Efficacy of 8 Weeks of Sofosbuvir, Velpatasvir, and Voxilaprevir in Patients With Chronic HCV Infection: 2 Phase 3 Randomized Trials

doi:10.1053/J.GASTRO.2017.03.047

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Efficacy of 8 Weeks of Sofosbuvir, Velpatasvir, and Voxilaprevir in Patients With Chronic HCV Infection: 2 Phase 3 Randomized Trials

Journal Article•DOI•

Efficacy of 8 Weeks of Sofosbuvir, Velpatasvir, and Voxilaprevir in Patients With Chronic HCV Infection: 2 Phase 3 Randomized Trials

Ira M. Jacobson¹, Ira M. Jacobson², Eric Lawitz³, Edward Gane⁴, Bernard Willems⁵, Peter Ruane, Ronald Nahass, Sergio Borgia⁶, Stephen D. Shafran⁷, Kimberly A. Workowski⁸, Brian L. Pearlman⁹, Robert H. Hyland, Luisa M. Stamm, Evguenia S. Svarovskaia, Hadas Dvory-Sobol, Yanni Zhu, G. Mani Subramanian, Diana M. Brainard, John G. McHutchison, Norbert Bräu¹⁰, Norbert Bräu¹, Thomas Berg¹¹, Kosh Agarwal¹², Bal Raj Bhandari, M. Davis¹³, Jordan J. Feld¹⁴, Gregory J. Dore¹⁵, Catherine A.M. Stedman¹⁶, Alexander J. Thompson¹⁷, Tarik Asselah¹⁸, Stuart K. Roberts¹⁹, Graham R. Foster²⁰ - Show less +28 more•Institutions (20)

Icahn School of Medicine at Mount Sinai¹, Beth Israel Medical Center², University of Texas Health Science Center at San Antonio³, Auckland City Hospital⁴, Université de Montréal⁵, Brampton Civic Hospital⁶, University of Alberta⁷, Emory University⁸, Atlanta Medical Center⁹, Veterans Health Administration¹⁰, Charité¹¹, King's College¹², Wellington Management Company¹³, Toronto Western Hospital¹⁴, University of New South Wales¹⁵, University of Otago¹⁶, St. Vincent's Health System¹⁷, Paris Diderot University¹⁸, Alfred Hospital¹⁹, Royal London Hospital²⁰

01 Jul 2017-Gastroenterology (Elsevier)-Vol. 153, Iss: 1, pp 113-122

TL;DR: In phase 3 trials of patients with HCV infection, it was not established that sofosbuvir-velpatasvir-voxilaprevir for 8 weeks was noninferior to sofOSbuvir -velpat asvir for 12 weeks, but the 2 regimens had similar rates of SVR in patients withHCV genotype 3 and cirrhosis.

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About: This article is published in Gastroenterology.The article was published on 2017-07-01 and is currently open access. It has received 193 citations till now. The article focuses on the topics: Glecaprevir & Voxilaprevir.

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Journal Article•DOI•

EASL Recommendations on Treatment of Hepatitis C

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Jean-Michel Pawlotsky, Alessio Aghemo, Geoffrey Dusheiko, Xavier Forns, Massimo Puoti, Christophe Sarrazin - Show less +2 more

01 Aug 2018-Journal of Hepatology

TL;DR: The optimal management of patients with acute and chronic HCV infections in 2018 and onwards is described, as well as developments in diagnostic procedures and improvements in therapy and prevention.

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2,491 citations

Cites background or methods from "Efficacy of 8 Weeks of Sofosbuvir, ..."

