PHE HCV Resistance Group: consensus recommendations

  • Bradshaw D & al.
  • J Infect
  • 16 Oct 2019

  • International Clinical Digest
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Takeaway

  • 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.

Key points

  • 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.