Simeprevir and Different Strains of HCV
From Canadian AIDS Treatment Information Exchange
Like many viruses, there is more than one type or strain of HCV. These strains are called genotypes and are broadly distributed as follows:
- genotype 1 -- found throughout the world and common in North America and Western Europe
- genotype 2 -- found in North America, Europe, Japan (subtypes 2a and 2b), northern Italy (subtype 2c) and West Africa
- genotype 3 -- found throughout the world, particularly in the Indian subcontinent
- genotype 4 -- common in Egypt, the Middle East, sub-Saharan Africa and increasingly in Europe
- genotype 5 -- found in Southern Africa, Spain, France, Belgium and Syria
- genotype 6 -- found in South East Asia
The currently licensed new drugs for HCV treatment -- boceprevir and telaprevir -- are designed primarily for the treatment of genotype 1 HCV infection. However, telaprevir likely also has some activity against genotype 2. The standard treatment for many of these other strains of HCV is a combination of peginterferon and ribavirin.
TMC435 (simeprevir) has activity against a broad range of strains of HCV in lab experiments, so researchers recently explored its activity in participants who were infected with genotypes 2 through 6.
Simeprevir, at a dose of 200 mg once daily, was given as monotherapy for the first week of the study in order to assess if it had anti-HCV activity against the different genotypes of HCV. After this period, participants received peginterferon and ribavirin for up to 37 days. Thirty-seven participants were recruited from clinics in Belgium, Germany and Thailand. Eleven percent of participants had cirrhosis (severe liver damage).
Most participants had a significant decline in their HCV viral load when they were taking simeprevir. This decline in HCV viral load was greatest in participants with genotypes 4 and 6 (a decrease of 3 to 4 logs), followed by genotype 2 (a decrease of 2 to 3 logs) and genotype 5 (a decrease of 2 logs).
Genotype 3 did not respond significantly to simeprevir.
In many cases, HCV viral load became undetectable when participants used dual therapy with peginterferon and ribavirin. Switching to dual therapy with peginterferon and ribavirin did not continue to suppress genotype 4 HCV levels.
While most participants reported side effects -- flu-like symptoms -- the researchers stated that simeprevir was well tolerated and most side effects were of mild-to-moderate intensity.
The present study shows that simeprevir can have significant antiviral activity against some strains or genotypes of HCV. It provides a foundation for designing a study to assess the long-term results of therapy for these other genotypes, particularly genotypes 4, 5, 6 and some subtypes of genotype 2.
Other new anti-HCV drugs also need to be assessed for their activity against multiple subtypes of HCV.
Moreno C, Berg T, Tanwandee T, et al. Antiviral activity of TMC435 monotherapy in patients infected with HCV genotypes 2-6: TMC435-C202, a phase IIa, open-label study. Journal of Hepatology. 2012 Jun;56(6):1247-53.
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