...The addition of voxilaprevir was associated with more frequent benign diarrhoea (18% and 15% in patients receiving the triple combination and 7% and 5% in those receiving sofosbuvir and velpatasvir only in the POLARIS-2 and POLARIS-3 trials, respectively).(71)...
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...In POLARIS-3, 8 weeks of the triple combination yielded a 96% SVR12 rate (106/110; 2 relapses) in treatment-naïve and treatment-experienced patients with compensated cirrhosis.(71) Because genotype 3 is more difficult-to-cure than other genotypes, and in the absence of data with 12 weeks of therapy, it appears to be safer to treat patients with genotype 3 infection who have cirrhosis for 12 weeks with this combination....
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...The SVR12 rates in patients infected with genotype 1a were 92% (155/169; 14 relapses) after 8 weeks of sofosbuvir/velpatasvir/voxilaprevir and 99% (170/172; one relapse) after 12 weeks of sofosbuvir/velpatasvir.(71) Thus, the triple combination of sofosbuvir, velpatasvir and voxilaprevir for 8 weeks is not recommended in patients infected with HCV genotype 1a....
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...In POLARIS-2, which included approximately three-quarters of treatment-naïve and one-quarter of treatment-experienced patients and approximately 20% of individuals with cirrhosis, the SVR12 rate was 99% (91/92; no virological failure) after 8 weeks of the triple combination of sofosbuvir, velpatasvir and voxilaprevir.(71) In POLARIS-3, 8 weeks of the triple combination yielded a 96% SVR12 rate (106/110; 2 relapses) in treatment-naïve and treatment-experienced patients with compensated cirrhosis....
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Journal Article•DOI•

EASL recommendations on treatment of hepatitis C: Final update of the series ☆

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Jean-Michel Pawlotsky, Francesco Negro, Alessio Aghemo, Marina Berenguer, Olav Dalgard, Geoffrey Dusheiko, Fiona Marra, Massimo Puoti, Heiner Wedemeyer - Show less +5 more

01 Nov 2020-Journal of Hepatology

TL;DR: These European Association for the Study of the Liver recommendations on treatment of hepatitis C describe the optimal management of patients with recently acquired and chronic HCV infections in 2020 and onwards.

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582 citations

Cites background or methods or result from "Efficacy of 8 Weeks of Sofosbuvir, ..."

...There were only 4 patients with the NS5A Y93H RAS (who all achieved SVR) in this arm.(36) In a randomised controlled trial, genotype 3-infected patients with compensated cirrhosis were assigned to receive sofosbuvir and velpatasvir for 12 weeks, or sofosbuvir and velpatasvir plus ribavirin for 12 weeks....
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...in patients with any NS5A RAS, but only 27/33 (82%) in patients with the Y93H RAS.(36,128,131)...
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...patients receiving the triple combination and 7% and 5% in those receiving sofosbuvir and velpatasvir only in the POLARIS-2 and POLARIS-3 trials, respectively).(36) The proportion of patients who permanently discontinued...
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...%) in patients with the Y93H RAS.36,128,131...
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...In POLARIS-3, 8 weeks of the triple combination yielded a 96% SVR12 rate (106/110; 2 relapses) in treatment-naïve and treatment-experienced patients with compensated cirrhosis.(36) No data with 12 weeks of therapy have been generated in...
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Journal Article•DOI•

Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

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Raymond T. Chung, Marc G. Ghany, Arthur Y. Kim¹, Kristen M. Marks, Susanna Naggie, Hugo E. Vargas, Andrew Aronsohn, Debika Bhattacharya, Tina Broder, Oluwaseun Falade-Nwulia, Robert J. Fontana, Stuart C. Gordon, Theo Heller, Scott D. Holmberg, Ravi Jhaveri, Maureen M. Jonas, Jennifer J. Kiser, Benjamin P. Linas, Vincent Lo Re, Timothy R. Morgan, Ronald Nahass, Marion G. Peters, K. Rajender Reddy, Andrew Reynolds, John D. Scott, Gloria Searson, Tracy Swan, Norah A. Terrault, Stacey Trooskin, John B. Wong, Kimberly A. Workowski - Show less +27 more•Institutions (1)

Harvard University¹

30 Oct 2018-Clinical Infectious Diseases

TL;DR: This update summarizes the latest release of the HCV guidance and focuses on new or amended recommendations since the previous September 2015 print publication.

