57, 10031–10043. [Google Scholar] [CrossRef] [Green Version]
- McGivern, D.R.; Masaki, T.; Williford, S.; Ingravallo, P.; Feng, Z.; Lahser, F.; Asante-Appiah, E.; Neddermann, P.; De Francesco, R.; Howe, A.Y.; et al. Kinetic analyses reveal potent and early blockade of hepatitis C virus assembly by NS5A inhibitors. Gastroenterology 2014, 147, 453–462.e7. [Google Scholar] [CrossRef]
- Bradshaw, D.; Mbisa, J.L.; Geretti, A.M.; Healy, B.J.; Cooke, G.S.; Foster, G.R.; Thomson, E.C.; McLauchlan, J.; Agarwal, K.; Sabin, C.; et al. Consensus recommendations for resistance testing in the management of chronic hepatitis C virus infection: Public Health England HCV Resistance Group. J. Infect. 2019, 79, 503–512. [Google Scholar] [CrossRef]
- Jeong, Y.; Jin, B.; Lee, H.W.; Park, H.J.; Park, J.Y.; Kim, D.Y.; Han, K.H.; Ahn, S.H.; Kim, S. Evolution and persistence of resistance-associated substitutions of hepatitis C virus after direct-acting antiviral treatment failures. J. Viral. Hepat. 2018, 25, 1251–1259. [Google Scholar] [CrossRef]
- Di Maio, V.C.; Cento, V.; Aragri, M.; Paolucci, S.; Pollicino, T.; Coppola, N.; Bruzzone, B.; Ghisetti, V.; Zazzi, M.; Brunetto, M.; et al. Frequent NS5A and multiclass resistance in almost all HCV genotypes at DAA failures: What are the chances for second-line regimens? J. Hepatol. 2018, 68, 597–600. [Google Scholar] [CrossRef] [Green Version]
- Leroy, V.; Angus, P.; Bronowicki, J.P.; Dore, G.J.; Hezode, C.; Pianko, S.; Pol, S.; Stuart, K.; Tse, E.; McPhee, F.; et al. Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: A randomized phase III study (ALLY-3+). Hepatology 2016, 63, 1430–1441. [Google Scholar] [CrossRef]
- Wang, C.; Jia, L.; Ii, D.R.O.; Sun, J.-H.; Rigat, K.; Valera, L.; Nower, P.; Huang, X.; Kienzle, B.; Roberts, S.; et al. Comparison of Daclatasvir Resistance Barriers on NS5A from Hepatitis C Virus Genotypes 1 to 6: Implications for Cross-Genotype Activity. Antimicrob. Agents Chemother. 2014, 58, 5155–5163. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Harrington, P.R.; Komatsu, T.E.; Deming, D.J.; Donaldson, E.F.; O’Rear, J.J.; Naeger, L.K. Impact of hepatitis C virus polymorphisms on direct-acting antiviral treatment efficacy: Regulatory analyses and perspectives. Hepatology 2018, 67, 2430–2448. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Forns, X.; Gordon, S.C.; Zuckerman, E.; Lawitz, E.; Calleja, J.L.; Hofer, H.; Gilbert, C.; Palcza, J.; Howe, A.Y.; DiNubile, M.J.; et al. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. J. Hepatol. 2015, 63, 564–572. [Google Scholar] [CrossRef] [PubMed]
- Jacobson, I.M.; Lawitz, E.; Kwo, P.Y.; Hézode, C.; Peng, C.Y.; Howe, A.Y.M.; Hwang, P.; Wahl, J.; Robertson, M.; Barr, E.; et al. Safety and Efficacy of Elbasvir/Grazoprevir in Patients With Hepatitis C Virus Infection and Compensated Cirrhosis: An Integrated Analysis. Gastroenterology 2017, 152, 1372–1382.e2. [Google Scholar] [CrossRef] [Green Version]
- Abergel, A.; Metivier, S.; Samuel, D.; Jiang, D.; Kersey, K.; Pang, P.S.; Svarovskaia, E.; Knox, S.J.; Loustaud-Ratti, V.; Asselah, T. Ledipasvir plus sofosbuvir for 12 weeks in patients with hepatitis C genotype 4 infection. Hepatology 2016, 64, 1049–1056. [Google Scholar] [CrossRef]
- Kitrinos, K.M.; Corsa, A.C.; Worth, A.; Hedskog, C.; Brainard, D.M.; Miller, M.D.; Mo, H. Nonstructural protein 5A resistance profile in patients with chronic hepatitis C treated with ledipasvir-containing regimens without sofosbuvir. J. Viral. Hepat. 2018, 25, 126–133. [Google Scholar] [CrossRef]
