Table 3.
GT and subject | Baseline RAM | Clonal NS5A variant(s) at day 4 (frequency)a | GS-5885 EC50 (nM)b |
Daclatasvir EC50 (nM)b |
||||
---|---|---|---|---|---|---|---|---|
Baseline | Day 4 | Fold change | Baseline | Day 4 | Fold change | |||
1a | ||||||||
O | WT (10%), M28T (3%), Q30H (23%), Q30R (53%), L31M (3%), Y93C (7%) | 0.002 | 0.071 | 35.5 | 0.008 | >1.5 | >196 | |
I | WT (44%), Q30R (31%), L31M (25%) | 0.005 | 0.403 | 88 | 0.007 | 2.07 | 292 | |
BJ | Q30H (3%), Q30R (67%), Q30E (3%), H58D (3%), Y93C (7%), Y93H (7%), Q30R+Y93C (10%) | 0.017 | 4.3 | 355.6 | 0.003 | 0.8 | 267 | |
L | WT (13%), M28T (7%), Q30H (7%), Q30R (7%), L31M (33%), Y93C (3%), Q30R+Y93C (10%) | 0.004 | >1.5 | >375 | 0.005 | >1.5 | >288 | |
BR | Q30R (86%), L31M (4%), H58D (11%) | 0.009 | 3.5 | 389 | 0.007 | 2.1 | 300 | |
T | WT (3%), Q30R (40%), L31M (3%), H58D (47%), Q30R+H58D (7%) | 0.006 | 0.52 | 87 | 0.003 | 0.49 | 163 | |
BI | Q30R (87%), Q30E (3%), K24R+Q30R (10%) | 0.006 | >50 | >8,333 | 0.006 | 22.2 | 3700 | |
BK | Q30K (7%), Q30R (66%), Y93C (14%), Y93H (7%), Q30R+Y93H (3%), Q30R+Y93C (3%) | 0.004 | >50 | >12,500 | 0.004 | >50 | >12,500 | |
Q | 12% Y93C | M28T (3%), Q30R (26%), L31M (7%), Y93C (52%), M28V+Q30R (3%), M28T+Y93C (7%), Q30R+Y93C (3%) | 0.014 | 0.285 | 20.4 | 0.057 | 0.487 | 8.5 |
1b | ||||||||
AR | Y93Hc | 0.001 | 0.994 | 994 | 0.013 | 0.12 | 9.6 |
Clonal variants were determined by deep sequencing.
Fold change in the EC50 was calculated by dividing the day 4 EC50 by the baseline EC50.
Genotype 1b sample, day 14 population sequencing EC50.