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Abstract: Recognizing the importance of timely guidance regarding the rapidly evolving field of hepatitis C management, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) developed a web-based process for the expeditious formulation and dissemination of evidence-based recommendations. Launched in 2014, the hepatitis C virus (HCV) guidance website undergoes periodic updates as necessitated by availability of new therapeutic agents and/or research data. A major update was released electronically in September 2017, prompted primarily by approval of new direct-acting antiviral agents and expansion of the guidance's scope. This update summarizes the latest release of the HCV guidance and focuses on new or amended recommendations since the previous September 2015 print publication. The recommendations herein were developed by volunteer hepatology and infectious disease experts representing AASLD and IDSA and have been peer reviewed and approved by each society's governing board.

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480 citations

Journal Article•DOI•

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

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Marc G. Ghany¹, Timothy R. Morgan²•Institutions (2)

National Institutes of Health¹, Veterans Health Administration²

01 Feb 2020-Hepatology

TL;DR: The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) initiated the hepatitis C virus guidance project (hereafter HCV guidance) in 2013 and disseminates up-to-date, peer-reviewed, unbiased, evidence-based recommendations to aid clinicians making decisions regarding the testing, management, and treatment of HCV infection.

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454 citations

Cites background from "Efficacy of 8 Weeks of Sofosbuvir, ..."

...Several well-designed, robust clinical trials have demonstrated the safety(147) and high curative efficacy of glecaprevir/pibrentasvir(148-158) and sofosbuvir/ velpatasvir(159-164) among treatment-naive persons without cirrhosis regardless of HCV genotype....
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...Multiple rigorous clinical trials have demonstrated the safety(139) and high curative efficacy of glecaprevir/pibrentasvir(148,174-177) and sofosbuvir/ velpatasvir(160,162-164,171,178-180) among treatmentnaive adults with compensated cirrhosis, regardless of HCV genotype....
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Journal Article•DOI•

Lancet Seminar – Hepatitis C

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Daniel P. Webster, Paul Klenerman, Geoffrey Dusheiko

21 Mar 2015-The Lancet

TL;DR: Advances in HCV cell culture have enabled improved understanding of HCV virology, which has led to development of many new direct-acting antiviral drugs that target key components of virus replication, allowing for simplified and shortened treatments for HCV that can be given as oral regimens with increased tolerability and efficacy.

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362 citations

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Journal Article•DOI•

Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection

[...]

Jordan J. Feld¹, Ira M. Jacobson², Christophe Hézode³, Tarik Asselah⁴, Peter Ruane⁵, Norbert Gruener⁶, Armand Abergel⁷, Alessandra Mangia⁸, Ching-Lung Lai⁹, Henry Lik Yuen Chan¹⁰, Francesco Mazzotta¹⁰, Christophe Moreno¹⁰, Eric M. Yoshida¹⁰, Stephen D. Shafran¹¹, William J. Towner¹¹, Tram T. Tran¹⁰, John McNally¹⁰, Anu Osinusi¹⁰, Evguenia S. Svarovskaia¹⁰, Yanni Zhu¹⁰, Diana M. Brainard¹⁰, John G. McHutchison¹¹, Kosh Agarwal¹¹, Stefan Zeuzem¹⁰ - Show less +20 more•Institutions (11)

University of British Columbia¹, Cornell University², Paris Diderot University³, Cedars-Sinai Medical Center⁴, Ludwig Maximilian University of Munich⁵, Casa Sollievo della Sofferenza⁶, The Chinese University of Hong Kong⁷, Université libre de Bruxelles⁸, University of Cambridge⁹, University of Toronto¹⁰, Goethe University Frankfurt¹¹

30 Dec 2015-The New England Journal of Medicine

TL;DR: Once-daily sofosbuvir-velpatasvir for 12 weeks provided high rates of sustained virologic response among both previously treated and untreated patients infected with HCV genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis.

