simeprevir + ledipasvir + sofosbuvir

A combination of three **direct-acting antiviral agents**—simeprevir (an HCV NS3/4A protease inhibitor), ledipasvir (an HCV NS5A inhibitor), and sofosbuvir (an HCV NS5B polymerase inhibitor)—investigated as an off-label regimen for the treatment of chronic hepatitis C virus (HCV) infection, specifically genotype 1. All three agents are orally administered small molecules that target different essential steps in the HCV replication cycle. This triple combination was studied for pharmacokinetic interactions and antiviral efficacy in HCV-infected patients without cirrhosis. Despite robust antiviral effectiveness (all patients in the referenced Phase 2 trial achieved a sustained virologic response at 12 weeks), the regimen led to significant drug-drug interactions, resulting in increased exposures of both simeprevir and ledipasvir. Safety concerns (mainly increased photosensitivity) and lack of extensive safety data have resulted in the recommendation against routine use of this combination.