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Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. McHutchison JG, Everson GT, Gordon SC, Jacobson IM, Sulkowski M, Kauffman R, McNair L, Alam J, Muir AJ; PROVE1 Study Team. Background: Current therapy for chronic hepatitis C virus (HCV) infection is effective in less than 50% of patients infected with HCV genotype 1. Telaprevir, a protease inhibitor specific to the HCV nonstructural 3/4A serine protease, rapidly reduced HCV RNA levels in early studies. Methods: We randomly assigned patients infected with HCV genotype 1 to one of three telaprevir groups or to the control group. The control group (called the PR48 group) received peginterferon alfa-2a (180microg per week) and ribavirin (1000 or 1200mg per day, according to body weight) for 48weeks, plus telaprevir-matched placebo for the first 12weeks (75 patients). The telaprevir groups received telaprevir (1250mg on day 1 and 750mg every 8hours thereafter) for 12weeks, as well as peginterferon alfa-2a and ribavirin (at the same doses as in the PR48 group) for the same 12weeks (the T12PR12 group, 17 patients) or for a total of 24weeks (the T12PR24 group, 79 patients) or 48weeks (the T12PR48 group, 79 patients). The primary outcome was a sustained virologic response (an undetectable HCV RNA level 24weeks after the end of therapy). Results: The rate of sustained virologic response was 41% (31 of 75 patients) in the PR48 group, as compared with 61% (48 of 79 patients) in the T12PR24 group (P=0.02), 67% (53 of 79 patients) in the T12PR48 group (P=0.002), and 35% (6 of 17 patients) in the T12PR12 group (this group was exploratory and not compared with the control group). Viral breakthrough occurred in 7% of patients receiving telaprevir. The rate of discontinuation because of adverse events was higher in the three telaprevir-based groups (21%, vs. 11% in the PR48 group), with rash the most common reason for discontinuation. Conclusions: Treatment with a telaprevir-based regimen significantly improved sustained virologic response rates in patients with genotype 1 HCV, albeit with higher rates of discontinuation because of adverse events. (ClinicalTrials.gov number, NCT00336479.) [Abstract reproduced by permission of N Engl J Med 2009;360:1827–1838] Telaprevir and peginterferon with or without ribavirin for chronic HCV infection. Hezode C, Forestier N, Dusheiko G, Ferenci P, Pol S, Goeser T, Bronowicki JP, Bourliere M, Gharakhanian S, Bengtsson L, McNair L, George S, Kieffer T, Kwong A, Kauffman RS, Alam J, Pawlotsky JM, Zeuzem S, PROVE2 Study Team. Background: In patients with chronic infection with hepatitis C virus (HCV) genotype 1, treatment with peginterferon alfa and ribavirin for 48weeks results in rates of sustained virologic response of 40 to 50%. Telaprevir is a specific inhibitor of the HCV serine protease and could be of value in HCV treatment. Methods: A total of 334 patients who had chronic infection with HCV genotype 1 and had not been treated previously were randomly assigned to receive one of four treatments involving various combinations of telaprevir (1250mg on day 1, then 750mg every 8hours), peginterferon alfa-2a (180microg weekly), and ribavirin (dose according to body weight). The T12PR24 group (81 patients) received telaprevir, peginterferon alfa-2a, and ribavirin for 12weeks, followed by peginterferon alfa-2a and ribavirin for 12 more weeks. The T12PR12 group (82 patients) received telaprevir, peginterferon alfa-2a, and ribavirin for 12weeks. The T12P12 group (78 patients) received telaprevir and peginterferon alfa-2a without ribavirin for 12weeks. The PR48 (control) group (82 patients) received peginterferon alfa-2a and ribavirin for 48weeks. The primary end point, a sustained virologic response (an undetectable HCV RNA level 24weeks after the end of therapy), was compared between the control group and the combined T12P12 and T12PR12 groups. Results: The rate of sustained virologic response for the T12PR12 and T12P12 groups combined was 48% (77 of 160 patients), as compared with 46% (38 of 82) in the PR48 (control) group (P=0.89). The rate was 60% (49 of 82 patients) in the T12PR12 group (P=0.12 for the comparison with the PR48 group), as compared with 36% (28 of 78 patients) in the T12P12 group (P=0.003; P=0.20 for the comparison with the PR48 group). The rate was significantly higher in the T12PR24 group (69% [56 of 81 patients]) than in the PR48 group (P=0.004). The adverse events with increased frequency in the telaprevir-based groups were pruritus, rash, and anemia. Conclusions: In this phase 2 study of patients infected with HCV genotype 1 who had not been treated previously, one of the three telaprevir groups had a significantly higher rate of sustained virologic response than that with standard therapy. Response rates were lowest with the regimen that did not include ribavirin. (ClinicalTrials.gov number, NCT00372385.) [Abstract reproduced by permission of N Engl J Med 2009;360:1839–1850]

Serum HBeAg levels and HBe-seroconversion were investigated in patients with chronic HBeAg-positive hepatitis who were randomized to receive either alpha lymphoblastoid interferon (5 megaunits subcutaneously daily for 16 weeks) plus acyclovir (2 g intravenously daily during weeks 1 and 2 and weeks 9 and 10) (n = 49) or no treatment (n = 48). HBeAg levels in serial dilutions of patient serum were assessed quantitatively by radioimmunoassay and compared with the values found for negative control serum. One year after the start of therapy 44 treated patients and 43 control patients were available for follow-up. A complete response (HBe-seroconversion) occurred in 11 treated patients (25%) and six controls (14%) (difference: 11%, 95% CI-5-28%). A partial response (HBeAg less than 50% of initial level) was found significantly more often for treated patients (n = 13, 30%) than for controls (n = 2, 5%) (difference: 25%, 95% CI 10-40%). During acyclovir-interferon combination therapy the decrease in HBeAg level was similar to that achieved during therapy with interferon alone. We conclude that acyclovir does not enhance the effect of interferon on serum HBeAg levels. Since HBeAg levels continue to decline during interferon treatment and rebound thereafter to pretreatment levels, prolongation of therapy may yield a higher response rate.