Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection

被引：663

作者：

Foster, G. R. ^{[1
]}

Afdhal, N. ^{[5
]}

Roberts, S. K. ^{[6
,7
]}

Braeu, N. ^{[11
,12
]}

Gane, E. J. ^{[13
]}

Pianko, S. ^{[9
,10
]}

Lawitz, E. ^{[15
]}

Thompson, A. ^{[8
]}

Shiffman, M. L. ^{[16
]}

Cooper, C. ^{[17
]}

Towner, W. J. ^{[19
]}

Conway, B. ^{[18
]}

Ruane, P. ^{[20
]}

Bourliere, M. ^{[23
]}

Asselah, T. ^{[24
]}

Berg, T. ^{[22
,25
]}

Zeuzem, S. ^{[26
]}

Rosenberg, W. ^{[2
,3
]}

Agarwal, K. ^{[4
]}

Stedman, C. A. M. ^{[14
]}

Mo, H. ^{[22
]}

Dvory-Sobol, H. ^{[22
]}

Han, L. ^{[22
]}

Wang, J. ^{[22
]}

McNally, J. ^{[22
]}

Osinusi, A. ^{[22
]}

Brainard, D. M. ^{[22
]}

McHutchison, J. G. ^{[22
]}

Mazzotta, F. ^{[27
]}

Tran, T. T. ^{[21
]}

Gordon, S. C. ^{[29
]}

Patel, K. ^{[30
]}

Reau, N. ^{[31
]}

Mangia, A. ^{[28
]}

Sulkowski, M. ^{[32
]}

机构：

[1] Queen Mary Univ London, London E1 4AT, England

[2] UCL, London WC1E 6BT, England

[3] Kings Coll Hosp London, London SE5 8RX, England

[4] Inst Liver Studies, London, England

[5] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

[6] Alfred Hlth, Melbourne, Vic, Australia

[7] Monash Univ, Melbourne, Vic 3004, Australia

[8] St Vincents Hosp, Melbourne, Vic, Australia

[9] Monash Hlth, Clayton, Vic, Australia

[10] Monash Univ, Clayton, Vic, Australia

[11] James J Peters Vet Affairs Med Ctr, Bronx, NY USA

[12] Icahn Sch Med Mt Sinai, New York, NY 10029 USA

[13] Auckland Clin Studies, Auckland, New Zealand

[14] Christchurch Clin Studies Trust & Univ Otago, Christchurch, New Zealand

[15] Univ Texas Hlth Sci Ctr San Antonio, Texas Liver Inst, San Antonio, TX 78229 USA

[16] Liver Inst Virginia, Richmond, VA USA

[17] Univ Ottawa, Ottawa, ON, Canada

[18] Vancouver Infect Dis Ctr, Vancouver, BC, Canada

[19] Kaiser Permanente, Los Angeles, CA USA

[20] Ruane Med, Los Angeles, CA USA

[21] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA

[22] Gilead Sci Inc, Foster City, CA 94404 USA

[23] Hop St Joseph, Marseille, France

[24] Univ Paris Diderot, INSERM, UMR 1149, Hop Beaujon,Serv Hepatol, Clichy, France

[25] Univ Hosp Leipzig, Leipzig, Germany

[26] Goethe Univ Frankfurt, D-60054 Frankfurt, Germany

[27] Santa Maria Annunziata Hosp, Florence, Italy

[28] Casa Sollievo Sofferenza Hosp, San Giovanni Rotondo, Italy

[29] Henry Ford Hlth Syst, Detroit, MI USA

[30] Duke Univ, Sch Med, Durham, NC USA

[31] Rush Univ, Med Ctr, Chicago, IL 60612 USA

[32] Johns Hopkins Univ, Baltimore, MD USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2015年 / 373卷 / 27期

关键词：

C VIRUS-INFECTION;

D O I：

10.1056/NEJMoa1512612

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND In 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. METHODS We 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 sustained virologic response at 12 weeks after the end of therapy. RESULTS Among patients with HCV genotype 2, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 99% (95% confidence interval [CI], 96 to 100), which was superior to the rate of 94% (95% CI, 88 to 97) in the sofosbuvir-ribavirin group (P = 0.02). Among patients with HCV genotype 3, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 95% (95% CI, 92 to 98), which was superior to the rate of 80% (95% CI, 75 to 85) in the sofosbuvir-ribavirin group (P<0.001). The most common adverse events in the two studies were fatigue, headache, nausea, and insomnia. CONCLUSIONS 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 with sofosbuvir-ribavirin.

引用

页码：2608 / 2617

页数：10

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