TABLE 4.

Genotypic and phenotypic analysis of GT1a patient viral isolates^a

Dose (mg)	GT or patient	Nadir (h)	NS5A RAM(s) at baseline, first 100 aa (%)	NS5A RAM(s) at nadir, first 100 aa (%)	EDP-239 EC50 (nM)c
					Baseline	Nadir	Fold change
	GT1a (H77)			Reference	0.006
10	5306	24	M28V(2)	K24R(2), M/V28T(40)/V(3), Q30H(2)/R(30), L31M(7), F36L(49), H58D(3)/L(2), A92T(1), Y93C(2)/H(8)	0.005	17.0	3,400
	5310	24	K24R(2), M28V(2)	K24R(2), M/V28T(7)/V(5), Q30H(5)/R(45), L31M(8), H58D(2), A92T(3), Y93C(7)/H(12)/N(1)	0.006	0.29	48
	5314	24	K24R(4), Q30H(44)	Q30H(99)	0.004	7.4	1,850
	5407	24	M28V(23), H58R(2), Y93F(28)	M28V(72), Q30H(4)/R(80), L31M(2), H/R58C(19)/D(8), Y93F(13)	0.002	>5	>2,500
30	5303b	48		M28T(17)/V(5), Q30E(2)/H(3)/R(57), H58D(6), Y93C(4)/H(3)	0.010	0.043	4
	5307	48		M28T(22), Q30H(7)/R(31), L31V(7), H58D(7), Y93C(7)/H(14)	0.010	1.7	170
	5313	24	Q30R(4)	M28T(6), Q/R30H(9)/R(87)	0.004	0.40	100
100	5301	48		Q30R(94), Y93H(6)	0.007	5.6	800
	5308	48	M28V(2)	M/V28T(12)/V(10), Q30R(64), Y93C(25)	0.006	4.7	783
	5311	24		M28T(9), Q30R(46)	0.011	0.009	1
200	5304	48	M28V(29)	M/V28A(2)/V(64), Q30E(4)/R(46), Y93C(8)/H(34)/S(3)	0.008	76.2	9,525
	5305	24	K24N(3)/R(3)/S (1), M28T(90), Q30H(56)/L(2), Q30R(13), F36L(99), H58D(1)/R(1)	K24N(2), F36L(99), M28T(94), Q/H30H(78)/E(4)/R(16)	776.3	222.4	0.3
	5309	24	M28V(43), E62V(25)	M28V(63), Q30E(3)/R(58), H58D(7), Y93H(7)/N(10)	0.008	5.5	688

^aaa, amino acids.

^bSequencing of baseline sample failed; 2-h time point used for comparison.

^cn = 3 independent experiments.