Real-world efficacy of daclatasvir and asunaprevir with respect to resistance-associated substitutions

Table 1 Baseline patient characteristics

No. of patients	n = 392
Gender (male/female)	159/233
Age, yr	71.0	(64.0-77.0)
< 65 yr vs ≥ 65 yr	99/293
Laboratory data
Level of viremia (log IU/mL)	6.2	(5.8-6.5)
< 6.0 vs ≥ 6.0	137 vs 255	(35.1% vs 64.9%)
Platelet count (× 104/mm3)	12.6	(9.2-16.7)
10 < vs ≥ 10	114/278	(29.0% vs 70.4%)
ALT (IU/L)	41	(29-65)
γ-GTP(IU/L)	34	(22-57)
Other data
Prior treatment
IFN vs PEG plus RBV vs TVR vs SMV	70/147/13/9
NS5A polymorphisms, n (%)
L31 substitution, n = 288	10 (3.5)
Y93 substitution, n = 321	27 (8.4)
L31 and/or Y93, n = 321	35 (10.9)

Data are presented as numbers. Percentages or medians with interquartile ranges are presented in parentheses. ALT: Alanine aminotransferase; γ-GTP: Gamma-glutamyltransferase; IFN: Interferon; PEG plus RBV: Pegylated interferon plus ribavirin; TVR: Pegylated interferon plus ribavirin plus telaprevir triple therapy; SMV: Pegylated interferon plus ribavirin plus simeprevir triple therapy; L31: NS5A: L31 substitution patients. A total of 288 patients were assessed at pretreatment; Y93: NS5A:Y93 substitutions. A total of 321 patients were assessed at pretreatment.

Table 2 Pretreatment and post-treatment major RAVs of 17 patients who did not achieve SVR12 (NS3:D168, NS5A:L31, and Y93 substitution)

No.	Pretreatment						Post-treatment
	C.C.	D168	L31	Y93	Other NS3	Other NS5A	D168	L31	Y93	Other NS3	Other NS5A
1	BT	E	-	-	-	-	E	-	-	-	R30H
2	REL	-	L/I	-	-	A92T	-	M	-	-	A92K
3	NR	-	-	H	V170I	Q54Y	-	I	H	V170I	Q54Y
4	BT	Y	-	-	-	Q54H	Y	F	H	-	Q54H
5	NR	E	-	-	Q80R, V170I	Q54H	E	V	H	Q80R, V170I	Q54H
6	BT	E	-	-	-	Q54H	E	V/M	H	V170I	Q54H
7	BT	-	M/L	-	-	Q54V	V	M/V	H	-	Q54V
8	BT	-	-	H	-	Q54H	V	M	H	-	Q54H
9	REL	-	-	H	-	Q62E	V	I	H	-	Q62E
10	BT	-	-	H/Y	-	-	T	M	H	-	-
11	BT	-	-	H/Y	-	-	V	V/F	H	V170I	-
12	BT	Y	F	H	-	-	D	F	H	-	Q54H
13	BT	-	-	-	-	Q54H, A92T	V	-	-	-	Q54H, A92K
14	REL	-	-	-	-	Q54H	E	-	-	-	P32L, Q54H, A92K
15	BT	-	-	-	-	Q62N	V	V	H	-	Q62N
16	BT	-	-	-	-	-	-	V	H	-	-
17	REL	-	-	-	-	-	E	M	H	-	-

C.C.: Virological clinical course; NR: Non-response, HCV RNA was still detectable during treatment so treatment was discontinued; BT: Breakthrough, HCV RNA became undetectable but reappeared during treatment; REL: Relapse, HCV was undetectable at the end of the 24-wk treatment but became quantifiable again during follow-up; D168: NS3:D168 substitution; L31: NS5A:L31 substitution; Y93: NS5A:Y93 substitutions. Other NS3, other NS3 substitution except D168 substitution; Other NS5A, other NS5A substitution except L31 and Y93 substitution. Analyses were performed by using a direct-sequencing method.