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Resistance to Direct Acting Antiviral Therapy

Resistance to Direct Acting Antiviral Therapy. Resistance to HCV DAAs: What is the threat level?. HCV Biology is the basis for resistance. HCV biology is the basis for cure. Frequency of Protease Resistance Mutations Prior to Therapy.

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Resistance to Direct Acting Antiviral Therapy

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  1. Resistance to Direct Acting Antiviral Therapy

  2. Resistance to HCV DAAs: What is the threat level?

  3. HCV Biology is the basis for resistance

  4. HCV biology is the basis for cure

  5. Frequency of Protease Resistance Mutations Prior to Therapy

  6. Emergence of Pre-existing Resistant Variants During Treatment with DAA

  7. Resistance Develops Rapidly During telaprevir monotherapy with Protease Inhibitor

  8. Barrier to resistance: Combination of DAAs with different mechanism of action

  9. Multiple drugs target WT and resistant virus to prevent selection of resistant variants

  10. Inhibitors of NS3/4A Protease

  11. SVR with PegIFN/RBV + PI requires adequate IFN response to prevent resistance

  12. REALIZE: Resistance rates are higher in persons less responsive to PegIFN/RBV

  13. Frequency of RAVs detected in Non-SVR Patients; Poor Interferon Responders and Interferon Responders

  14. Barrier to resistance: Role of viral characteristics Telaprevir Resistance in patients who failed to achieve SVR: Subtype 1a versus 1b

  15. Barrier to resistance: Role of pharmacology Clonal sequence analysis from subjects dosed with ABT-450 for 3 days

  16. Barrier to resistance: Combination therapy

  17. Inhibitors of NS5A Replicase Protein

  18. Daclatasvir: Emergence of resistance with 14 day monotherapy

  19. Potent antiviral activity of GS-58853-day monotherapy

  20. Daclatasvir + Asunaprevir ± PegIFN/RBV in Previous PegIFN/RBV Null Responders

  21. Inhibitors of NS5B polymersase: non-nucleoside inhibitors (NNIs)

  22. Polymerase mutations in 89 treatment naïve HCV genotype 1 infected patients

  23. PI (GS-9256) + NNI (Tegobuvir) with or without RBV for HCV genotype 1

  24. Inhibitors of NS5B polymersase: nucleoside inhibitors (NIs)

  25. Resistance to nucleos(t)ide inhibitors

  26. Antiviral Activity of PSI-7977 alone or in combination with PSI-938

  27. ELECTRON: SVR following GS-7977 ± RBV ± PegIFN x 12 weeks

  28. INFORM-1: Combination of NI + PI may prevent emergence of PI resistant variants

  29. Cyclophilin Antagonists: Target the host

  30. Clinical implications of pre-existing mutations to DAAs – spontaneous or selected

  31. SVR Rates By Treatment Week 4 Response Among Patients With or Without Baseline RAVs Detected

  32. Most Common RAVs†:Detectability Declines During Follow-Up

  33. ADVANCELoss of Resistance by NS3 Position

  34. EXTEND Study: Long-term Follow-up of Patients Treated with Telaprevir

  35. EXTEND study: Follow-up of TLV treated patients

  36. C-219: Retreatment of 9 patients after TVR monotherapy with resistance

  37. Clinical implications of selection resistance to first generation HCV PIs

  38. Resistance to Direct Acting Antiviral Therapy

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