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Abstract: BackgroundA simple treatment regimen that is effective in a broad range of patients who are chronically infected with the hepatitis C virus (HCV) remains an unmet medical need. MethodsWe conducted a phase 3, double-blind, placebo-controlled study involving untreated and previously treated patients with chronic HCV genotype 1, 2, 4, 5, or 6 infection, including those with compensated cirrhosis. Patients with HCV genotype 1, 2, 4, or 6 were randomly assigned in a 5:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir in a once-daily, fixed-dose combination tablet or matching placebo for 12 weeks. Because of the low prevalence of genotype 5 in the study regions, patients with genotype 5 did not undergo randomization but were assigned to the sofosbuvir–velpatasvir group. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. ResultsOf the 624 patients who received treatment with sofosbuvir–velpatasvir, 34% had HCV genotype...

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909 citations

Additional excerpts

...Mean age (range), y 53 (18–78) 55 (19–82) 54 (25–75) 55 (31–69) Male 255 (51) 237 (54) 74 (67) 100 (92) Race White 391 (78) 365 (83) 100 (91) 97 (89) Black 48 (10) 47 (11) 0 1 (1) Asian 51 (10) 22 (5) 8 (7) 9 (8) Other 11 (2) 6 (1) 2 (2) 2 (2) Genotype 1a 169 (34) 172 (39) 0 0 1b 63 (13) 59 (13) 0 0 1 other 1 (<1) 1 (<1) 0 0 2 63 (13) 53 (12) 0 0 3 92 (18) 89 (20) 110 (100) 109 (100) 4 63 (13) 57 (13) 0 0 5 18 (4) 0 0 0 6 30 (6) 9 (2) 0 0 Unknown 2 (<1) 0 0 0 Interleukin 28B genotype CC 166 (33) 136 (31) 41 (37) 52 (48) CT 253 (50) 245 (56) 57 (52) 44 (40) TT 82 (16) 59 (13) 12 (11) 13 (12) Mean HCV-RNA level (SD), log10 IU/mL 6....
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...5) Cirrhosis 90 (18) 84 (19) 110 (100) 109 (100) Platelet level < 100 10(3)/mL, n (%) 16 (18) 20 (24) 30 (29) 21 (19) Mean Fibroscan (range), kPa 24 (13–63) 25 (13–72) 23 (13–75) 22 (13–75) Prior HCV treatment experience Treatment-naive 383 (76) 340 (77) 75 (68) 77 (71) Treatment-experienced 118 (24) 100 (23) 35 (32) 32 (29) Pegylated interferon plus ribavirin 93 (79) 81 (81) 31 (89) 30 (94) Other 25 (21) 19 (19) 4 (11) 2 (6) Most recent treatment response Nonresponder 50 (42) 47 (47) 16 (46) 8 (25) Relapse 55 (47) 44 (44) 16 (46) 20 (63) Other 13 (11) 9 (9) 3 (9) 4 (13)...
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Journal Article•DOI•

Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study

[...]

Eric Lawitz¹, Mark S. Sulkowski², Reem Ghalib, Maribel Rodriguez-Torres, Zobair M. Younossi³, Ana Corregidor, Edwin DeJesus, Brian L. Pearlman⁴, Mordechai Rabinovitz⁵, Norman Gitlin, Joseph K. Lim⁶, Paul J. Pockros⁷, John D. Scott⁸, Bart Fevery⁹, Tom Lambrecht, Sivi Ouwerkerk-Mahadevan⁹, Katleen Callewaert⁹, William T. Symonds, Gaston Picchio⁹, Karen L Lindsay⁹, Maria Beumont⁹, Ira M. Jacobson¹⁰ - Show less +18 more•Institutions (10)

University of Texas Health Science Center at San Antonio¹, Johns Hopkins University School of Medicine², Inova Fairfax Hospital³, Atlanta Medical Center⁴, University of Pittsburgh⁵, Yale University⁶, Scripps Health⁷, Harborview Medical Center⁸, Janssen Pharmaceutica⁹, Cornell University¹⁰

15 Nov 2014-The Lancet

TL;DR: Combined simeprevir and sofosbuvir was efficacious and well tolerated in chronic HCV genotype 1 infections and sustained virological response 12 weeks after stopping treatment was achieved.

