Download full data set for GT2
Daclatasvir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
|---|---|---|---|---|---|---|
| WT (2a_JFH_L31) [Use in algorithm] | 0.02 | 1x | likely susceptible | 1,2,5,6 | 0.02-18 (6) . Assume EC90 = 4xEC50 | |
| WT (2a_J6_M31) [Conflicting WT] | 19 | 268x | resistance likely | 2 | ||
| WT (GT2b_MD2b_L31) [Conflicting WT] | ||||||
| T24A (GT2b) [Not used in algorithm] | ||||||
| T24T (GT2b) [Not used in algorithm] | ||||||
| T 24Y (GT2b) [Used in algorithm] | ||||||
| T24A | 3 | EASL 2016 guidelines | ||||
| T24P | ||||||
| T24S | ||||||
| L27M | ||||||
| F28C | 8 | 400x | resistance likely | Yes | 5 | Clinical VF (5) |
| F28I | 0.2 | 10x | likely susceptible | 5 | ||
| F28L | 0.005 | <1x | likely susceptible | 5 | 2b/2a chimeric replicon | |
| F28S | 379 | 9133->7042x | resistance likely | 4,2,3,6 | ||
| F28V | ||||||
| L28F (GT2b) [Not used in algorithm] | ||||||
| L 28L (GT2b) [Not used in algorithm] | ||||||
| F 28M (GT2b) [Used in algorithm] | 3 | EASL 2016 guidelines | ||||
| F 28T (GT2b) [Used in algorithm] | ||||||
| L28V (GT2b) [Not used in algorithm] | 3 | EASL 2016 guidelines | ||||
| P29S | ||||||
| K30A | ||||||
| K30E | 0.014 | 0.9x | likely susceptible | 4 | ||
| K30G | ||||||
| K30H | 3 | EASL 2016 guidelines | ||||
| K30M (GT2b) | ||||||
| K30N (GT2b) | ||||||
| K30Q | 0.001 | 0.1x | likely susceptible | 4 | ||
| K30R | 0.05 | <2x | likely susceptible | 5 | ||
| K30S | 3 | EASL 2016 guidelines | ||||
| K30T | ||||||
| L 31I (GT2b_MD) [Used in algorithm] | ||||||
| M31I (GT2a_J6) [Not used in algorithm] | ||||||
| L 31M (GT2b_MD) [Used in algorithm] | 11 | 107-550x | resistance likely | Yes | 5,1,3,4,6 | Clinical VF (5) |
| L 31V (GT2b_MD) [Used in algorithm] | 3 | EASL 2016 guidelines | ||||
| M31V (GT2b) [Not used in algorithm] | ||||||
| S38F (GT2b) | ||||||
| K44R | ||||||
| R44K (GT2b) [Conflicting WT, not used in algorithm] | ||||||
| V52I (GT2b) [Conflicting WT, not used in algorithm] | ||||||
| P58A (GT2a) [Not used in algorithm] | ||||||
| P58A (GT2b) [Used in algorithm] | ||||||
| P58S (GT2b) | ||||||
| P58T | ||||||
| P58Q | ||||||
| N62V | ||||||
| N62S | ||||||
| C92A (GT2b) | ||||||
| C92K | ||||||
| C92N | ||||||
| C92R | 4.8 | 133x | resistance likely | 4,6 | 98-133x | |
| C92S (GT 2a) [Not used in algorithm] | ||||||
| C92S (GT2b) [Used in algorithm] | ||||||
| C92T (GT2a) [Not used in algorithm] | ||||||
| C92T (GT2b) [Used in algorithm] | ||||||
| C92Y | ||||||
| Y93C | ||||||
| Y93D | ||||||
| Y93F [Conflicting WT] | ||||||
| Y93F (GT2b) [Use in algorithm] | ||||||
| Y93H | 36.7 | 749-1750x | resistance likely | 5,4,6 | ||
| Y93L | ||||||
| Y93N | ||||||
| Y93S | ||||||
| Y93T | ||||||
| T24A+L31M | ||||||
| T24A+C92S | ||||||
| T24S+F28C | 5000 | 62,500x | resistance likely | Yes | 5 | Clincial VF(5), EC90 |
| T24S+L31M | 187 | 2337x | resistance likely | Yes | 5 | Clincial VF(5), EC90 |
| F28C+ L31M | 392 | 4900x | resistance likely | Yes | 5 | Clincial VF(5), EC90 |
| F28C+L31M | 200 | 10000x | resistance likely | 5 | ||
| F28L+C92S | 0.007 | <1X | likely susceptible | 5 | ||
| F28L+L31I | 1.3 | 65x | Resistance possible | 5 | 2b/2a chimera, assume WT=0.02 | |
| F28L+L31M | 13 | 650x | resistance likely | 4,5 | 2b/2a chimera, assume WT=0.02 | |
