TABLE 7.
In vitro activity of pibrentasvir against amino acid substitutions observed in DAA-experienced HCV GT1b-infected patients
| NS5A amino acid substitution(s)a | Mean pibrentasvir EC50 ± SD (pM) | Fold change in EC50 |
|---|---|---|
| GT1b wild type | 1.9 ± 0.80 | |
| Q24K | 3.0 ± 0.59 | 1.6 |
| L28M | 1.8 ± 0.11 | 1.0 |
| L28T | 1.7 ± 0.44 | 0.9 |
| R30Q | 0.88 ± 0.49 | 0.5 |
| L31F | 2.3 ± 0.37 | 1.2 |
| L31M | 2.9 ± 1.2 | 1.5 |
| L31V | 1.5 ± 0.43 | 0.8 |
| P32deletion | 1,968 ± 203 | 1,036 |
| P58S | 2.4 ± 1.3 | 1.2 |
| A92E | 0.92 ± 0.23 | 0.5 |
| A92V | 0.86 ± 0.15 | 0.5 |
| Y93H | 1.1 ± 0.27 | 0.6 |
| Y93S | 0.74 ± 0.24 | 0.4 |
| Q24K + R30Q | 3.0 ± 0.21 | 1.6 |
| L28M + R30Q | 0.79 ± 0.10 | 0.4 |
| L28M + Y93H | 2.2 ± 0.23 | 1.2 |
| R30Q + Y93H | 2.3 ± 0.15 | 1.2 |
| L31F + P32deletion | 38,877 ± 1,227 | 20,461 |
| L31F + A92E | 1.2 ± 0.15 | 0.6 |
| L31F + Y93H | 2.8 ± 0.17 | 1.5 |
| L31M + Y93H | 1.3 ± 0.24 | 0.7 |
| L31V + A92K | 5.0 ± 0.62 | 2.6 |
| L31V + Y93H | 1.7 ± 0.31 | 0.9 |
| P58S + Y93H | 1.5 ± 0.45 | 0.8 |
| L28M + R30Q + Y93H | 1.0 ± 0.24 | 0.5 |
a
Amino acid substitutions that were detected at baseline or at the time of failure in patients experiencing virologic failure are underlined.