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.
| Class | Target | Suffix | Example |
|---|---|---|---|
| NS3/4A Protease Inhibitor | Proteolytic cleavage | -previr | Grazoprevir |
| NS5A Inhibitor | Viral replication/assembly | -asvir | Ledipasvir |
| NS5B Polymerase Inhibitor | RNA synthesis | -buvir | Sofosbuvir |
⭐ 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 Class | Suffix | Examples | Key Features |
|---|---|---|---|
| NS3/4A Protease Inhibitors | -previr | Glecaprevir, Grazoprevir | Inhibit the viral protease, preventing cleavage of the HCV polyprotein into mature forms. |
| NS5A Inhibitors | -asvir | Ledipasvir, Pibrentasvir | Block the NS5A protein, which is critical for viral RNA replication and virion assembly. |
| NS5B Polymerase Inhibitors | -buvir | Sofosbuvir, Dasabuvir | Inhibit 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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