Triple Therapy for Genotype 1 Hepatitis C Infection

Triple therapy with peginterferon, ribavirin, and a specifically targeted antiviral agent such as a protease inhibitor will soon be available to improve sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) genotype 1. In this industry-funded, open-label, multicenter, phase II trial, researchers assessed the efficacy of 800 mg of boceprevir (thrice daily), an NS3 protease inhibitor, in combination with peginterferon alfa-2b (1.5 µg/kg) and ribavirin (800 to 1400 mg/day).

In all, 520 treatment-naive patients were randomly assigned to one of five regimens:

• Peginterferon plus ribavirin for 48 weeks (control group)

• Peginterferon plus ribavirin for 4 weeks and then both drugs plus boceprevir for 24 weeks

• Peginterferon plus ribavirin for 4 weeks and then both drugs plus boceprevir for 44 weeks

• Peginterferon, ribavirin, and boceprevir for 28 weeks

• Peginterferon, ribavirin, and boceprevir for 48 weeks

Subsequently, 75 patients were randomized to receive triple therapy in which the ribavirin was administered at either the standard dose (800–1400 mg/day) or a lower dose (400–1000 mg/day).

In an intent-to-treat analysis, rates of the primary endpoint — SVR at 24 weeks — were significantly higher in the boceprevir groups (range, 54% with 28-week triple therapy to 75% with 44-week triple therapy preceded by a 4-week lead-in) than in the control group (38%); comparisons with the control group ranged from P=0.013 to P<0.0001. Among the boceprevir groups, the rate of viral breakthrough (with mutations) was nonsignificantly lower in those who received a two-drug lead-in than in those who did not (4% and 9%; P=0.057). Low-dose ribavirin recipients had a high rate of viral breakthrough with resistance. Compared with the control group, the boceprevir groups had higher rates of anemia (55% vs. 34%) and dysgeusia (27% vs. 9%).