| F28S+L31M | 4513 | 56140x | resistance likely | Yes | 5 | Clincial VF(5), EC90 |
| F28S+L31I | ||||||
| L28F+M31L (GT2b) | ||||||
| L28F+L31V (GT2b) | ||||||
| P29S+K30G | ||||||
| K30E+C92R | 440x | resistance likely | 4 | |||
| K30Q+C92R | 0.007 | 0.4x | likely susceptible | 4 | ||
| K30R+L31M | 2.2 | 110X | resistance likely | 5 | ||
| L 31I+Y93H (GT2b) [Used in algorithm] | ||||||
| L 31V+Y93H (GT2b) [Used in algorithm] | ||||||
| L31M+P58S | ||||||
| L31M+C92S | 118 | 5900x | resistance likely | 5 | ||
| T24S+L31M+C92S | 1377 | 17212x | resistance likely | Yes | 5 | Clincial VF(5), EC90 |
| F28L+K30R+L31M | 2.5 | 125X | resistance likely | 5 | 2b/2a chimera, assume WT=0.02 | |
| F28K+K30R+L31V | 20 | 1000X | resistance likely | 5 | 2b/2a chimera, assume WT=0.02 | |
| F28K+L31M+C92A | 180 | 9000X | resistance likely | 5 | 2b/2a chimera, assume WT=0.02 | |
| F28K+L31M+C92S | 186 | 9300X | resistance likely | 5 | 2b/2a chimera, assume WT=0.02 | |
| F28S+L31M+C92S | >5000 | >250000 | resistance likely | 5 | ||
| F28L+K30R+L31M+C92S | 20 | 1000X | resistance likely | 5 | ||
| F28L+L31M+C92S | 206 | 2575x | resistance likely | Yes | 5 | Clinical VF, EC90FS |
| In virto Drug Susecptibility: | ||||||
| <20x FS , likely susceptible | ||||||
| 20-100X FS, resistance possible | ||||||
| >100 FS, resistance likely | ||||||
| Multiple RASs: | ||||||
| Data for variants with multiple mutations take precedence over est. from individual RASs | ||||||
| If variant data is not available, follow rules for individual RASs in the variant | ||||||
| 2 likely susceptible = likely susceptible | ||||||
| 2 resistance possible = resistance likely | ||||||
| likely susceptible + resistance possible = resistance possible | ||||||
| >/= 1 resistance likely RASs = resistance likely | ||||||
| Clinical RAV: | ||||||
| wihtout data but observed in Clinical VF = resistance possible | ||||||
| likely susceptible RASs + clinical RAV = resistance possible | ||||||
| resistance possible RASs + clinical RAV = resistance likely | ||||||
| Positions monitored for "Mutations Detected, effects unknown" | ||||||
| 28, 31, 92, 93 | ||||||
| For NGS data: only RASs with >/=2% frequency with be included | ||||||
| EASL 2016 guidelines: NS5a Class RASs, EASL recommends modified Rx | ||||||
| 1. If data are available for the same substitution in both subtypes, use the one indicated with [Use in algorithm] | ||||||
| 2. If data are available in one subtype but not the other, use the avialable data for all subtypes. Adoption of the reference WT amino aicd might be required Adapted WT is indicated in red. | ||||||
| 3. some mutations contain conflicting WT e.g. L28F in GT2b; adaption to ref WT will become F28F. The reporting for this type of mutations is temporarily suspended. | ||||||
| 4. Differential susceptibilities were observed for the same mutations but in different backgrounds (e.g. different isolates of the same subtype, or between 2 different subtypes). The mutation with a higher fold change was chosen to err on the conservative interpretation. |
| 1. Min Gao (2013) Current Opinion in Virol 3:514-520 |
| 2. Daklinza Canadian Product Monogram Sep 8, 2015 |
| 3. EASL Guidelines 2016 |
