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 G. Mchutchison
(16)
,
Andrew J. 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 A. 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 S. Saag
,
Eugene Schiff
,
Aasim Sheikh
,
Mitchell L. Shiffman
,
Coleman Smith
,
Mark Sulkowski
,
Kimberly Workowski
,
Ziad Younes
1
Beth Israel Medical Centre
2 Johann Wolfgang Goethe University Medical Center
3 Indiana University School of Medicine
4 University of California Medical Center [San Diego]
5 AGA - Atlanta Gastroenterology Associates
6 Department of infectious Diseases
7 Unit for The Clinical Management of Digestive Diseases and CIBERehd
8 Département de Gastroentérologie et hépatologie
9 Institute of Liver Studies
10 Asklepios Klinik St. Georg Hamburg
11 QMUL - Queen Mary University of London
12 James J. Peters VA Medical Center [New York]
13 Vall d'Hebron University Hospital [Barcelona]
14 ISC - Instituto de Salud Carlos III [Madrid]
15 Weill Medical College of Cornell University [New York]
16 Gilead Sciences, Inc. [Foster City, CA, USA]
17 Division of Gastroenterology
18 IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo]
19 Service d'hépatologie
20 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
21 Service d'Hépato-gastro-entérologie [CHRU Nancy]
2 Johann Wolfgang Goethe University Medical Center
3 Indiana University School of Medicine
4 University of California Medical Center [San Diego]
5 AGA - Atlanta Gastroenterology Associates
6 Department of infectious Diseases
7 Unit for The Clinical Management of Digestive Diseases and CIBERehd
8 Département de Gastroentérologie et hépatologie
9 Institute of Liver Studies
10 Asklepios Klinik St. Georg Hamburg
11 QMUL - Queen Mary University of London
12 James J. Peters VA Medical Center [New York]
13 Vall d'Hebron University Hospital [Barcelona]
14 ISC - Instituto de Salud Carlos III [Madrid]
15 Weill Medical College of Cornell University [New York]
16 Gilead Sciences, Inc. [Foster City, CA, USA]
17 Division of Gastroenterology
18 IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo]
19 Service d'hépatologie
20 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
21 Service d'Hépato-gastro-entérologie [CHRU Nancy]
Manuel Romero-Gomez
- Function : Author
- PersonId : 914909
Maria Buti
- Function : Author
- PersonId : 887014
Alessandra Mangia
- Function : Author
- PersonId : 886918
Marc Bourlière
- Function : Author
- PersonId : 900179
Jean-Pierre Bronowicki
- Function : Author
- PersonId : 900180
Christophe Hezode
- Function : Author
- PersonId : 881467
Vlad Ratziu
- Function : Author
- PersonId : 901286
Lawrence Serfaty
- Function : Author
- PersonId : 760409
- ORCID : 0000-0003-3055-5579
Thomas Berg
- Function : Author
Peter Gallert
- Function : Author
- PersonId : 1021192
Guido Gerken
- Function : Author
Tobias Goeser
- Function : Author
Ansgar Lohse
- Function : Author
- PersonId : 783656
- ORCID : 0000-0002-8823-3129
Stefan Mauss
- Function : Author
Robert Thimme
- Function : Author
Hans Wedemeyer
- Function : Author
Alfredo Alberti
- Function : Author
Pietro Andreone
- Function : Author
Mario Angelico
- Function : Author
Massimo Colombo
- Function : Author
- PersonId : 915067
Antonio Craxi
- Function : Author
- PersonId : 912703
Mario Rizzetto
- Function : Author
Maribel Rodriguez-Torres
- Function : Author
Raúl Andrade
- Function : Author
F. Javier Crespo
- Function : Author
Xavier Forns
- Function : Author
- PersonId : 902771
Javier García-Samaniego
- Function : Author
Ashley Brown
- Function : Author
Matthew Cramp
- Function : Author
Geoffrey Dusheiko
- Function : Author
David Mutimer
- Function : Author
Andrew Ustianowski
- Function : Author
Christopher Albers
- Function : Author
Sanjeev Arora
- Function : Author
Kimberly Beavers
- Function : Author
Michael A. Bennett
- Function : Author
- PersonId : 980173
David Bernstein
- Function : Author
Robert Brown Jr.
- Function : Author
Raymond Chung
- Function : Author
James Cooper
- Function : Author
Mitchell Davis
- Function : Author
Adrian Di Bisceglie
- Function : Author
Robin Dretler
- Function : Author
Richard Elion
- Function : Author
Gregory Everson
- Function : Author
Steven Flamm
- Function : Author
Bradley Freilich
- Function : Author
Michael Fried
- Function : Author
Joseph Galati
- Function : Author
Reem Ghalib
- Function : Author
Stuart Gordon
- Function : Author
Steven-Huy Han
- Function : Author
Trevor Hawkins
- Function : Author
Robert Herring
- Function : Author
Federico Hinestrosa
- Function : Author
Lennox Jeffer
- Function : Author
Kris V Kowdley
- Function : Author
Marcelo Kugelmas
- Function : Author
Eric Lawitz
- Function : Author
William Lee
- Function : Author
Timothy R Morgan
- Function : Author
Ronald Nahass
- Function : Author
David Nelson
- Function : Author
Mindie Nguyen
- Function : Author
Keyur Patel
- Function : Author
Paul Pockros
- Function : Author
Gary Poleynard
- Function : Author
John Poterucha
- Function : Author
John Poulos
- Function : Author
David Pound
- Function : Author
Ronald Pruitt
- Function : Author
Natarajan Ravendhran
- Function : Author
K. Rajender Reddy
- Function : Author
Robert Reindollar
- Function : Author
Lorenzo Rossaro
- Function : Author
Peter Ruane
- Function : Author
Vinod Rustgi
- Function : Author
Michael Ryan
- Function : Author
Michael S. Saag
- Function : Author
Eugene Schiff
- Function : Author
Aasim Sheikh
- Function : Author
Mitchell L. Shiffman
- Function : Author
Coleman Smith
- Function : Author
Mark Sulkowski
- Function : Author
Kimberly Workowski
- Function : Author
Ziad Younes
- Function : Author
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.