Treatment-experienced Genotype 1

Six highly potent oral DAA combination regimens are Recommended for patients with HCV genotype 1 infection, although there are differences in the Recommended regimens based on the viral subtype and the presence or absence of baseline NS5A resistance-associated substitutions (RASs), and the presence or absence of cirrhosis. With certain regimens, patients infected with genotype 1a may have higher rates of virologic failure than those infected with genotype 1b. HCV genotype 1 infection that cannot be subtyped should be treated as genotype 1a infection.

Approximately 10%-15% of HCV genotype 1-infected patients without prior exposure to NS5A inhibitors will have detectable HCV NS5A RASs at the population level prior to treatment. While the clinical impact of NS5A RASs remains to be fully elucidated, in patients with genotype 1a infection the presence of baseline NS5A RASs that cause a large reduction in the activity of NS5A inhibitors (>5 fold) adversely impacts response to NS5A-containing regimens (Zeuzem, 2017); (Jacobson, 2015b). These RASs include substitutions at positions M28, Q30, L31, and Y93 in genotype 1a and are found by population sequencing in roughly 5%-10% of patients. Given that baseline NS5A RASs are one of the strongest pre-treatment predictors of treatment outcome with certain regimens in patients with genotype 1a infection, testing for these RASs prior to deciding on a therapeutic course is recommended in select situations (Zeuzem, 2015c).

The introduction of DAAs into HCV treatment regimens increased the risk of drug interactions with concomitant medications and now with combinations of DAAs, attention to drug interactions is all the more important (see Drug Interactions table). The product prescribing information and other resources (eg, should be referenced regularly to ensure safety when prescribing DAA regimens. Important interactions with commonly used medications (eg, antacids, lipid-lowering drugs, anti-epileptics, antiretrovirals, etc) exist for all of the regimens discussed below.


The following pages include guidance for management of treatment-experienced patients with HCV Genotype 1.


Last update: 
April 12, 2017