Sofosbuvir and ribavirin in HCV genotypes 2 and 3
Stefan Zeuzem, Geoffrey M Dusheiko, Riina Salupere, Alessandra Mangia, Robert Flisiak, Robert H Hyland, Ari Illeperuma, Evguenia Svarovskaia, Diana M Brainard, William T Symonds, G Mani Subramanian, John G McHutchison, Ola Weiland, Hendrik W Reesink, Peter Ferenci, Christophe Hézode, Rafael Esteban, VALENCE Investigators, Peter Ferenci, Michael Gschwantler, Rudolf E Stauber, Riina Salupere, Kai Zilmer, Armando Abergel, Marc Bourlière, Jean-Pierre Bronowicki, Victor De Lédinghen, Dominique Guyader, François Habersetzer, Christophe Hézode, Dominque Larrey, Patrick Marcellin, Phillipe Mathurin, Stanislas Pol, Vlad Ratziu, Lawrence Serfaty, Albert Tran, Jean-Pierre Zarski, Thomas Berg, Stefan Christensen, Christoph Eisenbach, Norbert Grüner, Dieter Häussinger, Renate Heyne, Holger Hinrichsen, Dietrich Hüppe, Michael P Manns, Jörg Petersen, Martin Roessle, Julian Schulze-zur-Wisch, Ulrich Spengler, Stefan Zeuzem, Alfredo Alberti, Pietro Andreone, Mario Angelico, Giovanni Cassola, Massimo Colombo, Antonio Craxì, Alessandra Mangia, Francesco Mazzota, Alessandra Orlandini, Massimo Puoti, Mario Rizzetto, Ubaldo Visco Comandini, Joost Drenth, Robert de Knegt, Henk Reesink, Bart van Hoek, Robert Flisiak, Andrzej Horban, Maciej Jablkowski, Simon Krzysztof, Raul Andrade, Moises Diago, José Luis Calleja Panero, Rafael Esteban, Xavier Forns, Javier Crespo García, Javier García-Samaniego, Antonio Olveira, Manuel Romero-Gómez, Leo Flamholc, Hans Norrgren, Ola Weiland, Rune Wejstål, Kosh Agarwal, Ashley Brown, Geoff Dusheiko, Andrew Ustianowski, Graham Foster, Mark Wright, Fiona Gordon, Mark Nelson, David Mutimer, Stephen Ryder, Stefan Zeuzem, Geoffrey M Dusheiko, Riina Salupere, Alessandra Mangia, Robert Flisiak, Robert H Hyland, Ari Illeperuma, Evguenia Svarovskaia, Diana M Brainard, William T Symonds, G Mani Subramanian, John G McHutchison, Ola Weiland, Hendrik W Reesink, Peter Ferenci, Christophe Hézode, Rafael Esteban, VALENCE Investigators, Peter Ferenci, Michael Gschwantler, Rudolf E Stauber, Riina Salupere, Kai Zilmer, Armando Abergel, Marc Bourlière, Jean-Pierre Bronowicki, Victor De Lédinghen, Dominique Guyader, François Habersetzer, Christophe Hézode, Dominque Larrey, Patrick Marcellin, Phillipe Mathurin, Stanislas Pol, Vlad Ratziu, Lawrence Serfaty, Albert Tran, Jean-Pierre Zarski, Thomas Berg, Stefan Christensen, Christoph Eisenbach, Norbert Grüner, Dieter Häussinger, Renate Heyne, Holger Hinrichsen, Dietrich Hüppe, Michael P Manns, Jörg Petersen, Martin Roessle, Julian Schulze-zur-Wisch, Ulrich Spengler, Stefan Zeuzem, Alfredo Alberti, Pietro Andreone, Mario Angelico, Giovanni Cassola, Massimo Colombo, Antonio Craxì, Alessandra Mangia, Francesco Mazzota, Alessandra Orlandini, Massimo Puoti, Mario Rizzetto, Ubaldo Visco Comandini, Joost Drenth, Robert de Knegt, Henk Reesink, Bart van Hoek, Robert Flisiak, Andrzej Horban, Maciej Jablkowski, Simon Krzysztof, Raul Andrade, Moises Diago, José Luis Calleja Panero, Rafael Esteban, Xavier Forns, Javier Crespo García, Javier García-Samaniego, Antonio Olveira, Manuel Romero-Gómez, Leo Flamholc, Hans Norrgren, Ola Weiland, Rune Wejstål, Kosh Agarwal, Ashley Brown, Geoff Dusheiko, Andrew Ustianowski, Graham Foster, Mark Wright, Fiona Gordon, Mark Nelson, David Mutimer, Stephen Ryder
Abstract
Background: In clinical trials, treatment with a combination of the nucleotide polymerase inhibitor sofosbuvir and the antiviral drug ribavirin was associated with high response rates among patients with hepatitis C virus (HCV) genotype 2 infection, with lower response rates among patients with HCV genotype 3 infection.
Methods: We conducted a study involving patients with HCV genotype 2 or 3 infection, some of whom had undergone previous treatment with an interferon-based regimen. We randomly assigned 91 patients with HCV genotype 2 infection and 328 with HCV genotype 3 infection, in a 4:1 ratio, to receive sofosbuvir-ribavirin or placebo for 12 weeks. On the basis of emerging data from phase 3 trials indicating that patients with HCV genotype 3 infection had higher response rates when they were treated for 16 weeks, as compared with 12 weeks, the study was unblinded, treatment for all patients with genotype 3 infection was extended to 24 weeks, the placebo group was terminated, and the goals of the study were redefined to be descriptive and not include hypothesis testing. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.
Results: Of the 419 patients who were enrolled and treated, 21% had cirrhosis and 58% had received previous interferon-based treatment. The criterion for a sustained virologic response was met in 68 of 73 patients (93%; 95% confidence interval [CI], 85 to 98) with HCV genotype 2 infection who were treated for 12 weeks and in 213 of 250 patients (85%; 95% CI, 80 to 89) with HCV genotype 3 infection who were treated for 24 weeks. Among patients with HCV genotype 3 infection, response rates were 91% and 68% among those without and those with cirrhosis, respectively. The most common adverse events were headache, fatigue, and pruritus.
Conclusions: Therapy with sofosbuvir-ribavirin for 12 weeks in patients with HCV genotype 2 infection and for 24 weeks in patients with HCV genotype 3 infection resulted in high rates of sustained virologic response. (Funded by Gilead Sciences; VALENCE ClinicalTrials.gov number, NCT01682720.).
Source: PubMed