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Recommended regimens listed by evidence level and alphabetically for:Treatment-Naive Persons With Genotype 2 Infection With Compensated Cirrhosisa |
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| RECOMMENDED | DURATION | RATING  |
| Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) | 12 weeks | I, A |
| Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b | 8 weeks | I, B |
| a For decompensated cirrhosis, please refer to the appropriate section. b Dosing is 3 coformulated tablets (glecaprevir [100 mg]/pibrentasvir [40 mg]) taken once daily. Please refer to the prescribing information. |
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Recommended Regimens
Sofosbuvir/Velpatasvir
The daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) for 12 weeks was approved by the FDA for the treatment of genotype 2 infection in persons without cirrhosis or with compensated cirrhosis. ASTRAL-2 compared 12 weeks of sofosbuvir/velpatasvir to 12 weeks of sofosbuvir plus ribavirin in 266 treatment-naive and treatment-experienced persons without cirrhosis or with compensated cirrhosis. The study showed superior efficacy of sofosbuvir/velpatasvir compared with sofosbuvir plus ribavirin (SVR12 rates of 99% versus 94%); (Foster, 2015a). ASTRAL-1 also included 104 treatment-naive and treatment-experienced participants with genotype 2 infection without cirrhosis or with compensated cirrhosis, all of whom achieved SVR12 (Feld, 2015).
Pooled analysis of all genotype 2 participants in ASTRAL-1 and ASTRAL-2 demonstrated 100% (29/29) SVR12 rate in those with compensated cirrhosis and 99% (194/195) SVR12 rate in treatment-naive participants. Among participants with genotype 2 infection receiving sofosbuvir/velpatasvir, the presence of baseline NS5A or NS5B RASs was not associated with virologic failure (Asselah, 2018).
The POLARIS-2 phase 3 study randomized DAA-naive participants to 8 weeks of sofosbuvir (400 mg)/velpatasvir (100 mg)/voxilaprevir (100mg) versus 12 weeks of sofosbuvir/velpatasvir. Fifty-three persons with genotype 2 infection were included in the sofosbuvir/velpatasvir arm and all achieved SVR12 (100%). This study confirms the high efficacy and safety of this 12-week regimen in persons with genotype 2 infection (Jacobson, 2017). A real-world, pooled analysis of 12 cohort studies demonstrated an SVR rate of 98.5% (266/270) among adults with genotype 2 infection and compensated cirrhosis who were treated with 12 weeks of sofosbuvir/velpatasvir (Mangia, 2020).
Glecaprevir/Pibrentasvir
EXPEDITION-1 was a multicenter, open-label, single-arm, phase 3 trial that enrolled 146 treatment-naive or treatment-experienced persons (interferon or peginterferon ± ribavirin, or sofosbuvir plus ribavirin ± peginterferon) with genotype 1, 2, 4, 5, or 6 infection and compensated cirrhosis. Participants were treated with the daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) administered as three 100 mg/40 mg fixed-dose combination pills for 12 weeks. Across all genotypes, 99%(145/146) achieved SVR12 (Forns, 2017). EXPEDITION-1 included 31 treatment-naive and treatment-experienced persons with genotype 2 infection and compensated cirrhosis; all achieved SVR12. Baseline NS5A RASs were detected (by next-generation sequencing using a 15% detection cutoff) in 40% of 133 tested participants. Baseline NS5A RASs had no effect on SVR rates among treatment-naive and treatment-experienced persons with genotype 2 infection.
EXPEDITION-8 evaluated glecaprevir/pibrentasvir for a reduced duration of 8 weeks in treatment-naive participants with compensated cirrhosis and genotype 1, 2 (n=26), 4, 5 or 6 infection. People with a prior history of decompensation, hepatocellular carcinoma, and HIV or HBV coinfection were excluded from this study. SVR12 rate was 100% (26/26) among participants with genotype 2 infection with no virologic failures (Brown, 2020). Real-world data support the use of an 8-week course of glecaprevir/pibrentasvir in persons with compensated cirrhosis (Flamm, 2020).