NS5b GT1a
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Dasabuvir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
| WT (1a_H77) | 7.7 | 1x | likely susceptible | | 1 | |
| V11I | | | | | | |
| K51R | | | | | | |
| D61G | | | | | | |
| S62N | | | | | | |
| D66G | | | | | | |
| F101L | | | | | | |
| C110S | | | | | | |
| A112T | | | | | | |
| A117S | | | | | | |
| N142T | | | | | | |
| L159F | | | | | | |
| E202G | | | | | | |
| Q206K | | | | | | |
| N231A (GT1c/1h) [Conflicting WT, not used in algorithm] | | | | | | |
| E237G | | | | | | |
| V253I (GT1c/1h) [Conflicting WT, not used in algorithm] | | | | | | |
| K254R | | | | | | |
| S282G | | | | | | |
| S282R | | | | | | |
| S282T | | 1x | likely susceptible | | 7 | |
| R300Q | | | | | | |
| G307R | | 1x | resistance possible | Yes | 7,1 | Clinical TE RAV (1,7) |
| L314H | | 114x | resistance likely | | 6 | |
| C316H | | | | | | |
| C316R | | | | | | |
| C316Y | | 1472x | resistance likely | Yes | 4, 2,5,6,1,7 | clinical VF RAV (1,2,5,6,7) |
| L320F | | | | | | |
| L320I | | | | | | |
| L320S | | | | | | |
| L320V | | | | | | |
| V321A | | | | | | |
| V321F | | | | | | |
| V321I | | | | | | |
| S335N | | | | | | |
| Q355H | | | | | | |
| S368T | | 2x | likely susceptible | | 3 | |
| M36L [Conflicting WT, not used in algorithm] | | | | | | |
| T390I | | | | | | |
| A395G | | 20x | resistance likely | | 3,7 | |
| M414I | | 17x | resistance likely | | 6,4,3,1,7 | |
| M414T | 31 | 32x | resistance likely | Yes | 4,1,2,5,6,7 | clinical TE RAV (1,2,5,6,7) |
| M414V | | 18x | resistance likely | | 6,3,7 | |
| F415Y | | | | Yes | | asso with RBV VF (7), not RAS |
| A421T | 0.7 | 1x | likely susceptible | | 7 | |
| A421V | 0.8 | 1x | likely susceptible | | 7 | |
| N444K | 150 | 23x | resistance likely | | 3,7 | |
| D444N [Conflicting WT, not used in algorithm] | | | | | | |
| E446K | 52 | 54x | resistance likely | Yes | 1,5,6,7 | Clinical TE RAV (1,5,7) |
| E446Q | 17 | 17x | resistance likely | Yes | 1,5,6,7 | Clinical TE RAV (1,5,7) |
| Y448C | 2600 | 400x | resistance likely | | 3,6,7 | |
| Y448H | 936 | 975x | resistance likely | | 4, 3, 5,6,7 | |
| A450V | 2.9 | 3x | resistance possible | Yes | 1,7 | Clinical TE RAV (1,7) |
| C451R | | 1x | likely susceptible | | 3,6,7 | unfit (6,7) |
| R465G | | | | | | potential RAS (7) |
| R465T | | | | | | potential RAS (7) |
| S473T | | | | | | |
| R531K | | | | | | |
| G543S | | | | | | |
| A553I | | | resistance possible | Yes | 1 | clinical TE RAV (1) |
| A553T | 146 | 152x | resistance likely | Yes | 4, 2, 1, 5,6,7 | clinical TE RAV (2,1,5,7) |
| A553V | | 120x | resistance likely | Yes | 1,6 | clinical TE RAV (1) |
| G554D | 2.5 | 3x | likely susceptible | | 7 | |
| G554S | 190 | 198x | resistance likely | Yes | 4,2,5,6,1,7 | clinical TE RAV (4, 2,5,7) |
| Y555H | unfit | | | | 6 | |
| S556G | 29 | 30x | resistance likely | Yes | 4, 2, 3,5,6,1,7 | clinical TE RAV (2,1,5,6,7) |
| S556R | 251 | 261x | resistance likely | Yes | 3,5,6,1,7 | clinical TE RAV (1,5,7) |
| G558R | unfit | | resistance possible | Yes | 2,1,5,6,7 | Clinical TE RAB (7) |
| D559G | unfit | | resistance possible | Yes | 2,1,5,6,7 | clinical TE RAV (2,1,5,7) |
| D559I | | | resistance possible | Yes | 1,7 | clinical TE RAV (1,7) |
| D559N | unfit | | resistance possible | Yes | 1, 5,6,7 | clinical TE RAV (1,5,7) |
| D559V | | | resistance possible | Yes | 1,7 | clinical TE RAV (1,7) |
| Y561H | 20 | 21x | resistance likely | Yes | 5,1,6,7 | clinical TE RAV (1,5,6,7) |
