HCV DAA and ART Interaction — SCE Infectious Diseases MCQ

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HardHepatitisHCV DAA and ART InteractionSCE Infectious Diseases

A 55-year-old man with HIV on ART (CD4 380, VL <50) is co-infected with hepatitis C (genotype 1a, F3 fibrosis, treatment-naive). His ART includes Darunavir/Ritonavir plus Tenofovir AF/Emtricitabine. He is prescribed Glecaprevir/Pibrentasvir for HCV. What is the drug interaction concern?

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Correct answer: A — Ritonavir-boosted Darunavir significantly increases Glecaprevir levels (via CYP3A4/P-gp inhibition) — this combination is contraindicated

Glecaprevir is a substrate of CYP3A4 and P-glycoprotein. Ritonavir (a potent CYP3A4 and P-gp inhibitor used as a pharmacokinetic booster for Darunavir) significantly increases Glecaprevir AUC (>4-fold), increasing the risk of hepatotoxicity. This combination is contraindicated. Alternative approaches: (1) use Sofosbuvir/Velpatasvir instead (minimal interaction with DRV/r), or (2) switch the ART (e.g. to an unboosted INSTI regimen) before starting Glecaprevir/Pibrentasvir. The Liverpool Drug Interactions database should always be consulted.

Reference: BHIVA 2024 – HCV/HIV co-infection; Liverpool Drug Interactions 2024; EASL 2024