Efficacy of Sofosbuvir and Velpatasvir, With and Without Ribavirin, in Patients With Hepatitis C Virus Genotype 3 Infection and Cirrhosis.

In phase 3 trials and real-world settings, smaller proportions of patients with genotype 3 hepatitis C virus (HCV) infection and cirrhosis have a sustained virologic response 12 weeks after treatment (SVR12) with the combination of sofosbuvir and velpatasvir than in patients without cirrhosis. It is unclear whether adding ribavirin to this treatment regimen increases SVRs in patients with genotype 3 HCV infection and cirrhosis. We performed a phase 2 trial of 204 patients with genotype 3 HCV infection and compensated cirrhosis (mean age 51 ± 7.4 years) at 29 sites in Spain from August 19, 2016 through April 18, 2017. Patients were assigned to groups given sofosbuvir and velpatasvir for 12 weeks (n = 101) or sofosbuvir and velpatasvir plus ribavirin for 12 weeks (n = 103). The primary efficacy end point was SVR12. The overall rates of SVR12 were 91% (92 of 101; 95% CI 84-96) for the sofosbuvir-velpatasvir group and 96% (99 of 103; 95% CI 90-99) for the sofosbuvir-velpatasvir plus ribavirin group. In the sofosbuvir-velpatasvir group, a smaller proportion of patients with baseline resistance-associated substitutions (RASs) in nonstructural protein 5A (NS5A) achieved an SVR12 (84%) than did patients without (96%). In the sofosbuvir-velpatasvir plus ribavirin group, baseline RASs had less effect on the proportion of patients with an SVR12 (96% for patients with baseline RASs; 99% for patients without). The most common adverse events (which occurred in ≥10% of patients) were asthenia (12%) in the sofosbuvir-velpatasvir group and asthenia (27%), headache (24%), and insomnia (12%) in the sofosbuvir-velpatasvir plus ribavirin group. Consistent with findings from previous studies, a high rate of patients (91% and 96%) with genotype 3 HCV infection and compensated cirrhosis achieved an SVR12 with sofosbuvir and velpatasvir, with or without ribavirin. Of patients treated with sofosbuvir and velpatasvir without ribavirin, fewer patients with baseline NS5A RASs achieved an SVR12 compared with patients without baseline NS5A. ClinicalTrials.govNCT02781558.

Esteban R ，Pineda JA ，Calleja JL ，Casado M ，Rodríguez M ，Turnes J ，Morano Amado LE ，Morillas RM ，Forns X ，Pascasio Acevedo JM ，Andrade RJ ，Rivero A ，Carrión JA ，Lens S ，Riveiro-Barciela M ，McNabb B ，Zhang G ，Camus G ，Stamm LM ，Brainard DM ，Subramanian GM ，Buti M ... -  《-》

Sofosbuvir Plus Velpatasvir Combination Therapy for Treatment-Experienced Patients With Genotype 1 or 3 Hepatitis C Virus Infection: A Randomized Trial.

Pianko S ，Flamm SL ，Shiffman ML ，Kumar S ，Strasser SI ，Dore GJ ，McNally J ，Brainard DM ，Han L ，Doehle B ，Mogalian E ，McHutchison JG ，Rabinovitz M ，Towner WJ ，Gane EJ ，Stedman CA ，Reddy KR ，Roberts SK ... -  《-》

Sofosbuvir and Velpatasvir for HCV in Patients with Decompensated Cirrhosis.

Curry MP ，O'Leary JG ，Bzowej N ，Muir AJ ，Korenblat KM ，Fenkel JM ，Reddy KR ，Lawitz E ，Flamm SL ，Schiano T ，Teperman L ，Fontana R ，Schiff E ，Fried M ，Doehle B ，An D ，McNally J ，Osinusi A ，Brainard DM ，McHutchison JG ，Brown RS Jr ，Charlton M ，ASTRAL-4 Investigators ... -  《-》

Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection.

Foster GR ，Afdhal N ，Roberts SK ，Bräu N ，Gane EJ ，Pianko S ，Lawitz E ，Thompson A ，Shiffman ML ，Cooper C ，Towner WJ ，Conway B ，Ruane P ，Bourlière M ，Asselah T ，Berg T ，Zeuzem S ，Rosenberg W ，Agarwal K ，Stedman CA ，Mo H ，Dvory-Sobol H ，Han L ，Wang J ，McNally J ，Osinusi A ，Brainard DM ，McHutchison JG ，Mazzotta F ，Tran TT ，Gordon SC ，Patel K ，Reau N ，Mangia A ，Sulkowski M ，ASTRAL-2 Investigators ，ASTRAL-3 Investigators ... -  《-》

Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in Patients With Genotype 1 Hepatitis C Virus Infection in an Open-Label, Phase 2 Trial.

The best regimen to re-treat patients who do not respond to direct-acting antivirals (DAAs) and the feasibility of further shortening regimens is unclear. We assessed the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in patients with hepatitis C virus genotype 1 infection. We performed an open-label trial at 32 sites in the United States and at 2 sites in New Zealand of 197 patients with genotype 1 hepatitis C virus infection, with or without compensated cirrhosis, who were treatment-naive or were treated previously with a DAA. Between March 2, 2015, and September 1, 2015, patients received sofosbuvir-velpatasvir (400 mg/100 mg in a fixed-dose combination) plus GS-9857 (100 mg) once daily for 6-12 weeks, plus ribavirin for 1 treatment group consisting of treatment-naive patients with cirrhosis. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). Among treatment-naive patients without cirrhosis, 71% (24 of 34; 95% confidence interval [CI], 53-85) achieved SVR12 after 6 weeks of treatment and 100% (36 of 36; 95% CI, 90%-100%) achieved SVR12 after 8 weeks of treatment. Among treatment-naive patients with cirrhosis, 94% (31 of 33; 95% CI, 80-99) achieved SVR12 after 8 weeks of treatment and 81% (25 of 31; 95% CI, 63-93) achieved SVR12 after 8 weeks of treatment with ribavirin. Among DAA-experienced patients treated for 12 weeks, 100% without cirrhosis (31 of 31; 95% CI, 89-100) and 100% with cirrhosis (32 of 32; 95% CI, 89-100) achieved SVR12. The most common adverse events were headache, diarrhea, fatigue, and nausea. One patient (<1%) discontinued treatment because of adverse events. In a phase 2 open-label trial, we found 8 weeks of treatment with sofosbuvir-velpatasvir plus GS-9857 to be safe and effective in treatment-naive patients; 12 weeks was safe and effective in patients previously treated with DAAs. The combination was safe and effective in patients with or without compensated cirrhosis. Clinicaltrials.gov no: NCT02378935.

Lawitz E ，Reau N ，Hinestrosa F ，Rabinovitz M ，Schiff E ，Sheikh A ，Younes Z ，Herring R Jr ，Reddy KR ，Tran T ，Bennett M ，Nahass R ，Yang JC ，Lu S ，Dvory-Sobol H ，Stamm LM ，Brainard DM ，McHutchison JG ，Pearlman B ，Shiffman M ，Hawkins T ，Curry M ，Jacobson I ... -  《-》