| Y561N | unfit | | | | 6 | |
| L588F | | | resistance possible | Yes | 7 | Clinical TE RAV (7) |
| N590 del | | | | | | |
| C316Y+C110S | 1740 | 270x | resistance likely | | 3,7 | |
| C316Y+S431G | 1060 | 160x | resistance likely | | 3,7 | |
| C316Y+S556G | 2788 | 2904x | resistance likely | | 7 | |
| V405I+S556N | | 29x | resistance likely | | 3 | |
| V405I+S565F | | 17x | resistance likely | | 3 | |
| M414I+S556R | 980 | 1021x | resistance likely | | 7 | |
| M414I+S556G | 225 | 234x | resistance likely | | 7 | |
| M414T+A450V | 29 | 30x | resistance likely | | 7 | |
| M414T+S556G | 1042 | 1085x | resistance likely | | 7 | |
| M414T+S556R | 4583 | 4774x | resistance likely | | 7 | |
| A450V+M414T | 29 | 30x | resistance likely | | 7 | |
| D556N+V405I | 190 | 29x | resistance likely | | 7 | |
| S565F+V405I | 110 | 17x | resistance likely | | 7 | |
| D559G+Q19E | 780 | 150x | resistance likely | | 3,7 | |
| G307R+E446K+A450V+G554S+ G 558R [used in algorithm] | | >200x | resistance likely | Yes | 1 | clinical TE RAV (1) |
| G307R+E446Q+A450V+G554S+ G 558R [used in algorithm] | | >200x | resistance likely | Yes | 1 | clinical TE RAV (1) |
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| 1.Viekira Pak US Product Label Jan 28, 2016 |
| 2. Krishnan et al (2015) AAC 59(9);5445-5453 |
| 3.Koev et al. EASL 2009. Copenhagen, Denmark |
| 4. Lontok et al. (2015) Hepatology in press |
| 5. Holkira Canadian Product Monograph Oct 14, 2015 |
| 6. Sulkowski et al (2016) CROI poster 16LB-3113 |
| 7. FDA Microbiology/Virology Review_Veikira Pak_206619Orig1s000 |
Sofosbuvir
| Mutation | EC50 (uM) | Fold-shift | Phenotype | Replicatin Fitness | Clinical RAS | Reference | Comments |
| WT (1a_H77) | 0.044 | 1x | likely susceptible | 100 | | 2,3,6 | 0.044 - 0.062 nM |
| V11I | | | | 2.15 | | 15 | |
| K51R | | | | | | | |
| D61G | | | resistance possible | | Yes | 3,12 | clinical TE RAV (3,12) |
| S62N | | | resistance possible | | Yes | 13 | Clinical VF RAS (13) |
| D66G | | | resistance possible | | Yes | | Clinical TE RAS (12) |
| F101L | | | resistance possible | | Yes | 13 | Clincal TE RAS (13) |
| C110S | | 1.1x | likely susceptible | 292 | | 15 | |
| A112T | | | resistance possible | | Yes | 3, 4,12,14 | clinical TE RAV (3, 4,12,14) |
| A117S | | 1.1x | likely susceptible | 257 | | 15 | |
| N142T | | | resistance possible | | Yes | 9, 6,10 | Clinical TE RAV (9) |
| L159F | | 1.2x | resistance possible | 8.9 | Yes | 15,3, 4,1,6,5,8,12,13,14 | clinical TE RAV (1,3, 4,5,12,13,14) |
| E202G | | | resistance possible | | Yes | 13 | Clincal TE RAV (13) |
| Q206K | | 1.1x | likely susceptible | 106 | | 15 | |
| N231A (GT1c/1h) [Conflicting WT, not used in algorithm] | | | resistance possible | | Yes | 13 | Clincal TE RAV (13). GT1c/1h |
| E237G | | | resistance possible | | Yes | 6,4,12,14 | clincal TE RAV (6,4, 7,12,14) |
| V253I (GT1c/1h) [Conflicting WT, not used in algorithm] | | | resistance possible | | Yes | 13 | Clincal TE RAV (13), pts inf. with GT1c/1h |
| K254R | | 1.1x | likely susceptible | 88 | | 15 | |
| S282G | | | resistance likely | | Yes | 11,6 | clincal TE RAV, 2% (11) |
| S282R | | | resistance likely | | | 8 | EASL 2016 guidelines |
| S282T | 0.57 | 13x | resistance likely | | Yes | 2,3, 4,1,9,12 | clinical TE RAV (1,3, 4,6,12) |
| R300Q | | 0.9x | likely susceptible | 146 | | 15 | |
| G307R | | | | | | | |
| L314H | | | | | | | |
| C316H | | | resistance possible | | Yes | 12 | Clinical VF RAS (12) |
