BACKGROUND & AIMS: We evaluated an all-oral regimen comprising the nucleotide polymerase inhibitor sofosbuvir (SOF) with the NS5A inhibitor ledipasvir (LDV) or the NS5B non-nucleoside inhibitor GS-9669 in patients with genotype 1 hepatitis C virus (HCV) infection. METHODS: A total of 113 patients were enrolled. Sofosbuvir (400 mg once daily) and LDV (90 mg once daily) plus ribavirin (RBV) were given for 12 weeks to treatment-naïve (TN) patients (n = 25) and those who did not respond to previous therapy (prior null responders, n = 9). Sofosbuvir and GS-9669 (500 mg once daily) plus RBV were given for 12 weeks to TN patients (n = 25) and prior null responders (n = 10). Additionally, prior null responders with cirrhosis were randomly assigned to groups given a fixed-dose combination of SOF and LDV, with RBV (n = 9) or without RBV (n = 10). Finally, a group of TN patients received SOF, LDV, and RBV for 6 weeks (n = 25). The primary efficacy end point was sustained virologic response 12 weeks after therapy (SVR12). RESULTS: SVR12 was achieved by 25 of 25 (100%) TN patients receiving SOF, LDV, and RBV and 23 of 25 (92%) of those receiving SOF, GS-9669, and RBV. Of TN patients receiving 6 weeks of SOF, LDV, and RBV, 17 of 25 (68%) achieved SVR12. All noncirrhotic prior null responders receiving 12 weeks of SOF along with another direct-acting antiviral agent plus RBV achieved SVR12-9 of 9 (100%) of those receiving SOF, LDV, and RBV and 10 of 10 (100%) of those receiving SOF, GS-9669, and RBV. Among cirrhotic prior null responders, SVR12 was achieved by 9 (100%) of those receiving SOF, LDV, and RBV and 7 (70%) of those receiving SOF and LDVD without RBV. The most common reported adverse events were headache, fatigue, and nausea. CONCLUSIONS: The combination of SOF and a second direct-acting antiviral agent is highly effective in TN patients with HCV genotype 1 infection and in patients that did not respond to previous treatment. ClinicalTrials.gov ID NCT01260350.
BACKGROUND & AIMS: We evaluated an all-oral regimen comprising the nucleotide polymerase inhibitor sofosbuvir (SOF) with the NS5A inhibitor ledipasvir (LDV) or the NS5B non-nucleoside inhibitor GS-9669 in patients with genotype 1 hepatitis C virus (HCV) infection. METHODS: A total of 113 patients were enrolled. Sofosbuvir (400 mg once daily) and LDV (90 mg once daily) plus ribavirin (RBV) were given for 12 weeks to treatment-naïve (TN) patients (n = 25) and those who did not respond to previous therapy (prior null responders, n = 9). Sofosbuvir and GS-9669 (500 mg once daily) plus RBV were given for 12 weeks to TN patients (n = 25) and prior null responders (n = 10). Additionally, prior null responders with cirrhosis were randomly assigned to groups given a fixed-dose combination of SOF and LDV, with RBV (n = 9) or without RBV (n = 10). Finally, a group of TN patients received SOF, LDV, and RBV for 6 weeks (n = 25). The primary efficacy end point was sustained virologic response 12 weeks after therapy (SVR12). RESULTS: SVR12 was achieved by 25 of 25 (100%) TN patients receiving SOF, LDV, and RBV and 23 of 25 (92%) of those receiving SOF, GS-9669, and RBV. Of TN patients receiving 6 weeks of SOF, LDV, and RBV, 17 of 25 (68%) achieved SVR12. All noncirrhotic prior null responders receiving 12 weeks of SOF along with another direct-acting antiviral agent plus RBV achieved SVR12-9 of 9 (100%) of those receiving SOF, LDV, and RBV and 10 of 10 (100%) of those receiving SOF, GS-9669, and RBV. Among cirrhotic prior null responders, SVR12 was achieved by 9 (100%) of those receiving SOF, LDV, and RBV and 7 (70%) of those receiving SOF and LDVD without RBV. The most common reported adverse events were headache, fatigue, and nausea. CONCLUSIONS: The combination of SOF and a second direct-acting antiviral agent is highly effective in TN patients with HCV genotype 1 infection and in patients that did not respond to previous treatment. ClinicalTrials.gov ID NCT01260350.