Virology analysis in HCV genotype 1-infected patients treated with the combination of simeprevir and TMC647055/ritonavir, with and without ribavirin, and JNJ-56914845

Vijgen, Leen; Thys, Kim; Vandebosch, An; Van Remoortere, Pieter; Verloes, René; De Meyer, Sandra

doi:10.1186/s12985-017-0760-2

Virology Journal

Table 1 Population sequencing and deep sequencing data for patients with virologic failure

From: Virology analysis in HCV genotype 1-infected patients treated with the combination of simeprevir and TMC647055/ritonavir, with and without ribavirin, and JNJ-56914845

Pt	GT	Reason for failure	Gene	Baseline^a		Time of failure^a		End of study^a
				PS	DS	PS^b	DS	PS^b	DS
Panel 1
1	GT1a	Viral breakthrough	NS3	None	None	D168V	D168F 48.7%	R155K	R155K 7.8%
			NS3	None	None	D168V	D168V 50.4%	R155K	D168E 7.1%
			NS5B	None	None	P495L	P495A 99.3%	P495L	P495L 29.0%
2	GT1a	Viral breakthrough	NS3	None	S122G 1.7%	D168V	Q80R 60.8%	R155K	S122T 2.5%
							R155K 61.6%		R155K 98.9%
							D168V 37.4%
			NS5B	None	None	P495L	P495L 99.5%	None	P495L 13.6%
3	GT1a	Viral breakthrough	NS3	None	NA	Q80R + R155K	NA	R155K	NA
3	GT1a	Viral breakthrough	NS5B	I424V + A499T	NA	I424V + A499T + P495L	NA	I424V + A499T	NA
4	GT1a	Viral breakthrough	NS3	Q80K	Q80K 99.1%	Q80K + R155K	NA	Q80K	Q80K 99.2%
			NS5B	L392F	L392F 99.7%	L392F/L + P495L	NA	L392F	L392F 99.4%
			NS5B	L392F	L392F 99.7%	L392F/L + P495L	NA	L392F	P495L 1.4%
5	GT1a	Viral breakthrough	NS3	Q80K	Q80K 98.6%	Q80K + R155K	NA	Q80K + D168E	Q80K 99.4%
									R155K 74.2%
									D168E 24.6%
			NS5B	V37I	V37I 99.4%	V37I + P495L/S	NA	V37I + P495A	V37I 98.2%
			NS5B	V37I	V37I 99.4%	V37I + P495L/S	NA	V37I + P495A	P495A 32.5%
6	GT1a	Late viral relapse^c	NS3	None	None	D168A	ND	ND	ND
6	GT1a	Late viral relapse^c	NS5B	None	A499T 1.6%	None	ND	ND	ND
Panel 2
7	GT1b	Viral breakthrough	NS3	S122T	S122T 92.8%	S122T + D168V	NA	S122T	S122T 99.1%
7	GT1b	Viral breakthrough	NS5B	None	None	P495L	NA	None	None
8	GT1b	Viral breakthrough	NS3	None	None	D168A/V	D168A 63.6%	None	None
							D168T 2.2%
							D168V 33.3%
			NS5B	None	None	P495L	P495L 78.3%	P495L	P495L 99.0%
			NS5B	None	None	P495L	P495S 20.0%	P495L	P495L 99.0%
9	GT1b	Detectable at EOT	NS3	None	None	A156V	A156V 99.8%	None	None
9	GT1b	Detectable at EOT	NS5B	None	None	P495L	P495L 79.1%	None	None
10	GT1b	Viral relapse	NS3	None	ND	D168T	NA	None	None
10	GT1b	Viral relapse	NS5B	V499A	ND	V499A	NA	V499A	V499A 99.4%
11	GT1b	Viral relapse	NS3	None	None	D168V	D168V 99.8%	None	None
11	GT1b	Viral relapse	NS5B	None	None	P495S	P495S 99.5%	None	None
Panel 3
12	GT1a	Detectable at EOT	NS3	None	ND	Q80R + R155K	ND	Q80R	ND
12	GT1a	Detectable at EOT	NS5B	None	ND	P495L	ND	None	ND
13	GT1b	Viral breakthrough	NS3	None	ND	D168V	ND	D168V	ND
13	GT1b	Viral breakthrough	NS5B	None	ND	P495S	ND	None	ND
14	GT1b	Detectable at EOT	NS3	Q80R	ND	Q80R + D168E	ND	Q80R + D168E	ND
14	GT1b	Detectable at EOT	NS5B	I424V + V499T	ND	I424V + V499T + P495S	ND	I424V + V499T + P495S	ND
15	GT1b	Viral relapse	NS3	None	ND	D168V	ND	D168V	ND
15	GT1b	Viral relapse	NS5B	V37I+ I424V	ND	V37I+ I424V + P495L	ND	V37I+ I424V + P495L	ND
16	GT1b	Viral relapse	NS3	S122T	ND	S122T + D168V	ND	S122T	ND
16	GT1b	Viral relapse	NS5B	None	ND	P495L	ND	None	ND
17	GT1b	Late viral relapse^c	NS3	None	ND	D168A	ND	ND	ND
17	GT1b	Late viral relapse^c	NS5B	V37I	ND	V37I	ND	ND	ND
Panel 4
18	GT1a	Viral breakthrough	NS3	None	None	R155K	Q80R 9.3%	R155K	R155K 79.6%
			NS3	None	None	R155K	R155K 99.5%	R155K	R155K 79.6%
			NS5B	I424V	L392F 3.6%	I424V + P495L	I424L 2.5%	I424V	I424V 81.7%
					I424V 98.3%		I424V 92.2%		V494A 2.1%
					I424V 98.3%		P495L 85.2%		V494A 2.1%
			NS5A	None	M28V 31.3%	Q30E	Q30E 99.2%	Q30E	Q30E 99.3%
19	GT1a	Viral relapse	NS3	None	None	Q80R	Q80R 99.0%	Q80R	Q80R 99.7%
			NS5B	None	None	None	None	None	None
			NS5A	None	None	Q30R	Q30R 99.1%	Q30R	Q30R 99.6%
20	GT1a	Viral relapse	NS3	S122T	S122T 19.6%	S122T + R155K	S122T 99.7%	S122T + R155K	S122T 98.0%
			NS3	S122T		S122T + R155K	R155K 99.1%	S122T + R155K	R155K 95.5%
			NS5B	None	None	None	None	None	None
			NS5A	None	None	Q30H + L31M	Q30E 2.0%	Q30H + L31M	Q30H 98.3%
							Q30H 93.6%		L31M 98.6%
							L31M 94.1%		L31M 98.6%
21^d	GT1a	Viral relapse	NS3	None	None	R155K	R155K 99.4%	R155K	R155K 99.5%
			NS5B	None	None	None	None	None	None
			NS5A	None	None	Q30E	Q30E 99.0%	Q30E	Q30E 99.5%
22	GT1a	Viral relapse	NS3	Q80K	Q80K 97.7%	Q80K + R155S	Q80K 99.8%	Q80K	Q80K 97.0%
			NS3	Q80K	Q80K 97.7%	Q80K + R155S	R155S 99.8%	Q80K	R155S 8.2%
			NS5B	None	None	P495L	P495L 99.6%	P495L	P495L 85.9%
			NS5A	M28V	M28V 23.3%	L31M	L31M 99.7%	L31M	M28A 9.4%
			NS5A	M28V	M28V 23.3%	L31M	L31M 99.7%	L31M	L31M 87.0%