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793 citations

Additional excerpts

...5) Cirrhosis 90 (18) 84 (19) 110 (100) 109 (100) Platelet level < 100 10(3)/mL, n (%) 16 (18) 20 (24) 30 (29) 21 (19) Mean Fibroscan (range), kPa 24 (13–63) 25 (13–72) 23 (13–75) 22 (13–75) Prior HCV treatment experience Treatment-naive 383 (76) 340 (77) 75 (68) 77 (71) Treatment-experienced 118 (24) 100 (23) 35 (32) 32 (29) Pegylated interferon plus ribavirin 93 (79) 81 (81) 31 (89) 30 (94) Other 25 (21) 19 (19) 4 (11) 2 (6) Most recent treatment response Nonresponder 50 (42) 47 (47) 16 (46) 8 (25) Relapse 55 (47) 44 (44) 16 (46) 20 (63) Other 13 (11) 9 (9) 3 (9) 4 (13)...
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Journal Article•DOI•

Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection

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Graham R. Foster¹, Nezam H. Afdhal¹, Stuart K. Roberts¹, Norbert Bräu², E.J. Gane¹, S. Pianko¹, E.J. Lawitz¹, Alexander J. Thompson¹, Mitchell L. Shiffman¹, Curtis L Cooper¹, William J. Towner¹, Brian Conway¹, Peter Ruane¹, M. Bourliere³, Tarik Asselah¹, Thomas Berg¹, S. Zeuzem¹, William Rosenberg¹, Kosh Agarwal¹, Catherine A.M. Stedman¹, Hongmei Mo¹, Hadas Dvory-Sobol¹, Lingling Han¹, Jing Wang¹, John McNally¹, Anu Osinusi¹, Diana M. Brainard¹, John G. McHutchison¹, Francesco Mazzotta¹, Tram T. Tran¹, Stuart C. Gordon¹, Keyur Patel¹, Nancy Reau¹, Alessandra Mangia¹, Mark S. Sulkowski¹ - Show less +31 more•Institutions (3)

Queen Mary University of London¹, Icahn School of Medicine at Mount Sinai², Duke University³

30 Dec 2015-The New England Journal of Medicine

TL;DR: Among patients with HCV genotype 2 or 3 with or without previous treatment, including those with compensated cirrhosis, 12 weeks of treatment with sofosbuvir-velpatasvir resulted in rates of sustained virologic response that were superior to those with standard treatment withSofosBuvir-ribavirin.

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Abstract: BackgroundIn phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3. MethodsWe conducted two randomized, phase 3, open-label studies involving patients who had received previous treatment for HCV genotype 2 or 3 and those who had not received such treatment, including patients with compensated cirrhosis. In one trial, patients with HCV genotype 2 were randomly assigned in a 1:1 ratio to receive sofosbuvir–velpatasvir, in a once-daily, fixed-dose combination tablet (134 patients), or sofosbuvir plus weight-based ribavirin (132 patients) for 12 weeks. In a second trial, patients with HCV genotype 3 were randomly assigned in a 1:1 ratio to receive sofosbuvir–velpatasvir for 12 weeks (277 patients) or sofosbuvir–ribavirin for 24 weeks (275 patients). The primary end point for the two trials was a sustai...

