NS5A Inhibitor DAA-Experienced Genotype 1 Patients

Recommended and alternative regimens for:

NS5A Inhibitor DAA-Experienced, Genotype 1 Patients With or Without Compensated Cirrhosisa

Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)/voxilaprevir (100mg) 12 weeks I, A
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b except NS3/4 protease inhibitor inclusive DAA combination regimens 16 weeks IIa, B
a For decompensated cirrhosis, please refer to the appropriate section.
​b This is a 3-tablet coformulation. Please refer to the prescribing information.


Recommended Regimen


The placebo-controlled, phase 3 POLARIS-1 trial evaluated a 12-week course of the daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)/voxilaprevir (100mg) in patients with a prior NS5A inhibitor-containing DAA regimen. The majority (61%) experienced a failure with a combination regimen of an NS5B inhibitor plus an NS5A inhibitor, such as sofosbuvir/ledipasvir (Bourliere, 2017). The overall SVR12 rate was 97% (146/150) in genotype 1-infected patients. SVR12 rates were 96% (97/101) for participants with genotype 1a infection and 100% (45/45) for those with genotype 1b infection. A single genotype 1-infected patient experienced relapse; this individual had subtype 1a infection and cirrhosis. Baseline RASs and the presence of cirrhosis were not significant predictors of virologic failure in genotype 1 infection. Serious adverse events were similar between the placebo and treatment arms; only 1 patient discontinued therapy due to an adverse event. Headache, diarrhea, and nausea were more common in those patients receiving sofosbuvir/velpatasvir/voxilaprevir compared to placebo.

Alternative Regimen


In parts 1 and 2 of the MAGELLAN-1 trial, 42 genotype 1-infected patients had previously been treated with either an NS5A inhibitor or an NS3/4A protease inhibitor (Poordad, 2017); (Poordad, 2017b). Twenty-four percent of these patients had cirrhosis and 79% were genotype 1a infected. Patients who were previously treated with an NS5A inhibitor (ledipasvir or daclatasvir) and not concomitantly treated with a NS3/4A protease inhibitor were retreated 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 16 weeks. Among these patients, 94% (16/17) achieved SVR 12. The single patient who did not respond to therapy had an on-treatment virologic failure. Due to the 16-week duration of therapy and limited supporting data, this is recommended as an alternative regimen.

Last update: 
September 21, 2017