Treatment-Experienced Genotype 1

Multiple highly potent, DAA combination regimens are recommended for patients with genotype 1 infection. There are differences in the recommended regimens based on viral subtype, the presence or absence of baseline NS5A resistance-associated substitutions (RASs), the presence or absence of compensated cirrhosis, and the type of prior failed regimen(s). Genotype 1 infection that cannot be subtyped should be treated as genotype 1a.

Approximately 10% to 15% of genotype 1 patients without prior exposure to NS5A inhibitors have detectable NS5A RASs prior to treatment. The clinical impact of NS5A RASs varies across regimens and baseline patient characteristics. In patients with genotype 1a, the presence of baseline NS5A RASs that cause a large reduction in the activity of NS5A inhibitors (>5 fold) adversely impacts response to some NS5A inhibitor-containing regimens (Zeuzem, 2017); (Jacobson, 2015b). These RASs are found by population sequencing in roughly 5% to 10% of patients; relevant RASs vary by DAA regimen. Given that baseline NS5A RASs are one of the strongest pretreatment predictors of therapeutic outcome with certain regimens in genotype 1a patients, testing for these RASs prior to deciding on a therapeutic course is recommended in selected situations (Zeuzem, 2015c). For further guidance, please see the Resistance Primer section.

Compared to interferon-based therapy, DAAs are associated with a higher rate of drug interactions with concomitant medications. With combinations of DAAs in the various treatment regimens, attention to drug-drug interactions is that much more important (see Drug Interactions table). The product prescribing information and other resources (eg, should be consulted 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 regimens discussed.

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


Last update: 
November 6, 2019