Hepatitis C virus NS5A inhibitors and drug resistance mutations

Table 2 Resistance profiles of hepatitis C virus NS5A inhibitors in hepatitis C virus genotype 1- and 2-infected patients[61,66,73-75]

HCV NS5A inhibitor	Mean maximal viral decline (log IU/mL)	Maximal viral decline in patients with RAVs at baseline (log IU/mL)
HCV genotype 1a-infected
DCV	3.8 (60 mg, 14 d)	Q30R (10%)	2.9
LDV	3.1-3.3 (10-90 mg, 3 d)	Q30E/Q	0.88
		L31M	0.16
		Y93C (12%)	1.6
PPI-668	3.3 (80-160 mg, 3 d)	M28V (50%)	3.7
		M28T (7%)	2.8
		M28T (10%)/L31M (11%)	3.6
		H58D (69%)/N (31%)	2.2
IDX719	3.2-3.6 (25-100 mg, 3 d)	M28M/V	3.6
ACH-3102	3.5-3.9 (50-300 mg, single dose)	M28V, T (2%-24%)	3.4 to 4
		L31M (28%)	3.4
		Y93C, D, H (2%-3%)	4 to 4.6
HCV genotype 1b-infected
DCV	4.3 (10 mg, 14 d)	Q54H, N	> 4
		Q54H/Y93H	> 4
LDV	3.3 (10 mg, 3 d)	L31M	2.09
PPI-668	2.9 (40 mg, 3 d; only 1 patient)	R30Q	2.9
	3.8-4 (80-240 mg, 3 d)	L31M	4
		P58S	3.8
		L28M (7%), R30Q (76%), L31M (20%)	3.5
		R30Q/L31I/Y93H	0.33
IDX-719	3-4.3 (25-50 mg, 3 d)	R30Q/Y93H	2.8
HCV genotype 2a-infected
PPI-668	0.33 (160 mg, 3 d; only 1 patient)	F28L/A30K/L31M	0.33
IDX-719	2.0 (50-100 mg, 3 d)	L31M	0.45
		L31L/M	0.85
HCV genotype 2b-infected
PPI-668	3.0 (160 mg, 3 d)	A30K	0.48
		Y93H (7%)	0.45
		Y93H	0.25

DCV: Daclatasvir; LDV: Ledipasvir; RAVs: Resistance-associated variants; HCV: Hepatitis C virus.