Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection

Nezam Afdhal 1 Stefan Zeuzem 2 Paul Kwo 3 Mario Chojkier 4 Norman Gitlin 5 Massimo Puoti 6 Manuel Romero-Gomez 7 Jean-Pierre Zarski 8 Kosh Agarwal 9 Peter Buggisch 10 Graham Foster 11 Norbert Bräu 12 Maria Buti 13, 14 Ira Jacobson 15 G. Mani Subramanian 16 Xiao Ding 16 Hongmei Mo 16 Jenny Yang 16 Phillip Pang 16 William Symonds 16 John Mchutchison 16 Andrew Muir 17 Alessandra Mangia 18 Patrick Marcellin 19 Marc Bourlière Jean-Pierre Bronowicki 20, 21 Christophe Hezode Vlad Ratziu Lawrence Serfaty Thomas Berg Peter Gallert Guido Gerken Tobias Goeser Ansgar Lohse Stefan Mauss Robert Thimme Hans Wedemeyer Alfredo Alberti Pietro Andreone Mario Angelico Massimo Colombo Antonio Craxi Mario Rizzetto Maribel Rodriguez-Torres Raúl Andrade F. Javier Crespo Xavier Forns Javier García-Samaniego Ashley Brown Matthew Cramp Geoffrey Dusheiko David Mutimer Andrew Ustianowski Christopher Albers Sanjeev Arora Kimberly Beavers Michael Bennett David Bernstein Robert Brown Jr. Raymond Chung James Cooper Mitchell Davis Adrian Di Bisceglie Robin Dretler Richard Elion Gregory Everson Steven Flamm Bradley Freilich Michael Fried Joseph Galati Reem Ghalib Stuart Gordon Steven-Huy Han Trevor Hawkins Robert Herring Federico Hinestrosa Lennox Jeffer Kris V Kowdley Marcelo Kugelmas Eric Lawitz William Lee Timothy R Morgan Ronald Nahass David Nelson Mindie Nguyen Keyur Patel Paul Pockros Gary Poleynard John Poterucha John Poulos David Pound Ronald Pruitt Natarajan Ravendhran K. Rajender Reddy Robert Reindollar Lorenzo Rossaro Peter Ruane Vinod Rustgi Michael Ryan Michael Saag Eugene Schiff Aasim Sheikh Mitchell Shiffman Coleman Smith Mark Sulkowski Kimberly Workowski Ziad Younes
Abstract : Background 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.
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Nezam Afdhal, Stefan Zeuzem, Paul Kwo, Mario Chojkier, Norman Gitlin, et al.. Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection. New England Journal of Medicine, Massachusetts Medical Society, 2014, 370 (20), pp.1889 - 1898. ⟨10.1056/NEJMoa1402454⟩. ⟨hal-01690189⟩

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