Table 1: Characteristics of HCV direct-acting antiviral classes.

CharacteristicProtease inhibitorsProtease inhibitorsPolymerase inhibitorsPolymerase inhibitorsNS5A inhibitors

First generationSecond generationNucleoside analogs Non-nucleoside analogs

PotencyHigh Variable among HCV genotypesHigh VariableModerate Consistent across genotypesVariable Variable among HCV genotypesHigh Multiple HCV genotypes

Barrier to resistanceLowLowHighVery lowLow

PKVariable qd-tidqdqdVariable qd-tidqd

Adverse eventRash (SJS, TEN), anemia, hyperbilirubinemia appetite loss, renal toxicity, elevation of uric acidAnemia hyperbilirubinemiaMitochondrial nuclear interaction (RBV)VariableVariable

Drug Telaprevir Boceprevir Simeprevir Asunaprevir FaldaprevirSofosbuvir MericitabineBMS-791325Daclatasvir

Clinical trialTVR: 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]

CommentsBetter barrier, pan-genotypicSingle target active siteAllosteric, many targetsMultiple 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.