| 4. Fridell RA, et al. 2011. Journal of virology 85: 7312-20 |
| 5. Zhou (2016) AAC 71(12): 3495 – 3505 |
| 6. FDA NDA Microbiology Virology Reviews_Daklinza_206843Orig1s000MicroR |
Elbasvir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
|---|---|---|---|---|---|---|
| WT (2a_JFH_L31) [Use in algorithm] | ||||||
| WT (2a_J6_M31) [Conflicting WT] | ||||||
| WT (GT2b_MD2b_L31) [Conflicting WT] | ||||||
| T24A (GT2b) [Not used in algorithm] | ||||||
| T24T (GT2b) [Not used in algorithm] | ||||||
| T 24Y (GT2b) [Used in algorithm] | ||||||
| T24A | resistance possible | 1 | Clincial VF RAV | |||
| T24P | ||||||
| T24S | resistance possible | 1 | Clincial VF RAV | |||
| L27M | ||||||
| F28C | resistance possible | 1 | Clincial VF RAV | |||
| F28I | ||||||
| F28L | resistance possible | 1 | Clincial VF RAV | |||
| F28S | ||||||
| F28V | ||||||
| L28F (GT2b) [Not used in algorithm] | ||||||
| L 28L (GT2b) [Not used in algorithm] | resistance possible | 1 | Clincial VF RAV | |||
| F 28M (GT2b) [Used in algorithm] | ||||||
| F 28T (GT2b) [Used in algorithm] | ||||||
| L28V (GT2b) [Not used in algorithm] | ||||||
| P29S | ||||||
| K30A | ||||||
| K30E | ||||||
| K30G | ||||||
| K30H | ||||||
| K30M (GT2b) | ||||||
| K30N (GT2b) | ||||||
| K30Q | ||||||
| K30R | ||||||
| K30S | ||||||
| K30T | ||||||
| L 31I (GT2b_MD) [Used in algorithm] | resistance possible | 1 | Clincial VF RAV | |||
| M31I (GT2a_J6) [Not used in algorithm] | ||||||
| L 31M (GT2b_MD) [Used in algorithm] | resistance possible | 1 | Clincial VF RAV | |||
| L 31V (GT2b_MD) [Used in algorithm] | ||||||
| M31V (GT2b) [Not used in algorithm] | ||||||
| S38F (GT2b) | ||||||
| K44R | ||||||
| R44K (GT2b) [Conflicting WT, not used in algorithm] | ||||||
| V52I (GT2b) [Conflicting WT, not used in algorithm] | ||||||
| P58A (GT2a) [Not used in algorithm] | ||||||
| P58A (GT2b) [Used in algorithm] | ||||||
| P58S (GT2b) | resistance possible | 1 | Clincial VF RAV | |||
| P58T | ||||||
| P58Q | ||||||
| N62V | ||||||
| N62S | ||||||
| C92A (GT2b) | ||||||
| C92K | ||||||
| C92N | ||||||
| C92R | ||||||
| C92S (GT 2a) [Not used in algorithm] | ||||||
| C92S (GT2b) [Used in algorithm] | ||||||
| C92T (GT2a) [Not used in algorithm] | ||||||
| C92T (GT2b) [Used in algorithm] | ||||||
| C92Y | ||||||
| Y93C | ||||||
| Y93D | ||||||
| Y93F [Conflicting WT] | ||||||
| Y93F (GT2b) [Use in algorithm] | ||||||
| Y93H | ||||||
| Y93L | ||||||
| Y93N | ||||||
| Y93S | ||||||
| Y93T | ||||||
| T24A+L31M | ||||||
| T24A+C92S | ||||||
| T24S+F28C | ||||||
| T24S+L31M | ||||||
| F28C+ L31M | ||||||
| F28C+L31M | ||||||
| F28L+C92S | ||||||
| F28L+L31I | ||||||
| F28L+L31M | ||||||
| F28S+L31M | ||||||
| F28S+L31I | ||||||
| L28F+M31L (GT2b) | ||||||
| L28F+L31V (GT2b) | ||||||
| P29S+K30G | ||||||
| K30E+C92R | ||||||
| K30Q+C92R | ||||||
| K30R+L31M | ||||||
| L 31I+Y93H (GT2b) [Used in algorithm] | ||||||
| L 31V+Y93H (GT2b) [Used in algorithm] | ||||||
| L31M+P58S | ||||||
| L31M+C92S | ||||||
| T24S+L31M+C92S | ||||||
| F28L+K30R+L31M | ||||||
| F28K+K30R+L31V | ||||||
| F28K+L31M+C92A | ||||||
| F28K+L31M+C92S | ||||||
| F28S+L31M+C92S | ||||||
| F28L+K30R+L31M+C92S | ||||||
| F28L+L31M+C92S |
| 1. Serfaty et al. EASL 2017 http://www.natap.org/2017/EASL/EASL_06.htm |
