Vasily Isakov1, Vladimir Chulanov2,3, Dzhamal Abdurakhmanov3, Eduard Burnevich3,4, Elena Nurmukhametova5, Galina Kozhevnikova6, Natalya Gankina7, Sergey Zhuravel8, Svetlana Romanova9, Robert H Hyland10, Sophia Lu10, Evguenia S Svarovskaia10, John McNally10, Diana M Brainard10, Vladimir Ivashkin3, Vyacheslav Morozov11, Igor Bakulin12, Martin Lagging13, Konstantin Zhdanov14, Ola Weiland15. 1. a 1 Department of Gastroenterology and Hepatology , Institute of Nutrition , Moscow , Russia. 2. b 2 Central Research Institute of Epidemiology , Moscow , Russia. 3. c 3 Hepatology Unit, Sechenov First State Medical University , Moscow , Russia. 4. d 4 City Clinical Hospital #24 of Moscow Healthcare Department , Moscow , Russia. 5. e 5 Clinic Tour LLC , Moscow , Russia. 6. f 6 Central Scientific and Research Institute of Epidemiology , Moscow , Russia. 7. g 7 Krasnoyarsk Regional Center of AIDS Prevention , Krasnoyarsk , Russia. 8. h 8 Sklifosovsky Scientific Research Institution of Emergency Care of Moscow Healthcare Department , Moscow , Russia. 9. i 9 Center for Prevention and Control AIDS and Infectious Diseases , Saint Petersburg , Russia. 10. j 10 Gilead Sciences , Foster City , CA, USA. 11. k 11 Hepatolog LLC , Samara , Russia. 12. l 12 Propedeutics of Internal Diseases, Gastroenterology and Dietology, I.I. Mechnikov North-West State Medical University , Saint Petersburg , Russia. 13. m 13 Department of Infectious Diseases/Virology , Institute of Biomedicine Sahlgrenska Academy University of Gothenburg , Gothenburg , Sweden. 14. n 14 Kirov Medical Military Academy , Saint Petersburg , Russia. 15. o 15 Department of Internaö Medicine Division of Infectious Diseases , Karolinska Institutet, Karolinska University Hospital Huddinge , Stockholm , Sweden.
Abstract
BACKGROUND: In both Russia and Sweden, the dominant hepatitis C virus (HCV) is genotype 1, but around one-third of patients have genotype 3 infection. For such countries, HCV genotype testing is recommended prior to therapy. An effective pangenotypic therapy may potentially eliminate the need for genotyping. In this study, we evaluated the efficacy and safety of sofosbuvir/velpatasvir for 12 weeks in patients from Russia and Sweden. METHODS: In an open-label, single-arm phase-3 study, patients could have HCV genotype 1-6 infection and were treatment-naïve or interferon treatment-experienced. All patients received sofosbuvir/velpatasvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: Of 122 patients screened, 119 were enrolled and treated. Overall, half (50%) were male, 18% had cirrhosis, and 24% had failed prior interferon-based therapy. In total, 66% of patients were infected with HCV genotype 1 (59% 1b and 7% 1a), 6% with genotype 2, and 29% with genotype 3. The overall SVR12 rate was 99% (118/119, 95% confidence interval 95-100%). One treatment-experienced patient infected with HCV genotype 3 experienced virologic relapse after completing treatment. The most common adverse events were headache (16%) and fatigue (7%). Serious adverse events were observed in four patients, but none were related to treatment. No patients discontinued treatment due to adverse events. CONCLUSION: Sofosbuvir/velpatasvir as a pangenotypic treatment for 12 weeks was highly effective in patients from Russia and Sweden infected with HCV genotypes 1, 2, or 3. Sofosbuvir/velpatasvir was safe and well-tolerated. Clinical trial number: ClinicalTrials.gov NCT02722837.
BACKGROUND: In both Russia and Sweden, the dominant hepatitis C virus (HCV) is genotype 1, but around one-third of patients have genotype 3 infection. For such countries, HCV genotype testing is recommended prior to therapy. An effective pangenotypic therapy may potentially eliminate the need for genotyping. In this study, we evaluated the efficacy and safety of sofosbuvir/velpatasvir for 12 weeks in patients from Russia and Sweden. METHODS: In an open-label, single-arm phase-3 study, patients could have HCV genotype 1-6 infection and were treatment-naïve or interferon treatment-experienced. All patients received sofosbuvir/velpatasvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: Of 122 patients screened, 119 were enrolled and treated. Overall, half (50%) were male, 18% had cirrhosis, and 24% had failed prior interferon-based therapy. In total, 66% of patients were infected with HCV genotype 1 (59% 1b and 7% 1a), 6% with genotype 2, and 29% with genotype 3. The overall SVR12 rate was 99% (118/119, 95% confidence interval 95-100%). One treatment-experienced patient infected with HCV genotype 3 experienced virologic relapse after completing treatment. The most common adverse events were headache (16%) and fatigue (7%). Serious adverse events were observed in four patients, but none were related to treatment. No patients discontinued treatment due to adverse events. CONCLUSION:Sofosbuvir/velpatasvir as a pangenotypic treatment for 12 weeks was highly effective in patients from Russia and Sweden infected with HCV genotypes 1, 2, or 3. Sofosbuvir/velpatasvir was safe and well-tolerated. Clinical trial number: ClinicalTrials.gov NCT02722837.
Authors: Konstantin Zhdanov; Vasily Isakov; Eduard Burnevich; Svetlana Kizhlo; Igor Bakulin; Vadim Pokrovsky; Liwen Liang; Peggy Hwang; Rohit Talwani; Barbara A Haber; Michael N Robertson Journal: Hepat Med Date: 2020-04-21
Authors: Daniel Fuster; Kaku So-Armah; Debbie M Cheng; Sharon M Coleman; Natalia Gnatienko; Dmitry Lioznov; Evgeny M Krupitsky; Matthew S Freiberg; Jeffrey H Samet Journal: Curr HIV Res Date: 2021 Impact factor: 1.341