HCV NS3 Protease Drug Resistance

Transcription

1 test code: cpt code: category: Infectious Disease HCV genotypes 1a CODON Simeprevir 1a Boceprevir 1a Telaprevir 1a Paritaprevir 1a Grazoprevir 1a V36A Comment R 3 R 10, 11 R 16 S 24 V36C V36G V36I V36L R 3 R 16 S 24 V36M R 3, 9 R 10, 11 R 16 S 24 Q41R R 3 F43I F43L R 5, 16 F43S F43V T54A R 3, 9 T54C T54G T54S R 3, 9 S 16 V55A R 3, 9 R 20 S 24 V55I S 3, 9, 20 S 20 S 16 Q80H Q80K R 1, 8, 22 S 8 S 8 R 5, 16 S 24 Q80L S 1 R 16 Q80R R 1, 22 R 16 S 24 V107I S 9 S122R R 1 S138T R155G R 5, 16 R155I R155K R 1, 22, 25 R 3, 9, 25 R 10, 11, 17, 25 R 5, 16 R 24, 25 R155L R155M R155Q R 25 R 25 R 25 R 25 R 25 R155S R 5, 16 R155T R 3 R 16

2 HCV genotypes 1a CODON Simeprevir 1a Boceprevir 1a Telaprevir 1a Paritaprevir 1a Grazoprevir 1a R155W R 16 A156F A156G R 25 R 25 R 25 R 25 R 25 A156N A156S S 25 R 3, 25 R 10, 11, 25 R 25 R 25 A156T R 17 R 5, 16 A156V V158I R 3, 9 D168A R 1, 25 S 25 S 17, 25 R 5, R 24, 25 D168E R 1, 22 R 5, 16 R 24 D168F R 5 D168G R 24 D168H R 5, 16 D168I D168K D168N S 3 S 10, 11 R 5, 16 D168Q D168T D168V R 1 R 5, 16 D168Y R 5, 16 I170A I170M I170T * R 24 I170V R 9 M175L not applicable** *Low-grade or variable resistance. **Resistance to boceprevir has been noted in genotype 1b, however this substitution is not commonly found in genotype 1a. For the most up-to-date list of assays, please visit our website at This test was developed and its performance characteristics determined by Viracor Eurofins. It has not been cleared or approved by the U.S. Food and Drug Administration. The CPT codes provided are based on Viracor Eurofins interpretation of the American Medical Association s Current Procedural Terminology (CPT) codes and are provided for informational purposes only. CPT coding is the sole responsibility of the billing party. Questions regarding coding should be addressed to your local Medicare carrier. Viracor Eurofins assumes no responsibility for billing errors due to reliance on the CPT codes illustrated in this material.

