Effect of the baseline Y93H resistance-associated substitution in HCV genotype 3 for direct-acting antiviral treatment: real-life experience from a multicenter study in Sweden and Norway

Figures & data

Figure 1. Flowchart of patients included in the study. Baseline resistance testing in the control group was performed retrospectively.

Table 1. Genotype 3 patient baseline characteristics.

	Intervention group (n = 130)	Control group (n = 78)	p Value
Median age, yr. (range)	55 (22–77)	52 (25–67)
Male, n (%)	95 (73.1)	52 (66.7)	.33
Cirrhosis, n (%)	49 (37.7)	48 (61.5)	.00085
Median HCV RNA, log10 IU/ml (range)	6.1 (3.2–7.9)	6.0 (4.3–7.2)
Beseline Y93H (%)	5 (3.8)	4 (5.1)	.66
Baseline A30K (%)	5 (3.8)	2 (2.6)	.62
Previous HCV treatment^a, n (%)
Treatment- naïve	100 (76.9)	46 (59.0)	.0061
Nonresponder	1 (0.8)	4 (5.1)
Partial responder	6 (4.6)	2 (2.6)
Relapse	17 (13.1)	24 (30.8)	.0019
Intolerant	4 (3.1)	1 (1.3)
NA	2 (1.5)	1 (1.3)

^aTreatment referring pegylated interferon (Peg/INF) plus ribavirin.

Table 2. Treatment characteristics of the GT3 patients.

	Intervention group (n = 130)	Control group (n = 78)	p Value
Treatment regime, n (%)
Daclatasvir + sofosbuvir	62 (47.7)	73 (93.6)	1.89E–11
Velpatasvir + sofosbuvir	54 (41.5)	–
Ledipasvir + sofosbuvir	13 (10.0)	5 (6.4)	.37
Sofosbuvir + PEG-INF + ribavirin	1 (0.8)	–
Treatment duration, wk
4 wk^a	1 (0.8)	–
8 wk	1 (0.8)	–
12 wk	100 (76.9)	42 (53.8)	.00054
16 wk	13 (10.0)	8 (10.3)
20 wk	3 (2.3)	–
24 wk	12 (9.2)	28 (35.9)	2.0E–06
Addition of ribavirin, n (%)	50 (38.5)	54 (69.2)	1.73E–05

^aTreatment was discontinued in one patient due to noncompliance.

Table 3. Clinical and treatment characteristics in patients with baseline A30K and Y93H RASs.

Sex	Age	Study Group	Nationality	Metavir score (Child Pugh)	FibroScan (kPa)	Cirrhosis	Treatment	Previous treatment response with PEG-IFN/RBV	Baseline viral load log10(IU/ml)	SVR	Ribavirin	Treatment duration (wk)
Baseline RAS A30K
M	52	C	NO	(A)	NA	Yes	DCV/SOF	N	5.6	No	No	12
M	53	C	SE	NA	NA	Yes	DCV/SOF	N	4.6	Yes	Yes	24
F	54	I	NO	NA	8	No	DCV/SOF	N	6.4	No	No	12
M	65	I	NO	NA	12.4	Yes	VEL/SOF	N	6.2	Yes	Yes	12
M	30	I	NO	4 (A)	16	Yes	VEL/SOF	N	6.8	Yes	Yes	12
M	47	I	NO	NA	11.8	No	VEL/SOF	N	6.7	Yes	Yes	12
M	54	I	NO	NA	10	No	VEL/SOF	N	4.7	Yes	Yes	12
Baseline RAS Y93H
M	49	C	SE	6 (A)	NA	Yes	DCV/SOF	Intolerant	5.0	Yes	Yes	24
F	63	C	SE	5	4.8	No	LED/SOF	NR	5.7	No	Yes	16
M	55	C	SE	4 (B)	NA	Yes	DCV/SOF	N	6.3	No	No	24
F	51	C	SE	(A)	14.3	Yes	DCV/SOF	N	6.3	Yes	Yes	12
F	58	I	NO	3 (A)	NA	Yes	SOF/PEG-IFN	PR	6.1	Yes	Yes	12
M	58	I	NO	NA	11.6	No	VEL/SOF	N	6.5	Yes	Yes	12
M	55	I	NO	NA	6.8	No	VEL/SOF	N	6.9	Yes	Yes	12
M	62	I	SE	NA	1.8	No	LED/SOF	N	5.7	Yes	No	24
M	49	I	SE	A	13.4	Yes	DCV/SOF	N	ND	Yes	No	24

6/7 (85.7%) patients with baseline A30K are from the Norwegian cohort.

3/9 (33.3%) patients with baseline Y93H are from the Norwegian cohort.

Distribution of the cohorts regarding nationality in the intervention and control groups are 57.7% Norwegians versus 42.3% Swedish and 14.1% Norwegians versus 85.9% Swedish, respectively.

Table 4. Clinical characteristics, baseline, and emerging NS5A RASs in the non-SVR patients.

Sex	Age (yr)	Study group	Cirrhosis	Metavir (Child Pugh score)	Fibro Scan (kPa)	Treatment	Previous treatment response with PEG-IFN/ RBV	Baseline viral load, log10 (IU/ml)	Baseline RAS(s)	RAS(s) at relapse	Ribavirin	Treatment time (wk)
M	52	C	Yes	A	NA	DCV/SOF	N	5.6	A30K	ND	No	12
M	53	C	Yes	5(A)	NA	DCV/SOF	N	5.9	0	Y93H	No	16
M	63	C	Yes	5(A)	NA	DCV/SOF	RR	6.2	0	Y93H	Yes	12
M	56	C	Yes	6	39.7	DCV/SOF	N	5.8	0	NA	Yes	24
M	53	C	Yes	9	NA	DCV/SOF	N	6.3	0	Y93H	Yes	24
F	63	C	No	5	4.8	LED/SOF	N	5.7	Y93H	Y93H	Yes	16
M	55	C	Yes	4(B)	NA	DCV/SOF	N	6.3	Y93H	Y93H	No	24
M	53	C	No	NA	9.2	DCV/SOF	NR	6.3	0	Y93H	No	12
M	43	C	Yes	A	23.1	DCV/SOF	RR	6.5	0	Y93H	Yes	12
M	59	I	Yes	3(A)	NA	DCV/SOF	PR	6.7	0	Y93H	Yes	20
F	54	I	No	NA	8.0	DCV/SOF	N	6.4	A30K	A30K	No	12
M	58	I	Yes	A	22.8	DCV/SOF	RR	5.4	0	Y93H	No	12
M	55	I	Yes	A	48.0	LED/SOF	N	7.0	0	0	Yes	NR v16 (Sched.24)
M	60	I	Yes	B	73.0	DCV/SOF	N	5.5	0	Y93H	No	VB v4 (Sched.16)
F	58	I	No	NA	11.1	VEL/SOF	NA	4.6	0	0	No	VB v4 (Sched.12)

C: control group; DCV: Daclatasvir; F: female; I: intervention group; LED: Ledipasvir; M: male; N: naive; ND: not done; NO: Norway; NR: nonresponder; PR: partial responder; RBV: ribavirin; R: relapse; SE: Sweden; SOF: Sofosbuvir; SVR: sustained virologic response; VB: viral breakthrough; VEL: Velpatasvir.

Figure 2. Sustained virologic response rates (SVR) in the intervention and control groups. Treatment period for the intervention group was from 2 October 2014 to 5 December 2017, and for the control group from 10 April 2014 to 17 November 2016. SVR rates in the intervention group (blue bars) and the control group (orange bars).