| C316R | | | resistance possible | | Yes | 13 | Clinical VF RAS (13) |
| C316Y | | | | | | | |
| L320F | | | | | | 8 | EASL 2016 guidelines |
| L320I | | | resistance possible | | Yes | 12,8 | Clincial TE RAS (12) |
| L320S | | | | | | 6,8 | |
| L320V | 0.07 | 1.8x | resistance possible | | Yes | 12,3 | clinical TE RAV (12,3) |
| V321A | | | resistance possible | | Yes | 1,8,12 | clincial VF RAV (1,12), not likely |
| V321F | | | resistance possible | | Yes | | cliincal TE RAV, 1% (11) |
| V321I | 0.048 | 1.2x | resistance possible | | Yes | 3,12 | clinical TE RAV (3,12), not likely |
| S335N | | 1,2x | likely susceptible | 186 | | 15 | |
| Q355H | | | resistance possible | | Yes | 4,14 | clinical TE RAV ( 4,14) |
| S368T | | | | | | | |
| M36L [Conflicting WT, not used in algorithm] | | | resistance possible | | Yes | 12 | clincal TE RAS (12) |
| T390I | | 0.9x | likely susceptible | 192 | | 15 | |
| A395G | | | | | | | |
| M414I | | | | | | | |
| M414T | | | | | | | |
| M414V | | | | | | | |
| F415Y | | 2.3x | resistance possible | | Yes | 12 | Clinical VF RAS (12) |
| A421T | | | | | | | |
| A421V | | | | | | | |
| N444K | | | | | | | |
| D444N [Conflicting WT, not used in algorithm] | | | resistance possible | | Yes | 13 | Clincial TE RAS (13) |
| E446K | | | | | | | |
| E446Q | | | | | | | |
| Y448C | | | | | | | |
| Y448H | | | | | | | |
| A450V | | | | | | | |
| C451R | | | | | | | |
| R465G | | | | | | | |
| R465T | | | | | | | |
| S473T | | | resistance possible | | Yes | 3,12 | clinical TE RAV (3,12) |
| R531K | | 1.1x | likely susceptible | 121 | | 15 | |
| G543S | | 0.9x | likely susceptible | 159 | | 15 | |
| A553I | | | | | | | |
| A553T | | | | | | | |
| A553V | | | | | | | |
| G554D | | | | | | | |
| G554S | | | | | | | |
| Y555H | | | | | | | |
| S556G | | | | | | | |
| S556R | | | | | | | |
| G558R | | | | | | | |
| D559G | | | | | | | |
| D559I | | | | | | | |
| D559N | | | | | | | |
| D559V | | | | | | | |
| Y561H | | | | | | | |
| Y561N | | | | | | | |
| L588F | | | | | | | |
| N590 del | | | resistance possible | | Yes | 14 | Clinical TE RAS |
| C316Y+C110S | | | | | | | |
| C316Y+S431G | | | | | | | |
| C316Y+S556G | | | | | | | |
| V405I+S556N | | | | | | | |
| V405I+S565F | | | | | | | |
| M414I+S556R | | | | | | | |
| M414I+S556G | | | | | | | |
| M414T+A450V | | | | | | | |
| M414T+S556G | | | | | | | |
| M414T+S556R | | | | | | | |
| A450V+M414T | | | | | | | |
| D556N+V405I | | | | | | | |
| S565F+V405I | | | | | | | |
| D559G+Q19E | | | | | | | |
| G307R+E446K+A450V+G554S+ G 558R [used in algorithm] | | | | | | | |
| G307R+E446Q+A450V+G554S+ G 558R [used in algorithm] | | | | | | | |
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| 1. Lontok et al. (2015) Hepatology in press |
| 2. Lam et al (2012) AAC 56:3359-3368 |
| 3. Harvoni US Product Label |
| 4. Daklinza US Product Label Feb 2016 |
| 5. Donaldson (2015) Hepatology 61:56-65 |
| 6. Sarrazin (2014) AASLD Poster #1926 |
| 7. Chariton (2016) EASL PS099 |
| 8. EASL Guidelines 2016 |
| 9. Sovaldi Product Label (2015) |
| 10. McPhee, F et al. (2017) Antiviral Therapy 22.3:237-246 |
| 11. FDA Vosevi Microbiology Reviews 209195Orig1s000MicroR |
| 12. FDA Microbiology/Virology Reviews Harvoni_Microbiology Reviews_205834Orig1a000MicroR |
| 13.FDA Microbiology/Virology Reviews Epclusa_ 208341Orig1s000 (2015) |
| 14. FDA NDA Microbiology Virology Reviews_Daklinza_206843Orig1s001, s003 |
| 15. Svarovskaia ES, et al. 2014. Clinical Infectious Diseases 59: 1666-74 |
