Table 1.
Characteristic | Protease inhibitors | Protease inhibitors | Polymerase inhibitors | Polymerase inhibitors | NS5A inhibitors |
---|---|---|---|---|---|
First generation | Second generation | Nucleoside analogs | Non-nucleoside analogs | ||
| |||||
Potency | High Variable among HCV genotypes | High Variable | Moderate Consistent across genotypes | Variable Variable among HCV genotypes | High Multiple HCV genotypes |
| |||||
Barrier to resistance | Low | Low | High | Very low | Low |
| |||||
PK | Variable qd-tid | qd | qd | Variable qd-tid | qd |
| |||||
Adverse event | Rash (SJS, TEN), anemia, hyperbilirubinemia appetite loss, renal toxicity, elevation of uric acid | Anemia hyperbilirubinemia | Mitochondrial nuclear interaction (RBV) | Variable | Variable |
| |||||
Drug | Telaprevir Boceprevir | Simeprevir Asunaprevir Faldaprevir | Sofosbuvir Mericitabine | BMS-791325 | Daclatasvir |
| |||||
Clinical trial | TVR: ADVANCE [7], ILLUMINATE [8], REALIZE [9] BCV: SPRINT-2 [10], RESPOND-2 [12] |
SMV: PILLAR [14], ASPIRE [15] ASV: AI447-011 [16] FDV: SILEN-C2 [17], SOUND-C2 [18, 19] |
SOF: ATOMIC [20], ELECTRON [21] MRB: JUMP-C [22], INFORM-1 [23], INFORM-SVR [24] |
DCT: AI447-011 [25] | |
| |||||
Comments | Better barrier, pan-genotypic | Single target active site | Allosteric, many targets | Multiple antiviral mechanisms of action |
PK: pharmacokinetics; qd: once a day; tid: three times a day; RBV: ribavirin.
Modified from [1].
SJS: Stevens-Johnson syndrome; TEN: toxic epidermal necrolysis; TVR: telaprevir; BCV: boceprevir; SMV: simeprevir; ASV: asunaprevir; FDV: faldaprevir; SOF: sofosbuvir; MRB: mericitabine; DCV: daclatasvir.