Ledipasvir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
|---|---|---|---|---|---|---|
| WT (2a_JFH_L31) [Use in algorithm] | 21 | 1x | resistance likely | 1 | LDV has 677x (GT2a) and 8032xFS (GT2b) vs. GT1a | |
| WT (2a_J6_M31) [Conflicting WT] | ||||||
| WT (GT2b_MD2b_L31) [Conflicting WT] | ||||||
| T24A (GT2b) [Not used in algorithm] | ||||||
| T24T (GT2b) [Not used in algorithm] | ||||||
| T 24Y (GT2b) [Used in algorithm] | ||||||
| T24A | ||||||
| T24P | ||||||
| T24S | ||||||
| L27M | ||||||
| F28C | ||||||
| F28I | ||||||
| F28L | ||||||
| F28S | ||||||
| F28V | ||||||
| L28F (GT2b) [Not used in algorithm] | ||||||
| L 28L (GT2b) [Not used in algorithm] | ||||||
| F 28M (GT2b) [Used in algorithm] | ||||||
| F 28T (GT2b) [Used in algorithm] | ||||||
| L28V (GT2b) [Not used in algorithm] | ||||||
| P29S | ||||||
| K30A | ||||||
| K30E | ||||||
| K30G | ||||||
| K30H | ||||||
| K30M (GT2b) | ||||||
| K30N (GT2b) | ||||||
| K30Q | ||||||
| K30R | ||||||
| K30S | ||||||
| K30T | ||||||
| L 31I (GT2b_MD) [Used in algorithm] | ||||||
| M31I (GT2a_J6) [Not used in algorithm] | >44.4 | 2x | likely susceptible | 2 | GT2b | |
| L 31M (GT2b_MD) [Used in algorithm] | 210 | 10x | resistance likely | 1 | ||
| L 31V (GT2b_MD) [Used in algorithm] | ||||||
| M31V (GT2b) [Not used in algorithm] | ||||||
| S38F (GT2b) | ||||||
| K44R | ||||||
| R44K (GT2b) [Conflicting WT, not used in algorithm] | ||||||
| V52I (GT2b) [Conflicting WT, not used in algorithm] | ||||||
| P58A (GT2a) [Not used in algorithm] | ||||||
| P58A (GT2b) [Used in algorithm] | ||||||
| P58S (GT2b) | ||||||
| P58T | ||||||
| P58Q | ||||||
| N62V | ||||||
| N62S | ||||||
| C92A (GT2b) | ||||||
| C92K | ||||||
| C92N | ||||||
| C92R | ||||||
| C92S (GT 2a) [Not used in algorithm] | ||||||
| C92S (GT2b) [Used in algorithm] | ||||||
| C92T (GT2a) [Not used in algorithm] | ||||||
| C92T (GT2b) [Used in algorithm] | ||||||
| C92Y | ||||||
| Y93C | ||||||
| Y93D | ||||||
| Y93F [Conflicting WT] | ||||||
| Y93F (GT2b) [Use in algorithm] | ||||||
| Y93H | 522 | 3 | ||||
| Y93L | ||||||
| Y93N | ||||||
| Y93S | ||||||
| Y93T | ||||||
| T24A+L31M | ||||||
| T24A+C92S | ||||||
| T24S+F28C | ||||||
| T24S+L31M | ||||||
| F28C+ L31M | ||||||
| F28C+L31M | ||||||
| F28L+C92S | ||||||
| F28L+L31I | ||||||
| F28L+L31M | ||||||
| F28S+L31M | ||||||
| F28S+L31I | ||||||
| L28F+M31L (GT2b) | ||||||
| L28F+L31V (GT2b) | ||||||
| P29S+K30G | ||||||
| K30E+C92R | ||||||
| K30Q+C92R | ||||||
| K30R+L31M | ||||||
| L 31I+Y93H (GT2b) [Used in algorithm] | ||||||
| L 31V+Y93H (GT2b) [Used in algorithm] | ||||||
| L31M+P58S | ||||||
| L31M+C92S | ||||||
| T24S+L31M+C92S | ||||||
| F28L+K30R+L31M | ||||||
| F28K+K30R+L31V | ||||||
| F28K+L31M+C92A | ||||||
| F28K+L31M+C92S | ||||||
| F28S+L31M+C92S | ||||||
| F28L+K30R+L31M+C92S | ||||||
| F28L+L31M+C92S |
| 1. Min Gao (2013) Current Opinion in Virol 3:514-520 |
| 2. FDA Microbiology/Virology Reviews Harvoni_Microbiology Reviews_205834Orig1a000MicroR |
| 3. Zhou (2016) AAC 71(12): 3495 – 3505 |
Ombitasvir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
|---|---|---|---|---|---|---|
| WT (2a_JFH_L31) [Use in algorithm] | 0.0008 | 1x | likely susceptible | 1, 2 | ||
