Hepatitis C Virus Infection: Looking for Interferon Free Regimens

Table 2

FDA approved directly acting antiviral drugs—telaprevir (Incivek) and boceprevir (Victrelis). Modified from Assis and Lin [9].

	Telaprevir	Boceprevir
Formulation	375 mg oral capsule	200 mg oral capsule
Dosing	750 mg/7–9 h with a fatty meal*	800 mg every 7–9 h with food*
Regimen	12 weeks of triple therapy followed by Peg-IFN/ribavirin alone for 12 or 36 weeks**	Start after 4-week lead-in of Peg-IFN and ribavirin for 24 or 44 weeks**
Discontinuation	If VL >1,000 IU/mL at week 4 or 12, and VL at week 24	If VL >100 IU/mL at week 8, 12, and VL at week 24
Expected SVR	Naive: 69–75%; Relapser: 84–88%; Partial responder: 56–61%; Null responder: 31–33%	Naive: 63–66%; Relapser: 69–75%; Partial responder: 40–52%; Null responder: not studied
RGT	If negative VL at weeks 4 and 12, treat with Peg-IFN/ribavirin for 12 more weeks If not, treat for 36 more weeks**	Treatment-naive: if negative VL at week 8 and 24, complete treatment at week 28; Previously treated: if negative VL at week 8 and 24, complete treatment at week 36**
Barrier to resistance	Low (V3M6, R155K)	Low (V3M6, R155K)
Common adverse effects	Anemia (37%); Rash (56%; severe in 4–7%); Anal itching/burning (29%)	Anemia (49%); Dysgeusia (43%)
Metabolism	Hepatic (CYP450)***	Hepatic (CYP450 and aldoketoreductase)***
Interactions	Strong inhibitor of CYP3A	Strong inhibitor of CYP3A4/5 and is partly metabolized by CYP3A4/5
Renal/hepatic adjustment	Renal: none; Hepatic: do not use if Child-Pugh score >7	Renal: none; Hepatic: do not use if Child-Pugh score >7
FDA-labeled indications	Chronic HCV genotype 1a or 1b in combination with Peg-IFN and ribavirin, in adults with compensated liver disease (Child-Pugh <7)	Chronic HCV genotype 1a or 1b, in combination with Peg-IFN and ribavirin, in adults with compensated liver disease, including cirrhosis, who are previously untreated or who failed previous Peg-IFN/ribavirin treatment
Contraindications	Pregnancy (due to ribavirin); Coadministration with drugs highly dependent on CYP3A for clearance	Pregnancy (due to ribavirin); Coadministration with drugs highly dependent on CYP3A4/5 for clearance
Special populations	Not approved in decompensated cirrhosis, HIV-HCV or HBV-HCV coinfection, pediatrics, and posttransplant	Not approved in decompensated cirrhosis, HIV-HCV or HBV-HCV coinfection, pediatrics, and posttransplant

FDA: US Food and Drug Administration; HBV: hepatitis B virus; HCV: hepatitis C virus; IFN: interferon; R155K: lysine to arginine substitution at position 155; RGT: response guided treatment; SVR: sustained virologic response; VL: viral load; V36M: valine to methionine substitution at position 36. *No dose reduction is allowed because of risk of engender drug resistance. ^∗∗48 weeks of treatment always for patients with cirrhosis and previous null responders. In telaprevir treatment also for partial responders. In boceprevir also for previously untreated patients who respond poorly to interferon in the lead-in period (<1 log 10 decline in hepatitis C RNA from baseline). ***Special care using first-generation protease inhibitors which are hormonal contraceptives, statins, dihydropyridine calcium channel blockers, and phosphodiesterase-5 inhibitors.