- Wyles, D.; Dvory-Sobol, H.; Svarovskaia, E.S.; Doehle, B.P.; Martin, R.; Afdhal, N.H.; Kowdley, K.V.; Lawitz, E.; Brainard, D.M.; Miller, M.D.; et al. Post-treatment resistance analysis of hepatitis C virus from phase II and III clinical trials of ledipasvir/sofosbuvir. J. Hepatol. 2017, 66, 703–710. [Google Scholar] [CrossRef]
- Krishnan, P.; Tripathi, R.; Schnell, G.; Reisch, T.; Beyer, J.; Irvin, M.; Xie, W.; Larsen, L.; Cohen, D.; Podsadecki, T.; et al. Resistance analysis of baseline and treatment-emergent variants in hepatitis C virus genotype 1 in the AVIATOR study with paritaprevir-ritonavir, ombitasvir, and dasabuvir. Antimicrob. Agents. Chemother. 2015, 59, 5445–5454. [Google Scholar] [CrossRef] [Green Version]
- Poordad, F.P.S.; Asatryan, A. 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. J. Hepatol. 2017, 66, S83–S84. [Google Scholar] [CrossRef]
- Pilot-Matias, T.K.P.; Schnell, G. 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. J. Hepatol. 2017, 66, S708–S709. [Google Scholar] [CrossRef]
- de Salazar, A.; Dietz, J.; di Maio, V.C.; Vermehren, J.; Paolucci, S.; Müllhaupt, B.; Coppola, N.; Cabezas, J.; Stauber, R.E.; Puoti, M.; et al. Prevalence of resistance-associated substitutions and retreatment of patients failing a glecaprevir/pibrentasvir regimen. J. Antimicrob. Chemother. 2020, 75, 3349–3358. [Google Scholar] [CrossRef] [PubMed]
- Feld, J.J.; Jacobson, I.M.; Hézode, C.; Asselah, T.; Ruane, P.J.; Gruener, N.; Abergel, A.; Mangia, A.; Lai, C.L.; Chan, H.L.; et al. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N. Engl. J. Med. 2015, 373, 2599–2607. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Foster, G.R.; Afdhal, N.; Roberts, S.K.; Bräu, N.; Gane, E.J.; Pianko, S.; Lawitz, E.; Thompson, A.; Shiffman, M.L.; Cooper, C.; et al. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N. Engl. J. Med. 2015, 373, 2608–2617. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hezode, C.; Reau, N.; Svarovskaia, E.S.; Doehle, B.P.; Shanmugam, R.; Dvory-Sobol, H.; Hedskog, C.; McNally, J.; Osinusi, A.; Brainard, D.M.; et al. Resistance analysis in patients with genotype 1-6 HCV infection treated with sofosbuvir/velpatasvir in the phase III studies. J. Hepatol. 2018, 68, 895–903. [Google Scholar] [CrossRef]
- Lam, A.M.; Espiritu, C.; Bansal, S.; Micolochick Steuer, H.M.; Niu, C.; Zennou, V.; Keilman, M.; Zhu, Y.; Lan, S.; Otto, M.J.; et al. Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus. Antimicrob. Agents. Chemother. 2012, 56, 3359–3368. [Google Scholar] [CrossRef] [Green Version]
- Vermehren, J.; Park, J.S.; Jacobson, I.M.; Zeuzem, S. Challenges and perspectives of direct antivirals for the treatment of hepatitis C virus infection. J. Hepatol. 2018, 69, 1178–1187. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Donaldson, E.F.; Harrington, P.R.; O’Rear, J.J.; Naeger, L.K. Clinical evidence and bioinformatics characterization of potential hepatitis C virus resistance pathways for sofosbuvir. Hepatology 2015, 61, 56–65. [Google Scholar] [CrossRef]
- Svarovskaia, E.S.; Dvory-Sobol, H.; Parkin, N.; Hebner, C.; Gontcharova, V.; Martin, R.; Ouyang, W.; Han, B.; Xu, S.; Ku, K.; et al. 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. 2014, 59, 1666–1674. [Google Scholar] [CrossRef] [Green Version]
- Svarovskaia, E.S.; Gane, E.; Dvory-Sobol, H.; Martin, R.; Doehle, B.; Hedskog, C.; Jacobson, I.M.; Nelson, D.R.; Lawitz, E.; Brainard, D.M.; et al. L159F and V321A Sofosbuvir-Associated Hepatitis C Virus NS5B Substitutions. J. Infect. Dis. 2016, 213, 1240–1247. [Google Scholar] [CrossRef] [Green Version]
- Chen, Q.; Perales, C.; Soria, M.E.; García-Cehic, D.; Gregori, J.; Rodríguez-Frías, F.; Buti, M.; Crespo, J.; Calleja, J.L.; Tabernero, D.; et al. Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure. Antiviral. Res. 2020, 174, 104694. [Google Scholar] [CrossRef]