| WT (2a_J6_M31) [Conflicting WT] | 0.001 | 1x | likely susceptible | 1 | vs. GT2a_JFH1 | |
| WT (GT2b_MD2b_L31) [Conflicting WT] | 0.004 | 0.4x | likely susceptible | 2 | ||
| T24A (GT2b) [Not used in algorithm] | ||||||
| T24T (GT2b) [Not used in algorithm] | ||||||
| T 24Y (GT2b) [Used in algorithm] | ||||||
| T24A | 0.002 | 15x | resistance possible | 1 | ||
| T24P | ||||||
| T24S | ||||||
| L27M | ||||||
| F28C | ||||||
| F28I | ||||||
| F28L | ||||||
| F28S | unfit | unfit | 1 | |||
| F28V | ||||||
| L28F (GT2b) [Not used in algorithm] | 0.033 | 47x | resistance possible | 1 | L31, L28 in this construct | |
| L 28L (GT2b) [Not used in algorithm] | ||||||
| F 28M (GT2b) [Used in algorithm] | ||||||
| F 28T (GT2b) [Used in algorithm] | ||||||
| L28V (GT2b) [Not used in algorithm] | ||||||
| P29S | ||||||
| K30A | ||||||
| K30E | ||||||
| K30G | ||||||
| K30H | ||||||
| K30M (GT2b) | ||||||
| K30N (GT2b) | ||||||
| K30Q | ||||||
| K30R | ||||||
| K30S | ||||||
| K30T | ||||||
| L 31I (GT2b_MD) [Used in algorithm] | ||||||
| M31I (GT2a_J6) [Not used in algorithm] | ||||||
| L 31M (GT2b_MD) [Used in algorithm] | 0.18 | 247x | resistance likely | |||
| L 31V (GT2b_MD) [Used in algorithm] | 0.361 | 511x | resistance likely | 1 | ||
| M31V (GT2b) [Not used in algorithm] | ||||||
| S38F (GT2b) | ||||||
| K44R | ||||||
| R44K (GT2b) [Conflicting WT, not used in algorithm] | ||||||
| V52I (GT2b) [Conflicting WT, not used in algorithm] | ||||||
| P58A (GT2a) [Not used in algorithm] | ||||||
| P58A (GT2b) [Used in algorithm] | ||||||
| P58S (GT2b) | ||||||
| P58T | ||||||
| P58Q | ||||||
| N62V | ||||||
| N62S | ||||||
| C92A (GT2b) | ||||||
| C92K | ||||||
| C92N | ||||||
| C92R | ||||||
| C92S (GT 2a) [Not used in algorithm] | ||||||
| C92S (GT2b) [Used in algorithm] | ||||||
| C92T (GT2a) [Not used in algorithm] | ||||||
| C92T (GT2b) [Used in algorithm] | ||||||
| C92Y | ||||||
| Y93C | ||||||
| Y93D | ||||||
| Y93F [Conflicting WT] | ||||||
| Y93F (GT2b) [Use in algorithm] | ||||||
| Y93H | resistance possible | In >10% VFs | ||||
| Y93L | ||||||
| Y93N | ||||||
| Y93S | ||||||
| Y93T | ||||||
| T24A+L31M | 0.05 | 15x | likely susceptible | 1 | ||
| T24A+C92S | ||||||
| T24S+F28C | ||||||
| T24S+L31M | ||||||
| F28C+ L31M | ||||||
| F28C+L31M | ||||||
| F28L+C92S | ||||||
| F28L+L31I | ||||||
| F28L+L31M | 0.176 | 247x | resistance likely | 1 | this is more JFH-L31M like. JFH=F28 | |
| F28S+L31M | 4710x | resistance likely | 1 | in GT2b with 31M | ||
| F28S+L31I | ||||||
| L28F+M31L (GT2b) | ||||||
| L28F+L31V (GT2b) | ||||||
| P29S+K30G | ||||||
| K30E+C92R | ||||||
| K30Q+C92R | ||||||
| K30R+L31M | ||||||
| L 31I+Y93H (GT2b) [Used in algorithm] | ||||||
| L 31V+Y93H (GT2b) [Used in algorithm] | ||||||
| L31M+P58S | ||||||
| L31M+C92S | ||||||
| T24S+L31M+C92S | ||||||
| F28L+K30R+L31M | ||||||
| F28K+K30R+L31V | ||||||
| F28K+L31M+C92A | ||||||
| F28K+L31M+C92S | ||||||
| F28S+L31M+C92S | ||||||
| F28L+K30R+L31M+C92S | ||||||
| F28L+L31M+C92S | ||||||
| 1. Krishnan et al., (2015) AAC 59:979-987 |
| 2. Viekira Pak US Product Label |
Pibrentasvir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Reference | Comments |
|---|---|---|---|---|---|---|