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730 citations

Journal Article•DOI•

Sofosbuvir, velpatasvir, and voxilaprevir for previously treated HCV infection

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Marc Bourlière, Stuart C. Gordon¹, Steven L. Flamm², Curtis Cooper³, Alnoor Ramji⁴, Myron J. Tong, Natarajan Ravendhran⁵, John M. Vierling⁶, Tram T. Tran⁷, S. Pianko⁸, Meena B. Bansal⁹, Victor de Ledinghen, Robert H. Hyland¹⁰, Luisa M. Stamm¹¹, Hadas Dvory-Sobol¹², Evguenia S. Svarovskaia, Jie Zhang, K.C. Huang, G. Mani Subramanian, Diana M. Brainard, John G. McHutchison, Elizabeth C. Verna, Peter Buggisch, Charles S. Landis, Ziad Younes, Michael P. Curry, Simone I. Strasser, Eugene R. Schiff, K. Rajender Reddy, Michael P. Manns, Kris V. Kowdley, Stefan Zeuzem - Show less +28 more•Institutions (12)

Henry Ford Health System¹, Northwestern University², Ottawa Hospital Research Institute³, Cedars-Sinai Medical Center⁴, Baylor College of Medicine⁵, Royal Prince Alfred Hospital⁶, Icahn School of Medicine at Mount Sinai⁷, Hannover Medical School⁸, University of Washington⁹, Beth Israel Deaconess Medical Center¹⁰, University of Miami¹¹, University of Pennsylvania¹²

31 May 2017-The New England Journal of Medicine

TL;DR: Sofosbuvir‐velpatasvir‐voxilaprevir taken for 12 weeks provided high rates of sustained virologic response among patients across HCV genotypes in whom treatment with a DAA regimen had previously failed.

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Abstract: BackgroundPatients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options MethodsWe conducted two phase 3 trials involving patients who had been previously treated with a DAA-containing regimen In POLARIS-1, patients with HCV genotype 1 infection who had previously received a regimen containing an NS5A inhibitor were randomly assigned in a 1:1 ratio to receive either the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the protease inhibitor voxilaprevir (150 patients) or matching placebo (150 patients) once daily for 12 weeks Patients who were infected with HCV of other genotypes (114 patients) were enrolled in the sofosbuvir–velpatasvir–voxilaprevir group In POLARIS-4, patients with HCV genotype 1, 2, or 3 infection who had previously received a DAA regimen but not an NS5A inhibitor were randomly assigned

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437 citations

Journal Article•DOI•

Direct-acting antivirals for the treatment of hepatitis C virus infection: optimizing current IFN-free treatment and future perspectives.

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Tarik Asselah¹, Nathalie Boyer¹, David Saadoun¹, Michele Martinot-Peignoux¹, Patrick Marcellin¹ - Show less +1 more•Institutions (1)

Paris Diderot University¹

01 Jan 2016-Liver International

TL;DR: Results obtained with oral DAA combinations that have been approved and/or have completed phase 3 clinical trials for HCV infection are summarized and future perspectives are discussed.

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Abstract: There has been a revolution in the treatment of chronic hepatitis C. Several oral regimens combining direct-acting antivirals (DAAs) from different families [NS5B nucleotide inhibitors, NS5B non-nucleoside inhibitors, NS5A replication complex inhibitors and NS3/4A protease inhibitors (PI)] have been developed. These regimens result in an increase in sustained virological response (SVR) rates to above 90% and reduce the duration of treatment to 12 weeks or less. As of 2016 several regimens will be approved with additive potencies, without cross-resistance and with a good safety profile. Remaining issues will include increasing screening and access to care so that HCV may become the first chronic viral infection eradicated worldwide. This review summarizes results obtained with oral DAA combinations that have been approved and/or have completed phase 3 clinical trials for HCV infection and discusses future perspectives.