- Bourlière, M.; Gordon, S.C.; Flamm, S.L.; Cooper, C.L.; Ramji, A.; Tong, M.; Ravendhran, N.; Vierling, J.M.; Tran, T.T.; Pianko, S.; et al. Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection. N. Engl. J. Med. 2017, 376, 2134–2146. [Google Scholar] [CrossRef]
- Sarrazin, C.; Cooper, C.; Manns, M.; Reddy, R.; Kowdley, K.; Dvory-Sobol, H.; Svarovskia, E.; Martin, R.; Doehle, B.; Camus, G.; et al. No impact of RASs on the high efficacy of SOF/VEL/VOX for 12 weeks in DAA-experienced patients: An integrated resistance analysis of the POLARIS-1 and POLARIS-4 studies. J. Hepatol. 2017, 66, S299. [Google Scholar] [CrossRef]
- de Lédinghen, V.; Laforest, C.; Hézode, C.; Pol, S.; Renault, A.; Alric, L.; Larrey, D.; Métivier, S.; Tran, A.; Jézéquel, C.; et al. Retreatment With Sofosbuvir Plus Grazoprevir/Elbasvir Plus Ribavirin of Patients With Hepatitis C Virus Genotype 1 or 4 Who Previously Failed an NS5A- or NS3-Containing Regimen: The ANRS HC34 REVENGE Study. Clin. Infect. Dis. 2018, 66, 1013–1018. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chevaliez, S.; Trimoulet, P.; Dorival, C.; Larrat, S.; Scholtes, C.; Meritet, J.-F.; Tuaillon, E.; Bocket, L.; Carrat, F.; Pol, S.; et al. Effect of resistance-associated substitutions on retreatment of direct acting antiviral-exposed patients in the real-world setting (ANRS CO22 HEPATHER). J. Hepatol. 2017, 66, S84. [Google Scholar] [CrossRef]
- Sarrazin, C. Treatment failure with DAA therapy: Importance of resistance. J. Hepatol. 2021, 74, 1472–1482. [Google Scholar] [CrossRef] [PubMed]
- Dietz, J.; Di Maio, V.C.; de Salazar, A.; Merino, D.; Vermehren, J.; Paolucci, S.; Kremer, A.E.; Lara, M.; Pardo, M.R.; Zoller, H.; et al. Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy. J. Hepatol. 2021, 74, 801–810. [Google Scholar] [CrossRef] [PubMed]
- Jensen, S.B.; Fahnøe, U.; Pham, L.V.; Serre, S.B.N.; Tang, Q.; Ghanem, L.; Pedersen, M.S.; Ramirez, S.; Humes, D.; Pihl, A.F.; et al. Evolutionary Pathways to Persistence of Highly Fit and Resistant Hepatitis C Virus Protease Inhibitor Escape Variants. Hepatology 2019, 70, 771–787. [Google Scholar] [CrossRef] [PubMed]
- Smith, D.A.; Bradshaw, D.; Mbisa, J.L.; Manso, C.F.; Bibby, D.F.; Singer, J.B.; Thomson, E.C.; da Silva Filipe, A.; Aranday-Cortes, E.; Ansari, M.A.; et al. Real world SOF/VEL/VOX retreatment outcomes and viral resistance analysis for HCV patients with prior failure to DAA therapy. J. Viral. Hepat. 2021, 28, 1256–1264. [Google Scholar] [CrossRef]
- Wang, G.P.; Schnell, G.L.; Kort, J.J.; Sidhu, G.S.; Schuster, L.; Tripathi, R.L.; Larsen, L.; Michael, L.C.; Bergquist, K.; Magee, A.; et al. Linkage of resistance-associated substitutions in GT1 sofosbuvir+NS5A inhibitor failures treated with glecaprevir/pibrentasvir. J. Hepatol. 2021, 75, 820–828. [Google Scholar] [CrossRef]
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Malandris, K.; Kalopitas, G.; Theocharidou, E.; Germanidis, G. The Role of RASs /RVs in the Current Management of HCV. Viruses 2021, 13, 2096. https://doi.org/10.3390/v13102096
Malandris K, Kalopitas G, Theocharidou E, Germanidis G. The Role of RASs /RVs in the Current Management of HCV. Viruses. 2021; 13(10):2096. https://doi.org/10.3390/v13102096
Chicago/Turabian StyleMalandris, Konstantinos, Georgios Kalopitas, Eleni Theocharidou, and Georgios Germanidis. 2021. "The Role of RASs /RVs in the Current Management of HCV" Viruses 13, no. 10: 2096. https://doi.org/10.3390/v13102096
APA StyleMalandris, K., Kalopitas, G., Theocharidou, E., & Germanidis, G. (2021). The Role of RASs /RVs in the Current Management of HCV. Viruses, 13(10), 2096. https://doi.org/10.3390/v13102096