| WT (2a_JFH_L31) [Use in algorithm] | 0.0005 | 1x | likely susceptible | 1,2,3 | 6xGT2a isolates, 2b (0.001 - 0.002, n=11) | |
| WT (2a_J6_M31) [Conflicting WT] | 0.0023 | 1x | likely susceptible | 1 | pt isolates: 0.001-0.002 | |
| WT (GT2b_MD2b_L31) [Conflicting WT] | 0.0012 | 1x | likely susceptible | 3,1 | 0.0012-0.0019 | |
| T24A (GT2b) [Not used in algorithm] | ||||||
| T24T (GT2b) [Not used in algorithm] | ||||||
| T 24Y (GT2b) [Used in algorithm] | ||||||
| T24A | 0.0013 | 1.3x | likely susceptible | 1,4,3 | ||
| T24P | ||||||
| T24S | 0.001 | 1.1x | likely susceptible | 3 | ||
| L27M | 0.00092 | 0.8x | likely susceptible | 3 | GT2b | |
| F28C | 0.0013 | 1.3x | likely susceptible | 3 | ||
| F28I | ||||||
| F28L | ||||||
| F28S | 0.0012 | 1.2x | likely susceptible | 1,4,3 | ||
| F28V | ||||||
| L28F (GT2b) [Not used in algorithm] | 0.0094 | 0.8-1.1x | likely susceptible | 1,4,3 | GT2b | |
| L 28L (GT2b) [Not used in algorithm] | ||||||
| F 28M (GT2b) [Used in algorithm] | ||||||
| F 28T (GT2b) [Used in algorithm] | ||||||
| L28V (GT2b) [Not used in algorithm] | ||||||
| P29S | ||||||
| K30A | ||||||
| K30E | ||||||
| K30G | 0.00075 | 0.8x | likely susceptible | 1,3 | ||
| K30H | ||||||
| K30M (GT2b) | 0.00012 | 1.2x | likely susceptible | 3 | ||
| K30N (GT2b) | ||||||
| K30Q | ||||||
| K30R | ||||||
| K30S | ||||||
| K30T | ||||||
| L 31I (GT2b_MD) [Used in algorithm] | 0.0018 | 1.5x | likely susceptible | 3,1 | GT2b | |
| M31I (GT2a_J6) [Not used in algorithm] | 0.0012 | 1.2x | likely susceptible | 3,1 | ||
| L 31M (GT2b_MD) [Used in algorithm] | 0.0015 | 1.2x | resistance possible | Yes | 1,2,3 | GT2b. Clinical VF RAS_8 wk tx (3,2) |
| L 31V (GT2b_MD) [Used in algorithm] | 0.0064 | 0.5x | likely susceptible | 1,4 | GT2b | |
| M31V (GT2b) [Not used in algorithm] | ||||||
| S38F (GT2b) | ||||||
| K44R | ||||||
| R44K (GT2b) [Conflicting WT, not used in algorithm] | ||||||
| V52I (GT2b) [Conflicting WT, not used in algorithm] | 0.0012 | 1x | likely susceptible | 3 | GT2b | |
| P58A (GT2a) [Not used in algorithm] | ||||||
| P58A (GT2b) [Used in algorithm] | ||||||
| P58S (GT2b) | ||||||
| P58T | ||||||
| P58Q | ||||||
| N62V | ||||||
| N62S | ||||||
| C92A (GT2b) | ||||||
| C92K | ||||||
| C92N | ||||||
| C92R | ||||||
| C92S (GT 2a) [Not used in algorithm] | ||||||
| C92S (GT2b) [Used in algorithm] | 0.0016 | 1.6x | likely susceptible | 3 | ||
| C92T (GT2a) [Not used in algorithm] | ||||||
| C92T (GT2b) [Used in algorithm] | ||||||
| C92Y | 0.00065 | 0.6x | likely susceptible | 3 | GT2b | |
| Y93C | ||||||
| Y93D | ||||||
| Y93F [Conflicting WT] | ||||||
| Y93F (GT2b) [Use in algorithm] | ||||||
| Y93H | not viable | not viable | ||||
| Y93L | ||||||
| Y93N | not viable | not viable | ||||
| Y93S | ||||||
| Y93T | ||||||
| T24A+L31M | 0.0008 | 0.8x | likely susceptible | 3 | ||
| T24A+C92S | 0.0017 | 1.7x | likely susceptible | 3 | ||
| T24S+F28C | 0.0014 | 1.4x | likely susceptible | 3 | ||
| T24S+L31M | ||||||
| F28C+ L31M | ||||||
| F28C+L31M | ||||||
| F28L+C92S | ||||||
| F28L+L31I | ||||||
| F28L+L31M | ||||||
| F28S+L31M | ||||||
| F28S+L31I | 14303 | 14,448x | resistance likely | 3,1 | Original data is F28S+M31L, duplicate results in GT2a and 2b | |
| L28F+M31L (GT2b) | 0.0014 | 1.2x | likely susceptible | 3 | Gt2b | |
