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Copyright ©2014 Baishideng Publishing Group Co.
World J Gastroenterol. Mar 21, 2014; 20(11): 2902-2912
Published online Mar 21, 2014. doi: 10.3748/wjg.v20.i11.2902
Table 1 In vitro resistance profiles according to hepatitis C virus genotypes[36,40,50-54,64]
EC50< 10 pmol/L< 100 pmol/L< 1 nmol/L< 10 nmol/L< 100 nmol/L< 1 μmol/L> 1 μmol/L
DCV
HCV GT
1bWild (2.6 pmol/L)R30E, H23F/93H31F, M, V/93HΔ30/32L
L28ML31F, V30Q/31F30Q/31M/93H
L31MP32L31V/58S
R30QY93H, N30H/31M
37L or 54H/93H
23F/31F
1aWild (6 pmol/L)M28TL31VQ30E, K31V/93H
Q30H, RY93C, HY93N (> 500 nmol/L)
L31M28T/30H
P32L30H/93H
H58D30R/93C
30R/62D
2-6GT2a (JFH1)GT3aGT2a (L31M)GT2a (Y93H)GT2a (F28S)
GT4a, 5a, 6aGT2a (C92R)GT2b (31M)GT3a (Y93H)
GT3a (A30K)GT4a (L30I/Y93R)
GT3a (L31F)
GT4a (R30G)
GT4a (L30H)
ACH-3102
HCV GT
1bWild (7 pmol/L)Y93HP58S/Y93H
L31V31V/93HP58S/T64A/Y93H
1awild (20 pmol/L)Q30R, E, KY93CY93H, N1
Q30HM28T28T/30H/93C1
L31M, VP32L
H58D
2-6GT2a (JFH1)
GT2a (L31M)
GT2b (31M)
GT3a, 4a, 5a, 6a
Table 2 Resistance profiles of hepatitis C virus NS5A inhibitors in hepatitis C virus genotype 1- and 2-infected patients[61,66,73-75]
HCV NS5A inhibitorMean maximal viral decline (log IU/mL)Maximal viral decline in patients with RAVs at baseline (log IU/mL)
HCV genotype 1a-infected
DCV3.8 (60 mg, 14 d)Q30R (10%)2.9
LDV3.1-3.3 (10-90 mg, 3 d)Q30E/Q0.88
L31M0.16
Y93C (12%)1.6
PPI-6683.3 (80-160 mg, 3 d)M28V (50%)3.7
M28T (7%)2.8
M28T (10%)/L31M (11%)3.6
H58D (69%)/N (31%)2.2
IDX7193.2-3.6 (25-100 mg, 3 d)M28M/V3.6
ACH-31023.5-3.9 (50-300 mg, single dose)M28V, T (2%-24%)3.4 to 4
L31M (28%)3.4
Y93C, D, H (2%-3%)4 to 4.6
HCV genotype 1b-infected
DCV4.3 (10 mg, 14 d)Q54H, N> 4
Q54H/Y93H> 4
LDV3.3 (10 mg, 3 d)L31M2.09
PPI-6682.9 (40 mg, 3 d; only 1 patient)R30Q2.9
3.8-4 (80-240 mg, 3 d)L31M4
P58S3.8
L28M (7%), R30Q (76%), L31M (20%)3.5
R30Q/L31I/Y93H0.33
IDX-7193-4.3 (25-50 mg, 3 d)R30Q/Y93H2.8
HCV genotype 2a-infected
PPI-6680.33 (160 mg, 3 d; only 1 patient)F28L/A30K/L31M0.33
IDX-7192.0 (50-100 mg, 3 d)L31M0.45
L31L/M0.85
HCV genotype 2b-infected
PPI-6683.0 (160 mg, 3 d)A30K0.48
Y93H (7%)0.45
Y93H0.25