Naturally occurring resistance mutations to inhibitors of HCV NS5A region and NS5B polymerase in DAA treatment-naïve patients

Table 3 Amino acid mutations in the HCV NS5A protein in DAA-naïve patients infected with HCV genotypes 1a (n = 32) or 1b (n = 30)

DAAs	NS5A mutations in DAA-naïve patients
DAAs	Genotype 1a	Fold change in EC50	Genotype 1b	Fold change in EC50	References
Daclatasvir	M28V (1/32, 3.1%) ^α	1.3	L28M/V (1/30,3.3%)	2.0	[15, 17, 19]
	Q30E/H/R/K		R30H
Daclatasvir	L31M/(1/32, 3.1%)	341	L31M (2/30, 6.6%)	3	[15, 17, 19]
Ledipasvir	L31M/(1/32, 3.1%)	140	L31M		[29]
GSK805	L31M/(1/32, 3.1%)	>150	L31M		[30]
Samatasvir	L31M		L31M (2/30, 6.6%)	3.6	[31]
	P32L		P32L
Daclatasvir	Q54H/L/N		Q54H (8/30, 26.6%)	1.0	[19]
Daclatasvir	H58P (2/32, 6.2%)	1.2	P58S/T/L		[19]
	N69T		N69T
	A92V		A92V
Daclatasvir	Y93C/H/N		Y93H (3/30, 10%)	24	[15, 17, 19]
Ledipasvir	Y93C/H/N		Y93H (3/30, 10%)	1319	[29]
Samatasvir	Y93C/H/N		Y93H (3/30, 10%)	93	[31]
	V153M		V153M
	R157W		R157W
	V198A		V198A
	M202L		M202L
	P223S		P223S
	M265V		M265V
GSK805	I280V		I280V (2/30, 6.6%)	<2.0	[30]
	V298A		V298A
	V362A		V362A
	S364P		S364P
	S368P		S368P

^αAmino acid changes conferring resistance to NS5A inhibitors are reported in italics. The number and % of patients with mutated strains is reported in brackets.
GeneBank accession number of NS5A reference sequence for HCV genotype 1a is AF009606, and for genotype 1b, AY045702.

ISSN: 1743-422X