| L28F+L31V (GT2b) | not viable | not viable | ||||
| P29S+K30G | 0.0023 | 2.3x | likely susceptible | 1 | ||
| K30E+C92R | ||||||
| K30Q+C92R | ||||||
| K30R+L31M | ||||||
| L 31I+Y93H (GT2b) [Used in algorithm] | ||||||
| L 31V+Y93H (GT2b) [Used in algorithm] | ||||||
| L31M+P58S | ||||||
| L31M+C92S | ||||||
| T24S+L31M+C92S | ||||||
| F28L+K30R+L31M | ||||||
| F28K+K30R+L31V | ||||||
| F28K+L31M+C92A | ||||||
| F28K+L31M+C92S | ||||||
| F28S+L31M+C92S | ||||||
| F28L+K30R+L31M+C92S | ||||||
| F28L+L31M+C92S | 0.002 | 1.6x | likely susceptible | 3 | Gt2b |
| 1. Ng TI, et al. 2017. Antimicrobial agents and chemotherapy 61: e02558-16 |
| 2. Asselah T, et al. 2017. Clinical Gastroenterology and Hepatology https://doi.org/10.1016/j.cgh.2017.09.027 |
| 3. FDA Microbiology Review https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209394Orig1s000MicroR.pdf |
| 4. Ng 2016 EASL http://www.natap.org/2016/EASL/EASL_123.htm |
Velpastasvir
| Mutation | EC50 (nM) | Fold-shift | Phenotype | Clinical RAS | Replciation Fitness (100%) (7) | Reference | Comments |
|---|---|---|---|---|---|---|---|
| WT (2a_JFH_L31) [Use in algorithm] | 0.009 | 1x | likely susceptible | 100 | 1,2 | ||
| WT (2a_J6_M31) [Conflicting WT] | 0.005-0.016 | 1.5x | likely susceptible | 1,4 | vs. JFH-1 | ||
| WT (GT2b_MD2b_L31) [Conflicting WT] | 0.002-0.006 | 1x | likely susceptible | 1,4 | |||
| T24A (GT2b) [Not used in algorithm] | <2.5x | likely susceptible | 7 | GT2b | |||
| T24T (GT2b) [Not used in algorithm] | <2.5x | likely susceptible | 7 | GT2b | |||
| T 24Y (GT2b) [Used in algorithm] | <2.5x | likely susceptible | 7 | GT2b | |||
| T24A | 0.5x | likely susceptible | 68 | 7 | |||
| T24P | <2.5x | likely susceptible | 7 | ||||
| T24S | <2.5x | likely susceptible | 7 | VEL RAS (5) | |||
| L27M | |||||||
| F28C | <2.5x | Resistance possible | Yes | 7,6 | clincial TE RAV, 4% (6) | ||
| F28I | |||||||
| F28L | 0.1x | likely susceptible | 153 | 7 | |||
| F28S | 91x | resistance likely | 30 | 2,6,7 | |||
| F28V | <2.5x | likely susceptible | 7 | ||||
| L28F (GT2b) [Not used in algorithm] | 2.5 - 100x | Resistance possible | 5 | ||||
| L 28L (GT2b) [Not used in algorithm] | |||||||
| F 28M (GT2b) [Used in algorithm] | |||||||
| F 28T (GT2b) [Used in algorithm] | |||||||
| L28V (GT2b) [Not used in algorithm] | <2.5x | likely susceptible | 7 | ||||
| P29S | |||||||
| K30A | <2.5x | likely susceptible | 7 | ||||
| K30E | |||||||
| K30G | |||||||
| K30H | <2.5x | likely susceptible | 7 | ||||
| K30M (GT2b) | <2.5x | likely susceptible | 7 | GT2b | |||
| K30N (GT2b) | <2.5x | likely susceptible | 7 | GT2b | |||
| K30Q | <2.5x | likely susceptible | 7 | ||||
| K30R | <2.5x | likely susceptible | 7 | ||||
| K30S | <2.5x | likely susceptible | 7 | ||||
| K30T | <2.5x | likely susceptible | 7 | ||||
| L 31I (GT2b_MD) [Used in algorithm] | Resistance possible | Yes | 3 | Clinical TE RAV (3) | |||
| M31I (GT2a_J6) [Not used in algorithm] | 0.005 | 0.6x | likely susceptible | 1,7 | M31L (GT2a_J6). GT2b_M31L <2.5x (7) | ||
| L 31M (GT2b_MD) [Used in algorithm] | 0.009 | 2x | Resistance possible | Yes | 130 | 3,1,5,7 | Clinical TE RAV (3) in GT2b_MD. EC50 for GT2b_MD_L31M=0.004 (2xFC) |
