Table 3.
Natural prevalence of NS3/4A inhibitor resistance-associated variants (RAVs) detected by population sequencing and mean fold change in resistance associated with RAVs.
| Position | Variant | Resistant to | Natural prevalence in HCV genotype | Mean fold change in resistance compared to wild-type replicon |
References | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1a | 1b | 2 | 3 | 4 | 5 | 6 | Boceprevir | Telaprevir | Simeprevir | Asunaprevir | Paritaprevir | Vaniprevir | ||||
| V36 | A/C/G | BOC/TVR/PTV | n.o. | n.o. | n.d. | n.d. | n.d. | n.d. | n.d. | [87, 142, 143] | ||||||
| V36 | M | BOC/TVR | 0.2–0.6% | 0.1% | n.d. | n.d. | n.d. | n.d. | n.d. | 3 (GT 1a) | 2 (GT 1a) | 2 (GT 1a) | [87, 142–147] | |||
| F43 | I/L/S/V | SMV/ASV/PTV | n.o. | n.o. | n.d. | n.d. | n.d. | n.d. | n.d. | [86, 87, 148, 149] | ||||||
| T54 | A | BOC/TVR | 0.1–1.9% | n.o. | n.d. | n.d. | n.d. | n.d. | n.d. | 2 (GT 1a) 3 (GT 1b) |
[87, 144, 147, 150–153] | |||||
| T54 | S | BOC/TVR | 0.4–3.1% | 1.2–2.0% | n.d. | n.d. | n.d. | n.d. | n.d. | [87, 142, 143, 149] | ||||||
| V55 | A | BOC/TVR | 2.8% | 0.4% | n.d. | n.d. | n.d. | n.d. | n.d. | 3 (GT 1b) | 1 (GT 1b) | [87, 145–147, 153] | ||||
| Y56 | H | PTV | n.o. | n.o. | n.d. | n.d. | n.d. | n.d. | n.d. | [86, 87, 144] | ||||||
| Q80 | K | SMV/ASV/PTV | 4.8–75.0% | 0.5–1.2% | n.d. | n.d. | n.d. | n.d. | n.d. | 11 (GT 1a) 8 (GT 1b) |
3 (GT 1a) 1 (GT 1b) |
[144, 146, 147, 154] | ||||
| Q80 | R | SMV/ASV | 0.8% | 0.6–0.7% | n.d. | n.d. | n.d. | n.d. | n.d. | 6 | 1 | [86, 87, 89, 144] | ||||
| S122 | R | SMV/ASV | n.o. | n.o. | n.d. | n.d. | n.d. | n.d. | n.d. | 21 | [86, 144, 150] | |||||
| R155 | K/I/G/L/M/T/Q/S | BOC/TVR/SMV/ASV/PTV | 0.2–0.9% | n.o. | n.d. | n.d. | n.d. | n.d. | n.d. | [87, 142] | ||||||
| A156 | F/N/S/T/V | BOC/TVR/SMV/ASV/PTV | n.o. | n.o. | n.d. | n.d. | n.d. | n.d. | n.d. | [86, 87, 89, 142, 148, 149] | ||||||
| V158 | I | BOC | n.o. | 0.1% | n.d. | n.d. | n.d. | n.d. | n.d. | [87, 143] | ||||||
| D168 | E | SMV/ASV/PTV | 0.2–0.3% | 0.1–1.4% | n.d. | n.d. | n.d. | n.d. | n.d. | 38 (GT 1b) | 58 (GT 1a) 78 (GT 1b) |
14 (GT 1a) | [86, 87, 89, 100, 142, 148, 149, 153, 155] | |||
| D168 | G/H/V/TY | SMV/ASV/PTV | n.o. | n.o. | n.d. | n.d. | n.d. | n.d. | n.d. | [86, 87, 148] | ||||||
| V170 | A | BOC/TVR | n.a. | 0.1% | n.d. | n.d. | n.d. | n.d. | n.d. | [87, 142] | ||||||
| M175 | L | BOC | n.a. | 0.8–1.1% | n.d. | n.d. | n.d. | n.d. | n.d. | [87, 143] | ||||||
BOC: boceprevir; TVR: telaprevir; SMV: simeprevir; ASV: asunaprevir; PTV: paritaprevir.
n.a.: not applicable because of different natural amino acid sequence in the respective HCV geno-/subtype (V170 and M175 are the dominant amino acids in GT1b).
n.o.: not observed.
n.d.: no data available.
GT: genotype.