Treatment-Naive Genotype 1b With Compensated Cirrhosis

Recommended and alternative regimens listed by evidence level and alphabetically for:

Treatment-Naive Genotype 1b Patients With Compensated Cirrhosisa 

RECOMMENDED DURATION RATING
Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) 12 weeks I, A
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b 12 weeks I, A
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) 12 weeks I, A
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, A
ALTERNATIVE DURATION RATING
Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) with dasabuvir (600 mg) as part of an extended-release regimen or plus twice-daily dosed dasabuvir (250 mg)c 12 weeks I, A
a For decompensated cirrhosis, please refer to the appropriate section.
b This is a 3-tablet coformulation. Please refer to the prescribing information.
c Please see statement on FDA warning regarding the use of paritaprevir/ritonavir/ombitasvir ± dasabuvir in patients with cirrhosis.

 

For genotype 1b-infected, treatment-naive patients with compensated cirrhosis, there are 4 recommended regimens with comparable efficacy. The alternative regimen is classified as such because, compared to the recommended regimens, it requires a longer duration of treatment, involves greater prescribing complexity, is potentially less efficacious, and/or there are limited supporting data.

Recommended Regimens

Elbasvir/Grazoprevir

The recommendation for use of daily fixed-dose elbasvir (50 mg)/grazoprevir (100 mg) in cirrhotic patients with genotype 1 infection is based on 92 patients (22% of the study cohort) in the phase 3 C-EDGE trial who had Metavir F4 disease (Zeuzem, 2017). SVR12 was 97% in the subgroup of cirrhotic patients. A similar 97% (28/29) SVR12 rate had previously been demonstrated in genotype 1 cirrhotic treatment-naive patients treated with 12 weeks of elbasvir/grazoprevir without ribavirin in the open-label phase 2 C-WORTHY trial, which enrolled both HCV-monoinfected and HIV/HCV-coinfected patients (Lawitz, 2015c). Presence or absence of cirrhosis does not appear to alter the efficacy of the elbasvir/grazoprevir regimen (Lawitz, 2015c); (Zeuzem, 2017).

Glecaprevir/Pibrentasvir

EXPEDITION-1 investigated use of the daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) administered as three 100 mg/40 mg fixed-dose combination pills in DAA-naive (75%) or -experienced (interferon or peginterferon ± ribavirin, or sofosbuvir plus ribavirin ± peginterferon) patients with compensated cirrhosis. Of 146 patients with genotype 1, 2, 4, 5, or 6 given 12 weeks of glecaprevir/pibrentasvir, 145 (99%) achieved SVR12, All G1b patients achieved SVR (Forns, 2017).

EXPEDITION-2, a study of glecaprevir/pibrentasvir in 153 HIV/HCV-coinfected adults with genotype 1, 2, 3, 4, 5, or 6, utilized 8 weeks of treatment for noncirrhotic patients and 12 weeks for cirrhotic patients (the durations since approved by the FDA and recommended in the package insert). The overall SVR12 rate was 98% and there were no observed virologic failures among the 94 patients with genotype 1 infection (Rockstroh, 2017). In EXPEDITION-1 and EXPEDITION-2, neither subtype (1a vs 1b) nor the presence of baseline RASs impacted SVR12 results in DAA-naive genotype 1 patients.

Ledipasvir/Sofosbuvir

The daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) was approved by the FDA for the treatment of genotype 1 infection in treatment-naive patients based on 2 registration trials: ION-1 (865 treatment-naive patients; those with cirrhosis were included) and ION-3 (647 treatment-naive patients; those with cirrhosis were excluded). ION-1 investigated length of treatment (12 weeks vs 24 weeks) and the need for ribavirin (Afdhal, 2014a). SVR12 was 97% to 99% across all study arms with no difference in SVR based on length of treatment, use of ribavirin, or genotype 1 subtype. Sixteen percent of participants enrolled were classified as having cirrhosis. There was no difference in SVR12 rate in those with cirrhosis (97%) versus those without cirrhosis (98%).

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 1 infection in treatment-naive patients based on ASTRAL-1. This placebo-controlled trial involved a 12-week course of sofosbuvir/velpatasvir administered to 624 participants with genotype 1, 2, 4, 5, or 6 who were treatment-naive (n=423) or previously treated with interferon-based therapy, with or without ribavirin or a protease inhibitor (n=201); (Feld, 2015). Of the 328 genotype 1 patients included, 323 achieved SVR with no difference in SVR observed by subtype (98% 1a, 99% 1b). Of 121 participants (all genotypes) classified as having cirrhosis, 120 achieved SVR (99%). Baseline NS5A RASs (at 15% cutoff)—reported in 11% of genotype 1a and 18% of genotype 1b participant samples tested—did not influence SVR rate for genotype 1 (Hézode, 2016). Of the 2 virologic failures in ASTRAL-1 (<1% of treated participants), both were genotype 1 and had baseline RASs. There was no significant difference in the rates of adverse events in the sofosbuvir/velpatasvir vs placebo groups.

The phase 3 POLARIS-2 study randomized 941 DAA-naive patients with genotypes 1, 2, 3, 4, 5, or 6—19% with compensated cirrhosis—to receive either 8 weeks of sofosbuvir (400 mg)/velpatasvir (100 mg)/voxilaprevir (100mg) or 12 weeks of sofosbuvir/velpatasvir (Jacobson, 2017). Of participants treated with sofosbuvir/velpatasvir, 170/172 (99%) with genotype 1a and 57/59 (97%) with genotype 1b achieved SVR with a single relapse observed in each genotype.
 

Alternative Regimen

Paritaprevir/Ritonavir/Ombitasvir + Dasabuvir

The daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) plus twice-daily dosed dasabuvir (250 mg) was approved by the FDA for the treatment of genotype 1b infection in treatment-naive patients based on 3 registration trials: SAPPHIRE-I (151 treatment-naive patients with genotype 1b without cirrhosis); PEARL-III (419 treatment-naive patients with genotype 1b without cirrhosis); and TURQUOISE-II (119 treatment-naive and -experienced patients with genotype 1b and cirrhosis). TURQUOISE-II enrolled treatment-naive and -experienced patients with Child-Turcotte-Pugh class A cirrhosis to receive either 12 weeks or 24 weeks of paritaprevir/ritonavir/ombitasvir + dasabuvir and ribavirin. Overall SVR12 rates were 98.5% in the 12-week arm and 100% in the 24-week arm (Poordad, 2014).

To address the need for ribavirin with this regimen in patients with genotype 1b and cirrhosis, the TURQUOISE-III study evaluated the safety and efficacy of paritaprevir/ritonavir/ombitasvir + dasabuvir without ribavirin for 12 weeks in patients with genotype 1b infection and compensated cirrhosis. Sixty patients (62% men; 55% treatment-experienced; 83% with the IL28B non-CC genotype; 22% with platelet counts <90 x 109/L; 17% with albumin <3.5 g/dL) were enrolled. All patients completed treatment and all achieved SVR12. Based on this study, treating patients with genotype 1b with paritaprevir/ritonavir/ombitasvir + dasabuvir but without ribavirin is recommended, regardless of prior treatment experience or the presence of compensated cirrhosis (Feld, 2016).

Last update: 
September 21, 2017

Additional Reading:    HIV/HCV Coinfection    Renal Impairment    Acute Infection

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