Table 2.
Frequency and spectrum of resistance-associated mutations in all subjects receiving active drug at day 4
| NS5A mutation(s) | No. of subjects with GS-5885 RAMs at day 4 by cohort and dosea |
|||||
|---|---|---|---|---|---|---|
| GT1a |
GT1b (10 mg [n = 6]) | |||||
| 1 mg (n = 10) | 3 mg (n = 10) | 10 mg (n = 8) | 30 mg (n = 8) | 90 mg (n = 9) | ||
| K24E/K | 1 (−2.6) | |||||
| A25A/T | 1 (−0.7) | |||||
| M28M/T | 1 (−3.4) | |||||
| Q30Q/R | 1 (−3.2) | 1 (−2.9) | 1 (−3.6) | 2 (−3.7, −2.7) | ||
| Q30H/Q/R | 3 (−3.1 to −3.3) | 1 (−3.2) | ||||
| E/Q30E | 1 (−0.9)c | |||||
| L31M | 2 (−1.5, −3.0)b | |||||
| L31L/M | 1 (−3.2) | 1 (−2.2) | ||||
| Y93C | 1 (−1.6) | |||||
| Y93H | 2 (−2.3, −3.2) | |||||
| Y93H/Y | 1 (−3.1) | 1 (−3.5) | ||||
| K24K/N, Q30H/Q/R | 1 (−3.0) | |||||
| K24K/R, Q30Q/R | 1 (−3.7) | |||||
| K/R24R, L31L/M | 1 (−2.6) | |||||
| M28M/T, Q30Q/R | 1 (−3.0) | |||||
| Q30Q/R, L31L/M | 1 (−3.1) | |||||
| Q30H/Q, A92A/V | 1 (−3.7) | |||||
| Q30Q/R, H58D/H | 1 (−3.6) | |||||
| Q30Q/R, Y93C/Y | 1 (−3.3) | 2 (−3.6, −3.0) | ||||
| Q30K/Q/R, Y93C/H/R/Y | 1 (−3.6) | |||||
| Q30E/G/Q/R, L31L/M | 1 (−3.3) | |||||
| L31M, Y93H | 1 (−2.4) | |||||
| L31L/M, H58H/P | 1 (−2.8) | |||||
| L31L/M, Y93C/Y | 1 (−3.3) | |||||
| L31L/M, Y93H/Y | 1 (−2.7) | |||||
| P/S58P, Y93H | 1 (−4.1) | |||||
| E/Q62E, Y93H | 1 (−3.8) | |||||
| M28M/T, Q30Q/R, L31L/M | 1 (−3.2) | |||||
| M28M/V, Q30Q/R, Y93C/Y | 1 (−2.9) | |||||
| L31M, H/P58P, D/E62D | 1 (−2.4) | |||||
| Q30Q/R, L31L/M, Y93C/Y | 1 (−3.7) | |||||
| Total (% of group) | 3 (30) | 10 (100) | 8 (100) | 8 (100) | 9 (100) | 6 (100) |
a
Change from baseline as determined by population sequencing. For each cohort, n is the number of subjects with available sequence data at day 4. The absence of data indicates that the mutation(s) was not detected. Except as noted, values in parentheses represent the maximum log10 change in HCV RNA.
b
One of these two subjects harbored L31M at baseline and on day 4.
c
Harbored Q30E/Q at baseline.