ACCELERATEinvestigators. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3

Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA.
New England Journal of Medicine (Impact Factor: 55.87). 07/2007; 357(2):124-34. DOI: 10.1056/NEJMoa066403
Source: PubMed


Patients infected with hepatitis C virus (HCV) genotype 2 or 3 have sustained virologic response rates of approximately 80% after receiving treatment with peginterferon and ribavirin for 24 weeks. We conducted a large, randomized, multinational, noninferiority trial to determine whether similar efficacy could be achieved with only 16 weeks of treatment with peginterferon alfa-2a and ribavirin.
We randomly assigned 1469 patients with HCV genotype 2 or 3 to receive 180 mug of peginterferon alfa-2a weekly, plus 800 mg of ribavirin daily, for either 16 or 24 weeks. A sustained virologic response was defined as an undetectable serum HCV RNA level (<50 IU per milliliter) 24 weeks after the end of treatment.
The study failed to demonstrate that the 16-week regimen was noninferior to the 24-week regimen. The sustained virologic response rate was significantly lower in patients treated for 16 weeks than in patients treated for 24 weeks (62% vs. 70%; odds ratio for 16 weeks vs. 24 weeks, 0.67; 95% confidence interval, 0.54 to 0.84; P<0.001). In addition, the rate of relapse (a detectable HCV RNA level during follow-up in patients who had undetectable HCV RNA at the end of treatment) was significantly greater in the 16-week group (31%, vs. 18% in the 24-week group; P<0.001). The sustained virologic response rates in patients with a pretreatment serum HCV RNA level of 400,000 IU per milliliter or less was 82% with the 16-week regimen and 81% with the 24-week regimen. Among patients with a rapid virologic response (an undetectable HCV RNA level by week 4), sustained virologic response rates were 79% in the 16-week group and 85% in the 24-week group (P=0.02).
Treatment with peginterferon and ribavirin for 16 weeks in patients infected with HCV genotype 2 or 3 results in a lower overall sustained virologic response rate than treatment with the standard 24-week regimen. ( number, NCT00077636 [].).

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    • "This combination therapy could increase the sustained virologic response (SVR) rates to ~50% in patients with HCV genotypes 1 and 4, and ~80% in patients with HCV genotypes 2 and 3. Response is genotype dependent8910. This therapy is difficult to tolerate, coupled with many toxicities and serious side effects, which makes patients discontinue their treatment111213. Therefore, there is intense interest in the development of more effective HCV replication inhibitors with less side effects. "
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    • "A number of studies have investigated shortened courses of treatment to minimize adverse effects and costs without compromising efficacy. In patients with chronic HCV genotype 2 or 3 who had undetectable HCV-RNA at 4 weeks of therapy (rapid virologic response), a shorter PEG-IFNα and ribavirin regimen (12–24 weeks) was associated with SVR rates similar to those achieved with 48 weeks of treatment.53,54 Clinical trials have also demonstrated the efficacy of 24 weeks of combination PEG-IFN and ribavirin therapy in patients with chronic hepatitis genotype 1 and 4, who achieved a rapid virologic response defined as undetectable viremia after 4 weeks of treatment.50,51,58–60 "
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