Afdhal, NezamZeuzem, StefanKwo, Paul Y.Chojkier, MarioGitlin, NormanPuoti, MassimoRomero-Gómez, ManuelZarski, Jean PierreAgarwal, KoshBuggisch, PeterFoster, Graham R.Bräu, NorbertButi, MariaJacobson, Ira M.Subramanian, G.ManiDing, XiaoMo, HongmeiYang, Jenny C.Pang, Philip S.Symonds, William T.McHutchison, John G.Muir, Andrew J.Mangia, AlessandraMarcellin, PatrickForns, Xavier2017-12-132017-12-132014-05-150028-4793https://hdl.handle.net/2445/118704BACKGROUND: In phase 2 studies, treatment with the all-oral combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor ledipasvir resulted in high rates of sustained virologic response among previously untreated patients with hepatitis C virus (HCV) genotype 1 infection. METHODS: We conducted a phase 3, open-label study involving previously untreated patients with chronic HCV genotype 1 infection. Patients were randomly assigned in a 1:1:1:1 ratio to receive ledipasvir and sofosbuvir in a fixed-dose combination tablet once daily for 12 weeks, ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir-sofosbuvir for 24 weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: Of the 865 patients who underwent randomization and were treated, 16% had cirrhosis, 12% were black, and 67% had HCV genotype 1a infection. The rates of sustained virologic response were 99% (95% confidence interval [CI], 96 to 100) in the group that received 12 weeks of ledipasvir-sofosbuvir; 97% (95% CI, 94 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir plus ribavirin; 98% (95% CI, 95 to 99) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 97 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir plus ribavirin. No patient in either 12-week group discontinued ledipasvir-sofosbuvir owing to an adverse event. The most common adverse events were fatigue, headache, insomnia, and nausea. CONCLUSIONS: Once-daily ledipasvir-sofosbuvir with or without ribavirin for 12 or 24 weeks was highly effective in previously untreated patients with HCV genotype 1 infection. (Funded by Gilead Sciences; ION-1 ClinicalTrials.gov number NCT01701401.).10 p.application/pdfeng(c) Massachusetts Medical Society, 2014Virus de l'hepatitis CMedicaments antivíricsHepatitis C virusAntiviral agentsinfo:eu-repo/semantics/article6619022017-12-13info:eu-repo/semantics/openAccess24725239