NS5b GT1b
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Dasabuvir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
| WT (GT1b_con 1) | 1.8 | 1x | likely susceptible | | 1 | |
| S96T | 1.4 | 2x | likely susceptible | | 7 | |
| N110S | | | | | | |
| T130N | | | | | | |
| N142S | | | | | | |
| L159F | | | | | | |
| S189P | | | | | | |
| K212R | | | | | | |
| S282G | | | | | | |
| S282R | | | | | | |
| S282T | 1.3 | 2x | likely susceptible | | 7 | |
| C316H | | 229x | resistance likely | Yes | 1,5,7 | Clinical VF RAV (7) |
| C316N | 3.2 | 5x | resistance likely | Yes | 1,6,5,7 | Clinical VF RAV (7) |
| C316W | unfit | | | | 5,7 | |
| C316Y | 926 | 1569x | resistance likely | Yes | 2,4,1,3,6,5,7 | clinical TE RAV (4,1,7) |
| I321V [Conflicting WT, not used in algorithm] | | | | | | |
| S335N | | | | | | |
| K355T | | | | | | |
| S368T | | 110x | resistance likely | | 3,1,5,7 | |
| N411S | | 54x | resistance likely | | 3,1,5,7 | |
| I413V | | | | | | potential RAS (7) |
| M414I | | 15x | resistance likely | Yes | 3, 4,1,5,7 | clinical TE RAV (1,7) |
| M414T | 190 | 270x | resistance likely | Yes | 7,3,1,6,5 | clinical TE RAV (1) |
| M414V | | 18x | resistance likely | | 3,5,7 | |
| F415Y | | | | | | asso with RBV VF (7), not RAS |
| M423T | 1 | 1x | likely susceptible | | 7,6 | |
| C445F | | 7x | resistance possible | | 5 | |
| Y448C | | 160x | resistance likely | | 3,1,5,7 | |
| Y448H | 70 | 100x | resistance likely | | 7,3,1,6,5 | replicon RAV (6) |
| C451S | | | | | | |
| A486V | | | | | | potential RAS (7) |
| P495A | 0.1 | 1x | likely susceptible | | 7,6 | |
| P495L | | | | | 6 | |
| P495S | 1.1 | 2x | likely susceptible | | 7,6 | |
| P496S | 0.6 | 1x | likely susceptible | | 7,6 | |
| V499A | 1.1 | 2x | likely susceptible | | 7,6 | |
| T520I | | | | | | |
| S549N | | | | | | |
| A553V | 71 | 120x | resistance likely | | 7,3,1,5 | |
| S556G | 6.5 | 11x | resistance likely | Yes | 3,2,1,6,5,7 | clinical TE RAV (1,7) |
| S556R | 21 | 3x | resistance possible | Yes | 1 | clinical TE RAV (1) |
| D559G | 65 | 100x | resistance likely | | 3,1,5,7 | |
| L564V | | | | | | |
| F193Y+Y586C | 320 | 39x | resistance likely | | 7 | 1b_N |
| L159F+C316N | | | | | | |
| C316H+V321I | 90 | 153x | resistance likely | | 7 | |
| C316N + S556G | 23 | 38x | resistance likely | | 7 | |
| C316Y+A376C | 870 | 1100x | resistance likely | | 7 | 1b_con1 |
| C316Y+L588F | 2600 | 3300x | resistance likely | | 7 | 1b_con1 |
| C316Y+M414I | 1544 | 2617x | resistance likely | | 7 | |
| C316Y+N117S | 3900 | 4800x | resistance likely | | 7 | 1b_con1 |
| C316Y+Y586C | 1500 | 1900x | resistance likely | | 7 | 1b_con1 |
| I392F+Y586C | 82 | 10x | resistance possible | | 7 | 1b_N |
| M414T+A435T | 240 | 29x | resistance likely | | 7 | 1b_N |
| M414T+F162T | 5.1 | 6x | resistance possible | | 7 | 1b_con1 |
| M414T+L587V | 140 | 17x | resistance likely | | 7 | 1b_N |
| Y448C+K81R | 2900 | 350x | resistance likely | | 7 | 1b_N |
| Y448H+E440G | 200 | 24x | resistance likely | | 7 | 1b_N |
| S556G+F551L | 1100 | 140 | resistance likely | | 7 | 1b_N |
| C316N+C451N+S556G | 104 | 176x | resistance likely | | 7 | |
| C316Y+K69R+N110S | 1600 | 2000x | resistance likely | | 3,7 | 1b_con1 |
| C316Y+M414I+Y448H | 2223 | 3768x | resistance likely | | 7 | |
| C316Y+M71I+S189P | 1500 | 1900x | resistance likely | | 7 | 1b_con1 |
| C445F+C451S+I585V | 12 | 16x | resistance likely | | 7 | 1b_con1 |
| Y448C+A442T+Y586C | 3900 | 480x | resistance likely | | 7 | 1b_N |
| Y448C+S506N+Y586C | 1040 | 130x | resistance likely | | 7 | 1b_N |
