Background
Methods
HCV geno/subtype determination
HCV NS3/4A, NS5B and NS5A sequence analysis
Phenotypic characterisation using a transient replicon assay
Ethical approval
Results
Baseline polymorphisms
Emergence of RAVs
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% |