TABLE 6.
Genotypes and phenotypes of virus in serum samples of HCV genotype 1a-infected chimpanzee before and after treatment with A-837093
| Day | Genotype | No. of sequences/total no. (%) | EC50 (nM [fold reduction])
|
|
|---|---|---|---|---|
| A-837093a | BILN 2061 | |||
| 0 | WTb | 27/27 (100) | 3.5 | 3.1 |
| 2 | G554S | 2/20 (10) | 7.7 (2.2) | 2.7 (0.9) |
| WT | 18/20 (90) | |||
| 5 | G554D | 2/19 (11) | 4.5 (1.3) | 3.1 (1) |
| D559G | 2/19 (11) | |||
| D559N | 1/19 (5) | |||
| WT | 14/19 (74) | |||
| 16 | G554D | 6/33 (18) | 13.8 (3.9) | 2.8 (0.9) |
| G554S | 2/33 (6) | |||
| D559G | 8/33 (24) | |||
| D559N | 2/33 (6) | |||
| G554D + D559G | 1/33 (3) | |||
| WT | 14/33 (42) | |||
| 28 | Y448C | 1/20 (5) | 8.2 (2.3) | 3.3 (1.1) |
| Y448H | 3/20 (15) | |||
| G554D | 2/20 (10) | |||
| WT | 14/20 (70) | |||
a
Inhibition curves for A-837093 were biphasic, indicating a mixed population of sensitive and highly resistant variants. EC50 values are those for the predominant, sensitive population.
b
WT = Y448, G554, and D559.