| L 31V (GT2b_MD) [Used in algorithm] | 10x | resistance likely | Yes | 3,4,5,6 | Clinical TE RAV (3,6) | ||
| M31V (GT2b) [Not used in algorithm] | <2.5x | likely susceptible | 7 | ||||
| S38F (GT2b) | <2.5x | likely susceptible | 7 | GT2b | |||
| K44R | 0.005 | 0.6x | likely susceptible | 1 | vs. J6 | ||
| R44K (GT2b) [Conflicting WT, not used in algorithm] | 0.011 | 2.75 | Resistance possible | vs. MD2b | |||
| V52I (GT2b) [Conflicting WT, not used in algorithm] | |||||||
| P58A (GT2a) [Not used in algorithm] | <2.5x | likely susceptible | 7 | ||||
| P58A (GT2b) [Used in algorithm] | 2.5 - 100x | Resistance possible | 7 | ||||
| P58S (GT2b) | 0.01 | 2.5x | likely susceptible | 1 | vs. MD2b | ||
| P58T | <2.5x | likely susceptible | 7 | ||||
| P58Q | 6 | clinical TE RAV, 1% (6) | |||||
| N62V | 0.01 | 1.1x | likely susceptible | 1 | |||
| N62S | 0.003 | 0.3x | likely susceptible | 1 | |||
| C92A (GT2b) | <2.5x | likely susceptible | 7 | GT2b | |||
| C92K | <2.5x | likely susceptible | 7 | ||||
| C92N | <2.5x | likely susceptible | 7 | ||||
| C92R | 4.4x | Resistance possible | 19 | 4,5,7 | |||
| C92S (GT 2a) [Not used in algorithm] | <2.5x | likely susceptible | 7 | ||||
| C92S (GT2b) [Used in algorithm] | 2.5 - 100x | Resistance possible | 7 | ||||
| C92T (GT2a) [Not used in algorithm] | <2.5x | likely susceptible | 7 | ||||
| C92T (GT2b) [Used in algorithm] | >100 | resistance likely | 7 | ||||
| C92Y | |||||||
| Y93C | <2.5x | likely susceptible | 7 | ||||
| Y93D | unfit | 0.1 | 7 | ||||
| Y93F [Conflicting WT] | <2.5x | likely susceptible | 7 | ||||
| Y93F (GT2b) [Use in algorithm] | 2.5 -100x | Resistance possible | 7 | ||||
| Y93H | 46x | resistance likely | Yes | 53 | 2,3,5,6,7 | Clinical TE RAV (3,6) | |
| Y93L | <2.5x | likely susceptible | 7 | ||||
| Y93N | >100x | resistance likely | Yes | 4,5,6 | GT2b, clinical TE RAV, 1% (6) | ||
| Y93S | <2.5x | likely susceptible | 7 | ||||
| Y93T | <2.5x | likely susceptible | 7 | ||||
| T24A+L31M | |||||||
| T24A+C92S | |||||||
| T24S+F28C | |||||||
| T24S+L31M | |||||||
| F28C+ L31M | |||||||
| F28C+L31M | |||||||
| F28L+C92S | |||||||
| F28L+L31I | |||||||
| F28L+L31M | |||||||
| F28S+L31M | |||||||
| F28S+L31I | |||||||
| L28F+M31L (GT2b) | |||||||
| L28F+L31V (GT2b) | |||||||
| P29S+K30G | |||||||
| K30E+C92R | |||||||
| K30Q+C92R | |||||||
| K30R+L31M | |||||||
| L 31I+Y93H (GT2b) [Used in algorithm] | <2.5x | likely susceptible | 7 | ||||
| L 31V+Y93H (GT2b) [Used in algorithm] | >100x | resistance likely | 7 | GT2b | |||
| L31M+P58S | 2.5-100x | Resistance possible | 7 | ||||
| L31M+C92S | |||||||
| T24S+L31M+C92S | |||||||
| F28L+K30R+L31M | |||||||
| F28K+K30R+L31V | |||||||
| F28K+L31M+C92A | |||||||
| F28K+L31M+C92S | |||||||
| F28S+L31M+C92S | |||||||
| F28L+K30R+L31M+C92S | |||||||
| F28L+L31M+C92S |
| 1 Cheng G et al. Journal of Hepatology 2013;58:S484-S5. | ||
| 2. Epclusa US Product Label. July 2016 | ||
| 3. Lawitz (2016) AAC 60(9):5368-5378. doi:10.1128/AAC.00763-16. (Monotherapy) | ||
| 4. Epclusa Canadian Product Label July 8, 2016 | ||
| 5. Sarrazin C, et al. 2017. Gastroenterology 152: S1062 | ||
| 6. FDA Microbiology/Virology Reviews VoseviMicrobiology Reviews_2091950Orig1a000MicroR | ||
| 7.FDA Microbiology/Virology Reviews Epclusa_ 208341Orig1s000 (2015) |