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199 citations

Additional excerpts

...Subjects experiencing any adverse event, n 361 (72) 303 (69) 83 (75) 81 (74) Discontinuation of treatment owing to adverse event 0 2 (<1) 0 1 (1) Interruption of treatment owing to adverse event 1 (<1) 2 (<1) 1 (1) 0 Serious adverse events 15 (3) 7 (2) 2 (2) 3 (3) Deaths 0 0 1 (1) 0 Common adverse events Headache 134 (27) 99 (23) 27 (25) 32 (29) Fatigue 106 (21) 90 (20) 28 (25) 31 (28) Diarrhea 88 (18) 32 (7) 17 (15) 5 (5) Nausea 80 (16) 40 (9) 23 (21) 10 (9) Asthenia 32 (6) 27 (6) 5 (5) 5 (5) Insomnia 25 (5) 21 (5) 6 (5) 5 (5) Back pain 5 (1) 11 (3) 1 (1) 6 (6) Arthralgia 20 (4) 24 (5) 4 (4) 4 (4) Abdominal pain 22 (4) 7 (2) 9 (8) 5 (5) Upper abdominal pain 18 (4) 9 (2) 2 (2) 7 (6) Muscle spasms 8 (2) 12 (3) 7 (6) 2 (2) Vomiting 16 (3) 8 (2) 7 (6) 1 (1) Myalgia 14 (3) 11 (3) 1 (1) 6 (6) Hematologic event/laboratory event Hemoglobin level <10 g/dL 6 (1) 3 (1) 1 (1) 0 Lymphocytes <500/mm(3) 1 (<1) 3 (1) 3 (3) 1 (1) Neutrophils <750/mm(3) 2 (<1) 2 (<1) 0 1 (1) Platelets <50,000/mm(3) 3 (1) 2 (<1) 1 (1) 1 (1) White blood cell count 1500/mm(3) 0 0 0 1 (1) INR-PT >2....
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...During treatment At 2 wk 330/501 (66) 269/439 (61) 62/110 (56) 55/108 (51) At 4 wk 463/501 (92) 404/439 (92) 96/110 (87) 92/108 (85) At 8 wk 496/500 (99) 438/439 (>99) 107/110 (97) 107/108 (99) After end of treatment At 4 wk 483 (96) 435 (99) 107 (97) 106 (97) At 12 wk (SVR) Overall 476 (95) 432 (98) 106 (96) 105 (96) Genotype 1a 155/169 (92) 170/172 (99) 0 0 Genotype 1b 61/63 (97) 57/59 (97) 0 0 Genotype 1 other 1/1 (100) 1/1 (100) 0 0 Genotype 2 61/63 (97) 53/53 (100) 0 0 Genotype 3 91/92 (99) 86/89 (97) 106/110 (96) 105/109 (96) Genotype 4 58/63 (92) 56/57 (98) 0 0 Genotype 5 17/18 (94) 0 0 0 Genotype 6 30/30 (100) 9/9 (100) 0 0 Unknown 2/2 (100) 0 Virologic breakthrough 0 0 0 0 Virologic rebound 0 0 0 1 (1) Virologic relapse 21 (4) 3 (1) 2 (2) 1 (1) Lost to follow-up evaluation 4 (1) 4 (1) 0 1 (1) Other 0 1 (<1) 2 (2) 1 (1)...
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...Mean age (range), y 53 (18–78) 55 (19–82) 54 (25–75) 55 (31–69) Male 255 (51) 237 (54) 74 (67) 100 (92) Race White 391 (78) 365 (83) 100 (91) 97 (89) Black 48 (10) 47 (11) 0 1 (1) Asian 51 (10) 22 (5) 8 (7) 9 (8) Other 11 (2) 6 (1) 2 (2) 2 (2) Genotype 1a 169 (34) 172 (39) 0 0 1b 63 (13) 59 (13) 0 0 1 other 1 (<1) 1 (<1) 0 0 2 63 (13) 53 (12) 0 0 3 92 (18) 89 (20) 110 (100) 109 (100) 4 63 (13) 57 (13) 0 0 5 18 (4) 0 0 0 6 30 (6) 9 (2) 0 0 Unknown 2 (<1) 0 0 0 Interleukin 28B genotype CC 166 (33) 136 (31) 41 (37) 52 (48) CT 253 (50) 245 (56) 57 (52) 44 (40) TT 82 (16) 59 (13) 12 (11) 13 (12) Mean HCV-RNA level (SD), log10 IU/mL 6....
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