3 HCV genotypes 1b CODON Simeprevir 1b Boceprevir 1b Telaprevir 1b Paritaprevir 1b Grazoprevir 1a V36A R 12 R 2, 3, 10, 12 R 4, 6, 10, 11, 21 R 23 V36C S 10 R 10 V36G R 10, 19 R 6, 10, 11, 19, 21 V36I R 2 S 6, 10, 11 V36L S 12 S 10, 12 R 6, 10, 11, 12, 21 S 24 V36M R 10, 12 R 2, 3, 6, 9, 10 R 4, 6, 10, 11, 12, 18, 21 S 24 Q41R S 6, 12 R 2, 3 S 10 R 23 F43I R 6, 12 S 12 F43L F43S R 6, 12 R 2, 3, 6, 12 R 12 R 24 F43V R 6, 12 R 12 T54A S 10, 12 R 2, 3, 6, 9, 10, 12, 19 R 4, 6, 10, 11, 12, 18, 19, 21 S 16 T54C R 2 T54G R 3 T54S S 12 R 2, 3, 9, 12, 19 R 4, 6, 10, 11, 19 V55A R 2, 3, 9, 19 R 10, 19 S 16 S 24 V55I R 2, 3, 9 Q80H R 6, 12 S 12 Q80K R 1, 6, 12, 13, 22 S 2, 12 S 12 Q80L S 1, 22 S 12 Q80R R 1, 6, 12, 22 S 12 S 10, 12 R 24 V107I R 9 S122R R 1, 6, 13 S138T R 12 S 12 R155G R 12 R 10, 12 R 6, 10, 11, 12 R 24 R155I S 12 R 10, 12 R 10 R155K R 1, 6, 10, 12, 22 R 2, 3, 6, 9, 10, 12, 19 R 4, 6, 10, 12, 19 R 16 R or S* 23, 24, 25 R155L R 19 R 19 R155M S 12 R 10, 12 R 6, 10, 11, 12 R155Q S 12 S 12 R 12 R155S R 10 R 10 R155T R 12 R 2, 10, 12 R 4, 6, 10, 11, 12, 18 R155W A156F R 6, 10, 11 A156G R 6, 12 R 12 S 12 A156N R 6, 10, 11 A156S S 10, 12 R 2, 3, 6, 12, 19 R 4, 6, 11, 12, 14, 18, 19 S 16 A156T R 6, 10, 12 R 2, 3, 6, 10, 12, 19 R 4, 6, 11, 12, 15, 19 R 5, 16 R 23, 24 A156V R 6, 12 R 2, 3, 10, 12 R 4, 6, 11, 12, 15 V158I R 2, 3, 9 D168A R 1, 6, 12 S 12 S 12, 14 R 5, 16 R 24

4 HCV genotypes 1b CODON Simeprevir 1b Boceprevir 1b Telaprevir 1b Paritaprevir 1b Grazoprevir 1a D168E R 1, 6, 12, 22 S 12 S 12 R 16 R 24 D168F D168G R 12 S 12 R 24 D168H R 6, 12 S 12 S 12 R 5, 16 D168I R 6, 12 S 12 D168K R 24 D168N R 6, 12 S 12 S 6, 10, 12 D168Q R 13 D168T R 6, 12 S 12 S 12 R 16 D168V R 1, 6, 12 S 3, 12 S 14 R 5, 16 D168Y R 6, 12 R 12 S 12 R 16 R 23 I170A S 12 R 2, 3, 6, 10, 12, 19 R 10, 19 S 16 I170M R 3 I170T R 8, 12 R or S* 2, 8, 12 S 8 S 24 I170V S 13 M175L R 2, 3, 9 Comment: Patient genotype (1a/1b) displayed a mutation that has shown resistance to (drug name) in genotype (1a/1b). This test was developed and its performance characteristics determined by Viracor Eurofins. It has not been cleared or approved by the U.S. Food and Drug Administration. Results should be used in conjunction with clinical findings, and should not form the sole basis for a diagnosis or treatment decision. For the most up-to-date list of assays, please visit our website at Viracor-Eurofins.com. This test was developed and its performance characteristics determined by Viracor Eurofins. It has not been cleared or approved by the U.S. Food and Drug Administration. The CPT codes provided are based on Viracor Eurofins interpretation of the American Medical Association s Current Procedural Terminology (CPT) codes and are provided for informational purposes only. CPT coding is the sole responsibility of the billing party. Questions regarding coding should be addressed to your local Medicare carrier. Viracor Eurofins assumes no responsibility for billing errors due to reliance on the CPT codes illustrated in this material.

