Table 4.
Fold Change in EC50s With RAS Y93H for Approved NS5A Inhibitors
| NS5A Inhibitor | Fold-change in vitro1 | ||||
|---|---|---|---|---|---|
| GT1a | GT1b | GT2 | GT3 | GT4 | |
| Daclatasvir | 1400–5432 | 12–145 | 749–1750 | 2154–3733 | 45–169 |
| Elbasvir | 220–600 | 12-67 | ND | 157 | 7.5 |
| Ledipasvir | 1677–3309 | 1319–1807 | ND | 30 | 1000 |
| Ombitasvir | 41,383 | 77 | 4710 | 6728 | 20–100 |
| Pibrentasvir | 7 | 0.6 | ND | 2.5 | ND |
| Velpatasvir | 609 | 3 | 46 | 724 | 3 |
Note: data are according to ref 80
Y93H fold change value in comparison with wild-type strains; maximum and minimum values are reported.
For first-generation NS5A-inhibitors, RASs with more than 100-fold changes are shown in red (resistance likely); RASs with 20–100-fold changes are reported in blue (resistance possible); RASs with 3–20-fold changes are reported in green (likely susceptible). For second-generation NS5A-inhibitors, such as elbasvir and velpatasvir, RASs with more than 10-fold chnages are reported in red (resistance likely); RASs with 3–9-fold changes are reported in blue (resistance possible); RASs with less than 2.5-fold changes are reported in green (likely susceptible);
GT, genotype; ND, no data available; EC50, effective concentration for 50% inhibition