Table 6.

In vitro enzyme and replicon susceptibility analysis of HCV NS3 protease sequences derived from patients in the single-ascending-dose study

Patient	Genotype	Dose (mg)	Isolate time point	Log10 HCV RNA (IU/ml)	Polymorphism(s)a	Fold change (vs. reference) in:
						ASV IC50b	ASV EC50c
1	1a	200	Baseline	6.3	Q80K	1	3
			24 h	5.9	Q80K
2	1b	200	Baseline	6.9	V170V/I	1	1
			24 h	3.9	V170V/I
3	1a	200	Baseline	7.2	Q80K	1
			24 h	5.7	Q80K
4	1a	200	Baseline	6.9	Q80K	1
			24 h	6.1	Q80K
5	1b	200	Baseline	6.0	S7A, I72T, S122S/T	1	1
			24 hd	3.2	S7, L14F, S42T, I72 S122, V132I, V170V/I	1	1
			48 h	3.0	S7, L14F, I72, S122 V132I, C145Y, V170I	1	0.4
			144 h	4.4	S7, L14F, S122	1
6	1b	600	Baseline	6.3		1
			24 h	3.8
7	1a	600	Baseline	7.2	Q80K	1
			24 h	5.6	Q80K
8	1a	600	Baseline	6.8		1	2
			24 h	4.1
9	1a	600	Baseline	6.3	Q80K	1
			24 h	4.3	Q80K
10	1a	600	Baseline	6.6	S122S/G	1
			24 h	3.3	S122, V55A, Q80K	1
			48 hd	2.9	S122, V55A	1
			48 hd		S122, V55A, Q80K	1
			144 h	5.3	S122	1

^aOnly polymorphisms at NS3 amino acid positions reported to confer resistance to protease inhibitors are shown for patients where no changes from baseline were detected over 144 h. These positions included 36, 43, 54, 55, 77, 78, 79, 80, 107, 122, 132, 155, 156, 158, 168, 170, and 175.

^bRecombinant NS3/4A protease assay; the genotype 1a NS3/4A protease reference sequence was H77c; genotype 1b NS3/4A protease reference sequence was Con1. ASV, asunaprevir.

^cReplicon assay; the genotype 1a replicon reference sequence was H77c; genotype 1b replicon reference sequence was Con1.

^dTo assess assay variability and primer sequence bias, protein was expressed from amplicons generated from different primer sets.