- Public Health England HCV Resistance Group’s consensus on HCV resistance testing reinforces use in situations where increased virologic failure risk occurs with sustained virologic response at 12-week post-treatment cessation (SVR12)
- Consensus also supports use of second-generation direct-acting antiviral (DAA) therapies that promote treatment scale-up.
Why this matters
- Gain familiarity with pre-DAA resistance-associated substitutions (RAS) testing considerations/scenarios.
- Consider omitting RAS testing prior to DAA initiation if access to testing is limited or where rapid treatment initiation is important.
- Consider RAS effect on DAA therapy response by patient characteristics (e.g., presence of hepatic cirrhosis, prior treatment history), proposed DAA regimen, and associated drug-drug interactions.
- RAS are either drug-specific (reduced susceptibility to 1 agent) or class-specific (reduced susceptibility to ≥2 agents in same class).
- Resistance to NS5A inhibitors may approach 100% in DAA-exposed population; NS3 RAS may emerge during NS3 protease inhibitor resistance but often become undetectable within months after therapy cessation.
- Consider 5 scenarios for pre-DAA testing, rationale, including NS5A RAS in:
- Genotype (GT)1a prior to elbasvir/grazoprevir.
- GT3a with compensated cirrhosis before sofosbuvir/velpatasvir.
- Patients with decompensated cirrhosis before DAA therapy.
- GT 4-6 subtypes.
- All patients with prior NS3 and/or NS5A inhibitor exposure.