5 HCV NS3 References 1. Product Insert, Simeprevir (Olysio) TM, HIGHLIGHTS OF PRESCRIBING INFORMATION. Nov Product Insert, Boceprevir (Victrelis) TM, HIGHLIGHTS OF PRESCRIBING INFORMATION. May Product Insert, Boceprevir (Victrelis) TM, HIGHLIGHTS OF PRESCRIBING INFORMATION. Revised July Product Insert, Telaprevir (Incivek), HIGHLIGHTS OF PRESCRIBING INFORMATION. May Product Insert, Paritaprevir (VIEKIRA PAK) TM, HIGHLIGHTS OF PRESCRIBING INFORMATION. Dec DRC Forum for Collaborative HIV Research, Clinically Relevant HCV Mutations, appendix linked in 8. Berger KL, Triki I, Cartier M, et al. Baseline hepatitis C virus (HCV) NS3 polymorphisms and their impact on treatment response in clinical studies of the HCV NS3 protease inhibitor faldaprevir. Antimicrob Agents Chemother. 2014;58(2): Howe JA, Long J, Black S, et al. Clinical Implications of Detectable Baseline Hepatitis C Virus-Genotype 1 NS3/4A-Protease Variants on the Efficacy of Boceprevir Combined With Peginterferon/Ribavirin. Open Forum Infect Dis Sep 16;1(2):ofu078. doi: /ofid/ofu078. ecollection Jiang M, Mani N, Lin C, et al. In vitro phenotypic characterization of hepatitis C virus NS3 protease variants observed in clinical studies of telaprevir. Antimicrob Agents Chemother Dec;57(12): Kieffer TL, De Meyer S, Bartels DJ, et al. Hepatitis C viral evolution in genotype 1 treatment-naïve and treatment-experienced patients receiving telaprevir-based therapy in clinical trials. PLoS One. 2012;7(4):e Lenz O, Verbinnen T, Lin TI, et al. In vitro resistance profile of the hepatitis C virus NS3/4A protease inhibitor TMC435. Antimicrob Agents Chemother May;54(5): Lenz O, Vijgen L, Berke JM, et al. Virologic response and characterisation of HCV genotype 2-6 in patients receiving TMC435 monotherapy (study TMC435-C202). J Hepatol Mar;58(3): Lin C, Lin K, Luong YP, et al. In vitro resistance studies of hepatitis C virus serine protease inhibitors, VX-950 and BILN 2061:structural analysis indicates different resistance mechanisms. J Biol Chem Apr;279(17): Lin C, Gates CA, Rao BG, et al. In vitro studies of cross-resistance mutations against two hepatitis C virus serine protease inhibitors, VX-950 and BILN J Biol Chem Nov 4;280(44): Pilot-Matias T, Tripathi R, Cohen D, et al. In Vitro and In Vivo Antiviral Activity and Resistance Profile of the Hepatitis C Virus NS3/4A Protease Inhibitor ABT-450. Antimicrob Agents Chemother Feb;59(2): Romano KP, Ali A, Aydin C, et al. The molecular basis of drug resistance against hepatitis C virus NS3/4A protease inhibitors. PLoS Pathog. 2012;8(7):e Sarrazin C, Kieffer TL, Bartels D, et al. Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology May;132(5): Susser S, Welsch C, Wang Y, et al. Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus-infected patients. Hepatology Dec;50(6): Welsch C, Schweizer S, Shimakami T, et al. Ketoamide resistance and hepatitis C virus fitness in val55 variants of the NS3 serine protease. Antimicrob Agents Chemother Apr;56(4): Zhou Y, Bartels DJ, Hanzelka BL, et al. Phenotypic characterization of resistant Val36 variants of hepatitis C virus NS3-4A serine protease. Antimicrob Agents Chemother Jan;52(1): Lenz O. Verbinnen T, Fevery B, et al. Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in Phase IIb/III studies. J of Hepatology May;62:

6 HCV NS3 References 23. Summa V, Ludmerer SW, McCauley JA, 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 Aug;56(8): doi: /AAC Epub 2012 May 21. Erratum in: Antimicrob Agents Chemother Aug;58(8):4995. Huang, Qian [added] 24. Howe AY, Black S, Curry S, et al. Virologic resistance analysis from a phase 2 study of MK-5172 combined with pegylated interferon/ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection. Clin Infect Dis Dec 15;59(12): Jensen SB, Serre SB, Humes DG, et al. Substitutions at NS3 Residue 155, 156, or 168 of Hepatitis C Virus Genotypes 2 to 6 Induce Complex Patterns of Protease Inhibitor Resistance. Antimicrob Agents Chemother Dec;59(12): MM 0085 REV2 1216