| D559G+H95R+S19G | 89 | 11x | resistance likely | | 7 | 1b_N |
| 1.Viekira Pak US Product Label Jan 28, 2016 |
| 2.Lontok et al. (2015) Hepatology in press |
| 3.Koev et al. EASL 2009. Copenhagen, Denmark |
| 4. Poordad et al (2014) NEJM 370 (21):1973 – 1982 |
| 5. Sulkowski et al (2016) CROI poster 16LB-3113 |
| 6. Holkira Canadian Product Monograph Oct 14, 2015 |
| 7. FDA Microbiology/Virology Review_Veikira Pak_206619Orig1s000 |
Sofosbuvir
| Mutation | EC50 (uM) | Fold-shift | Phenotype | Replicative Fitness (7) | Clinical RAS | Reference | Comments |
| WT (GT1b_con 1) | 0.048 | 1x | likely susceptible | 100 | | 1,2 | 0.048 - 0.1 nM |
| S96T | | | | | | | |
| N110S | | 0.9x | likely susceptible | 166 | | 8 | |
| T130N | | 1x | likely susceptible | 71 | | 8 | |
| N142S | | | resistance possible | | Yes | 3 | clinical VF RAV (3) |
| L159F | | 1.3x | likely susceptible | 24 | | 8,4 | EASL 2016 guidelines |
| S189P | | 1.2x | likely susceptible | 113 | | 8 | |
| K212R | | 1x | likely susceptible | 71 | | 8 | |
| S282G | | | resistance likely | | | | catalytic triad, potential seq artefact |
| S282R | | | resistance likely | | | | catalytic triad |
| S282T | 0.37 | 8.8x | resistance likely | 8.4 | Yes | 1,2,4,6 | Clinical TE RAS (6) |
| C316H | | | | | | | |
| C316N | | | | | | | |
| C316W | | | | | | | |
| C316Y | | | | | | | |
| I321V [Conflicting WT, not used in algorithm] | | | resistance possible | | Yes | 6 | Clinical VF RAS (6) |
| S335N | | 0.8x | likely susceptible | 66 | | 8 | |
| K355T | | | resistance possible | | Yes | 6 | Clinical TE RAS (6) |
| S368T | | | | | | | |
| N411S | | | | | | | |
| I413V | | | | | | | |
| M414I | | | | | | | |
| M414T | | | | | | | |
| M414V | | | | | | | |
| F415Y | | | | | | | |
| M423T | | | | | | | |
| C445F | | 1.6x | likely susceptible | 88 | | 7 | |
| Y448C | | | | | | | |
| Y448H | | | | | | | |
| C451S | | | | | | | |
| A486V | | | | | | | |
| P495A | | | | | | | |
| P495L | | | | | | | |
| P495S | | | | | | | |
| P496S | | | | | | | |
| V499A | | | | | | | |
| T520I | | 0.9x | likely susceptible | 76 | | 8 | |
| S549N | | 1x | likely susceptible | 81 | | 5 | |
| A553V | | | | | | | |
| S556G | | | | | | | |
| S556R | | | | | | | |
| D559G | | | | | | | |
| L564V | unfit | | | <0.1 | | 8 | |
| F193Y+Y586C | | | | | | | |
| L159F+C316N | | 1.6x | likely susceptible | 65 | | 8 | |
| C316H+V321I | | | | | | | |
| C316N + S556G | | | | | | | |
| C316Y+A376C | | | | | | | |
| C316Y+L588F | | | | | | | |
| C316Y+M414I | | | | | | | |
| C316Y+N117S | | | | | | | |
| C316Y+Y586C | | | | | | | |
| I392F+Y586C | | | | | | | |
| M414T+A435T | | | | | | | |
| M414T+F162T | | | | | | | |
| M414T+L587V | | | | | | | |
| Y448C+K81R | | | | | | | |
| Y448H+E440G | | | | | | | |
| S556G+F551L | | | | | | | |
| C316N+C451N+S556G | | | | | | | |
| C316Y+K69R+N110S | | | | | | | |
| C316Y+M414I+Y448H | | | | | | | |
| C316Y+M71I+S189P | | | | | | | |
| C445F+C451S+I585V | | | | | | | |
| Y448C+A442T+Y586C | | | | | | | |
| Y448C+S506N+Y586C | | | | | | | |
| D559G+H95R+S19G | | | | | | | |
| 1. Harvoni US Product Lable |
| 2. Lam et al (2012) AAC 56:3359-3368 |
| 3. Sarrazin (2014) AASLD Poster #1926 |
| 4. EASL Guidelines 2016 |
| 5. Xu S. et al (2016) In Vitro Selection of Resistance to Sofosbuvir in HCV Replicons of Genotype 1 Through 6 (submitted Antiviral Therapy) |
| 6. FDA Microbiology/Virology Reviews Harvoni_Microbiology Reviews_205834Orig1a000MicroR |
| 7. Xu et al. (2017) Antiviral therapy 22:587-97. |
| 8. Svarovskaia ES, et al. 2014. Clinical Infectious Diseases 59: 1666-74 |
