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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 Baselinea Time of failurea End of studya
     PS DS PSb DS PSb DS
Panel 1
1 GT1a Viral breakthrough NS3 None None D168V D168F 48.7% R155K R155K 7.8%
D168V 50.4% 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
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%
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%
P495A 32.5%
6 GT1a Late viral relapsec NS3 None None D168A ND ND ND
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%
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%
P495S 20.0%
9 GT1b Detectable at EOT NS3 None None A156V A156V 99.8% None None
NS5B None None P495L P495L 79.1% None None
10 GT1b Viral relapse NS3 None ND D168T NA None None
NS5B V499A ND V499A NA V499A V499A 99.4%
11 GT1b Viral relapse NS3 None None D168V D168V 99.8% None None
NS5B None None P495S P495S 99.5% None None
Panel 3
12 GT1a Detectable at EOT NS3 None ND Q80R+R155K ND Q80R ND
NS5B None ND P495L ND None ND
13 GT1b Viral breakthrough NS3 None ND D168V ND D168V ND
NS5B None ND P495S ND None ND
14 GT1b Detectable at EOT NS3 Q80R ND Q80R + D168E ND Q80R + D168E ND
NS5B I424V + V499T ND I424V + V499T + P495S ND I424V + V499T + P495S ND
15 GT1b Viral relapse NS3 None ND D168V ND D168V ND
NS5B V37I+ I424V ND V37I+ I424V + P495L ND V37I+ I424V + P495L ND
16 GT1b Viral relapse NS3 S122T ND S122T + D168V ND S122T ND
NS5B None ND P495L ND None ND
17 GT1b Late viral relapsec NS3 None ND D168A ND ND ND
NS5B V37I ND V37I ND ND ND
Panel 4
18 GT1a Viral breakthrough NS3 None None R155K Q80R 9.3% R155K R155K 79.6%
R155K 99.5%
NS5B I424V L392F 3.6% I424V + P495L I424L 2.5% I424V I424V 81.7%
I424V 98.3% I424V 92.2% V494A 2.1%
P495L 85.2%
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%
  R155K 99.1% 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%
21d 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%
R155S 99.8% 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%
L31M 87.0%
  1. 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
  2. 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