Direct-Acting Antivirals for the Treatment of Chronic Hepatitis C: Open Issues and Future Perspectives

Table 1

Characteristics of HCV direct-acting antiviral classes.

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.