Direct-acting antivirals for HCV

Direct-acting antivirals for HCV

Direct-acting antivirals for HCV

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DAA Classes - HCV's Kryptonite

Direct-acting antivirals (DAAs) target specific non-structural (NS) proteins in the HCV replication cycle, effectively halting viral production. The main classes are distinguished by their target and suffix.

HCV replication cycle and DAA targets in a hepatocyte

ClassTargetSuffixExample
NS3/4A Protease InhibitorProteolytic cleavage-previrGrazoprevir
NS5A InhibitorViral replication/assembly-asvirLedipasvir
NS5B Polymerase InhibitorRNA synthesis-buvirSofosbuvir

⭐ Sofosbuvir is a nucleotide analog NS5B inhibitor, giving it a high barrier to resistance and pangenotypic activity.

The Antiviral Arsenal - Know Your Suffixes

Direct-acting antivirals (DAAs) are the cornerstone of modern HCV therapy, targeting specific non-structural (NS) proteins. Classification by suffix is key to identifying their mechanism.

📌 Mnemonic: -previr (Protease), -asvir (NS5A), -buvir (NS5B).

Drug ClassSuffixExamplesKey Features
NS3/4A Protease Inhibitors-previrGlecaprevir, GrazoprevirInhibit the viral protease, preventing cleavage of the HCV polyprotein into mature forms.
NS5A Inhibitors-asvirLedipasvir, PibrentasvirBlock the NS5A protein, which is critical for viral RNA replication and virion assembly.
NS5B Polymerase Inhibitors-buvirSofosbuvir, DasabuvirInhibit the RNA-dependent RNA polymerase (NS5B), terminating the viral RNA chain.

Clinical Strategy - Regimens & Risks

  • Pangenotypic Regimens: Preferred for simplifying treatment; effective across all genotypes.
    • Glecaprevir/Pibrentasvir
    • Sofosbuvir/Velpatasvir
  • Pre-Treatment Essentials:
    • Screen for HBV (HBsAg, anti-HBc) to assess reactivation risk.
    • Assess for cirrhosis (e.g., FibroScan) to determine treatment duration.
  • Adverse Effects & Warnings:
    • Common: Headache, fatigue, nausea.
    • ⚠️ Black Box Warning: Risk of HBV reactivation in co-infected patients. May lead to fulminant hepatitis.

⭐ Sustained Virologic Response (SVR) at 12 weeks post-therapy is the marker for cure, achieved in >95% of patients with modern DAA regimens.

  • Direct-acting antivirals (DAAs) target specific HCV non-structural proteins (NS3/4A protease, NS5A, NS5B polymerase).
  • Drug names indicate their target: -previr (protease), -asvir (NS5A), and -buvir (polymerase).
  • Combination therapy is standard to prevent resistance and achieve >95% cure rates (SVR).
  • DAAs are pangenotypic, effective against all major HCV genotypes.
  • Key adverse effects are minimal, typically headache and fatigue.
  • ⚠️ Always screen for HBV before initiating DAA therapy due to the risk of HBV reactivation.
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Practice Questions: Direct-acting antivirals for HCV

Test your understanding with these related questions

A 25-year-old sexually active male presents to an internal medicine physician for a routine health check up after having several unprotected sexual encounters. After appropriate testing the physician discusses with the patient that he is HIV+ and must be started on anti-retroviral treatment. Which of the following medications prescribed acts on the gp41 subunit of the HIV envelope glycoprotein?

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Flashcards: Direct-acting antivirals for HCV

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What type of virus is Hepatitis D? (DNA, RNA (sense), etc.)_____

TAP TO REVEAL ANSWER

What type of virus is Hepatitis D? (DNA, RNA (sense), etc.)_____

Negative sense RNA

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