Download Full GuidancePage Retired 1/21/2021
Recommended regimens listed by evidence level and alphabetically for:
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| RECOMMENDED | DURATION |
RATING 
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| Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b for patients without cirrhosis | 8 weeks | IIa, B |
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| Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b for patients with compensated cirrhosis | 12 weeks | I, B |
| Daily fixed-dose combination ledipasvir (90 mg)/sofosbuvir (400 mg) | 12 weeks | IIa, B |
| Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) | 12 weeks | IIa, B |
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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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Glecaprevir/Pibrentasvir
A combined analysis of the daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) administered as three 100 mg/40 mg fixed-dose combination pills for 8 weeks or 12 weeks among 2,041 patients participating in phase 2 and phase 3 clinical trials included 30 patients with genotype 5 and 44 with genotype 6 (Puoti, 2018). Approximately 22% of patients in the overall study had a prior interferon-based treatment failure; DAA failures other than with sofosbuvir were excluded. No patients had cirrhosis. SVR rates among treatment-naive or -experienced, genotype 5 participants were 100% (2/2) for those receiving 8 weeks of glecaprevir/pibrentasvir and 100% (28/28) for those receiving 12 weeks of glecaprevir/pibrentasvir. SVR rates among treatment-naive or -experienced, genotype 6 participants were 92% (12/13) for those receiving 8 weeks of glecaprevir/pibrentasvir and 100% (31/31) among those receiving 12 weeks of glecaprevir/pibrentasvir. The single treatment failure in the 8-week group was a nonvirologic failure.
Ledipasvir/Sofosbuvir
Ledipasvir has in vitro activity against most genotype 6 subtypes, except 6e (Wong, 2013); (Kohler, 2014). A small, 2-center, open-label study (NCT01826981) investigated the safety and efficacy of a 12-week course of the daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) in treatment-naive or -experienced patients with genotype 6. Twenty-five patients (92% treatment naive) who were primarily of Asian descent (88%) were infected with different genotype 6 subtypes (n=8 6a; n=6 6e; n=3 6l; n=2 6m; n=3 6p; n=2 6q; n=1 6r). Two patients (8%) had compensated cirrhosis. The SVR12 was 96% (24/25). The single patient who experienced relapse had discontinued therapy at week 8 because of drug use. No patient discontinued treatment due to adverse events (Gane, 2015).
Similarly, 41 patients with genotype 5 were treated with 12 weeks of ledipasvir/sofosbuvir. The group included both treatment-naive and -experienced patients, with and without cirrhosis. SVR was 93% (38/41) (Abergel, 2016).
Sofosbuvir/Velpatasvir
Velpatasvir has in vitro activity against genotypes 5 and 6. The ASTRAL-1 study included 35 patients with genotype 5 and 41 patients with genotype 6. Among those participants, only 11 and 3, respectively, were treatment experienced (Feld, 2015). All genotype 5 and 6, treatment-experienced patients treated with 12 weeks of sofosbuvir (400 mg)/velpatasvir (100 mg) achieved SVR12.