title: Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection.
abstract: 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. (Funded by Gilead Sciences; ASTRAL-2 ClinicalTrials.gov number, NCT02220998; and ASTRAL-3, NCT02201953.).
authors.affiliation: From Queen Mary University of London (G.R.F.), University College London (W.R.), King's College Hospital (W.R.), and Institute of Liver Studies (K.A.) - all in London; Beth Israel Deaconess Medical Center, Boston (N.A.); Alfred Health and Monash University (S.K.R.) and St. Vincent's Hospital (A.T.), Melbourne, VIC, and Monash Health and Monash University, Clayton, VIC (S.P.) - all in Australia; James J. Peters Veterans Affairs Medical Center, Bronx (N.B.), and Icahn School of Medicine at Mount Sinai, New York (N.B.) - both in New York; Auckland Clinical Studies, Auckland (E.J.G.), and Christchurch Clinical Studies Trust and University of Otago, Christchurch (C.A.M.S.) - both in New Zealand; Texas Liver Institute, University of Texas Health Science Center, San Antonio (E.L.); Liver Institute of Virginia, Richmond (M.L.S.); University of Ottawa, Ottawa (C.C.), and Vancouver Infectious Diseases Centre, Vancouver, BC (B.C.) - both in Canada; Kaiser Permanente (W.J.T.), Ruane Medical (P.R.), and Cedars-Sinai Medical Center (T.T.T.), Los Angeles, and Gilead Sciences, Foster City (H.M., H.D.-S., L.H., J.W., J.M., A.O., D.M.B., J.G.M.) - all in California; Hôpital Saint Joseph, Marseilles (M.B.), and Service d'Hépatologie, Hôpital Beaujon, INSERM UMR 1149, Université Paris Diderot, Clichy (T.A.) - both in France; University Hospital Leipzig, Leipzig (T.B.), and Johann Wolfgang Goethe University, Frankfurt (S.Z.) - both in Germany; Santa Maria Annunziata Hospital, Florence (F.M.), and Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (A.M.) - both in Italy; Henry Ford Health System, Detroit (S.C.G.); Duke University School of Medicine, Durham, NC (K.P.); Rush University Medical Center, Chicago (N.R.); and Johns Hopkins University, Baltimore (M.S.).
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.forename: Nezam
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authors.lastname: Afdhal
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Roberts
authors.forename: Norbert
authors.initials: N
authors.lastname: Bräu
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gane
authors.forename: Stephen
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authors.lastname: Pianko
authors.forename: Eric
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authors.lastname: Lawitz
authors.forename: Alex
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authors.lastname: Thompson
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.forename: William J
authors.initials: WJ
authors.lastname: Towner
authors.forename: Brian
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authors.lastname: Conway
authors.forename: Peter
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authors.lastname: Ruane
authors.forename: Marc
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authors.lastname: Bourlière
authors.forename: Tarik
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authors.lastname: Asselah
authors.forename: Thomas
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authors.lastname: Berg
authors.forename: Stefan
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authors.lastname: Zeuzem
authors.forename: William
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authors.lastname: Rosenberg
authors.forename: Kosh
authors.initials: K
authors.lastname: Agarwal
authors.forename: Catherine A M
authors.initials: CA
authors.lastname: Stedman
authors.forename: Hongmei
authors.initials: H
authors.lastname: Mo
authors.forename: Hadas
authors.initials: H
authors.lastname: Dvory-Sobol
authors.forename: Lingling
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authors.lastname: Han
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: McNally
authors.forename: Anu
authors.initials: A
authors.lastname: Osinusi
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.forename: Francesco
authors.initials: F
authors.lastname: Mazzotta
authors.forename: Tram T
authors.initials: TT
authors.lastname: Tran
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Gordon
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
authors.forename: Nancy
authors.initials: N
authors.lastname: Reau
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.forename: Mark
authors.initials: M
authors.lastname: Sulkowski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates / Q000009:adverse effects / Q000627:therapeutic use*; D004338:Drug Combinations; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D000069474:Sofosbuvir / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D055815:Young Adult; D012324:RNA-Dependent RNA Polymerase; D001562:Benzimidazoles; D001578:Benzopyrans
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D004338:Drug Combinations; D006576:Heterocyclic Compounds, 4 or More Rings; D000069474:Sofosbuvir; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C000604171:velpatasvir; D001562:Benzimidazoles; D001578:Benzopyrans