Protease inhibitors | Nucleos(t)ide polymerase inhibitors | Non-nucleoside polymerase inhibitors | NS5A inhibitors | |
Potency | High (varies by HCV genotype) | Moderate-to-high (consistent across HCV genotypes and subtypes) | Varies by HCV genotype | High (against multiple HCV genotypes) |
Barrier to resistance | Low (1a <1b) | High (1a = 1b) | Very low (1a <1b) | Low (1a <1b) |
Potential for drug interactions | High | Low | Variable | Low-to-moderate |
Toxicity | Rash, anemia, ↑ bilirubin | Mitochondrial toxicity, interactions with HIV antiretrovirals (nucleoside reverse transcriptase inhibitors) and ribavirin* | Variable | Variable |
Dosing | daily to three times daily | daily to twice daily | daily to three times daily | daily |
Comments | Later generation protease inhibitors are expected to have higher barriers to resistance and be pan-genotype | Single target for binding at the active site | Many targets for binding at allosteric sites | Multiple antiviral mechanisms of action |
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