ledipasvir + GS-9451 + peginterferon alfa-2a + ribavirin

A four-drug combination therapy for chronic hepatitis C virus (HCV) infection consisting of **ledipasvir**, **GS-9451** (also known as vedroprevir), **peginterferon alfa-2a**, and **ribavirin**. - **Ledipasvir** is a direct-acting antiviral agent, an HCV NS5A inhibitor, blocking viral RNA replication and assembly[1][3]. - **GS-9451 (vedroprevir)** is an investigational HCV NS3/4A protease inhibitor that interferes with viral polyprotein processing, essential for HCV replication[1][3]. - **Peginterferon alfa-2a** is a pegylated interferon that acts as an immunomodulator and antiviral, increasing the immune response to HCV, with extended half-life for once-weekly dosing[2][4][6]. - **Ribavirin** is a nucleoside analog with broad-spectrum antiviral activity, enhancing sustained virologic response rates when combined with interferons and/or direct-acting antivirals[2][4][6]. This combination leverages different mechanisms—direct viral inhibition of HCV replication, protease activity, and host immune modulation—to maximally suppress HCV and reduce the risk of resistance. Ledipasvir and GS-9451 are developed by Gilead Sciences[1][3]. Peginterferon alfa-2a and ribavirin are marketed by several pharmaceutical companies for chronic HCV[2][6]. Clinical use is experimental: triple or quadruple regimens are studied for improved sustained virologic response rates, especially in difficult-to-treat HCV genotype 1, cirrhotic, or treatment-experienced populations[3].