^aAmino acid substitutions are described considering six NS3 positions of interest (43, 80, 122, 155, 156 and 168), 18 NS5B positions of interest (37, 392, 393, 395, 396, 399, 424, 425, 428, 429, 492, 493, 494, 495, 496, 499, 500 and 503) and five NS5A positions of interest (28, 30, 31, 32 and 93). RAVs (i.e. amino acid substitutions, when introduced as SDM in a GT1a or GT1b replicon, associated with a fold change in EC₅₀ > 2.0) are underlined. Absence of amino acid substitutions considering the positions of interest is indicated with ‘none’. DS data are reported when available for all genes of interest at a specific time point. ^bAmino acid substitutions shown in bold indicate emerging amino acid substitutions compared to baseline, based on PS. ^cLate viral relapse defined as subject with SVR12 but with HCV RNA ≥25 IU/mL at follow-up week 24 visit, the last scheduled visit in the study. ^dFor subject 21, end of study DS data were not available, instead data from the follow-up week 12 visit are shown
DS deep sequencing, EC ₅₀ 50% effective concentration, EOT end of treatment, GT genotype, HCV hepatitis C virus, NA not available (no DS data available due to failure of amplification or Illumina DS reaction), ND not determined, PS population sequencing, Pt patient, RAV resistance-associated variant, SDM site-directed mutant, SVR12 sustained virologic response 12 weeks after actual end of treatment

Back to article page

ISSN: 1743-422X

Contact us

Submission enquiries: journalsubmissions@springernature.com