Table 1.
Characteristics of contemporary hepatitis C treatment regimens
| Drug regimen | Paritaprevir/ritonavir/ombitasvir/dasabuvir | Ledipasvir/sofosbuvir | Simeprevir/sofosbuvir | Daclatasvir/sofosbuvir | Grazoprevir/elbasvir |
|---|---|---|---|---|---|
| Drug classes | NS3/4A protease inhibitor/CYP3A pharmacoenhancing agent/NS5A inhibitor/non-nucleoside NS5B palm polymerase inhibitor | NS5A protein inhibitor/NS5B polymerase inhibitor | NS3/A4 protease inhibitor/NS5B polymerase inhibitor | NS5A inhibitor/NS5B polymerase inhibitor | NS3/4A protease inhibitor/NS5A replication complex inhibitor |
| Efficacy | |||||
| Genotypes | 1 | 1, 4, 5, 6 | 1 | 1, 2, 3 | 1, 4 |
| Treatment-naïve non-cirrhotics | SVR = 96–97% |
GT 1 SVR = 94–99% GT 4, 5, or 6 SVR = 93–96% |
SVR = 93% |
GT1 SVR = 96% GT3 SVR = 97% |
GT1a SVR = 92% GT1b SVR = 99% |
| Treatment-naïve cirrhotics |
GT1a SVR = 92% GT1b SVR = 100% |
GT 1 SVR = 94% GT 4, 5, or 6 SVR = 93–96% |
SVR = 95% | GT3 SVR = 58% | SVR = 97% |
| Treatment experienced non-cirrhotics |
GT1a SVR = 96% GT1b SVR = 100% |
GT 1 SVR = 95% GT 4, 5, or 6 SVR = 93–96% |
SVR = 93% | GT3 SVR = 91–100% | SVR = 94% |
| Treatment experienced cirrhotics |
GT1a SVR = 80–100% GT1b SVR = 86–100% |
GT 1 SVR = 86–100% GT 4, 5, or 6 SVR = 93–96% |
SVR = 86% (12 weeks) SVR = 100% (24 weeks) |
GT3 SVR = 86% | SVR = 95% |
| HIV coinfection |
GT1a SVR = 91% GT1b SVR = 100% |
GT 1 or 4 SVR = 96% | SVR = 77% from observational effectiveness study |
GT 1 no cirrhosis SVR = 98% GT 1 cirrhosis SVR = 91% GT3 SVR = 100% |
SVR = 96% |
| Convenience | |||||
| Dosing | Two tablets daily (75/50/12.5 mg) and 250 mg tablet twice daily | One tablet daily (90 mg/400 mg) | 150 mg daily/400 mg daily |
60 mg daily/400 mg daily With strong CYP3A inhibitors—30 mg daily of daclatasvir With moderate CYP3A inducers—90 mg daily of daclatasvir |
100 mg/50 mg daily |
| Food requirement | With food | With or without food | With food | With or without food | With or without food |
| Need for ribavirin | Use ribavirin except in non-cirrhotic GT1B patients | Can be considered in treatment experienced GT 1 patients with cirrhosis who are eligible or patients with decompensated cirrhosis | No | Can be considered in presence of cirrhosis | Use ribavirin if baseline NS5A resistance-associated variants |
| Duration | 12 weeks, except for GT1a with cirrhosis is 24 weeks |
Treatment naïve without cirrhosis and baseline HCV RNA <6 million GT1 = 8 weeks Treatment naive with or without cirrhosis GT 1, 4, 5 or 6 = 12 weeks Treatment experienced without cirrhosis GT 1, 4, 5 or 6 = 12 weeks Treatment experienced with compensated cirrhosis GT 1 = 24 weeks or 12 weeks with ribavirin GT 4, 5, 6 = 12 weeks Decompensated cirrhosis GT 1 or 4 = 12 weeks |
Treatment naive or experienced without cirrhosis 12 weeks Treatment naive or experienced with cirrhosis 24 weeks |
12 weeks Cirrhosis: GT1: 24 weeks GT2: 16–24 weeks GT3: 24 weeks |
12 weeks 16 weeks in the presence of NS5A resistance-associated variants |
| Single tablet regimen | No (first 3 drugs are a combination tablet in addition to dasabuvir tablets) | Yes | No | No | Yes |
| Safety | |||||
| Adverse events |
Common-fatigue, nausea, pruritus, skin reactions, insomnia, asthenia Hepatic decompensation and heart failure in patients with cirrhosis Increased risk of ALT elevations |
Common-fatigue, headache, nausea, diarrhea, insomnia Serious symptomatic bradycardia when coadministered amiodarone If administered with RBV-diarrhea, N/V, loss of appetite, asthenia, neutropenia, dizziness, hemolytic anemia (serious) |
Common-fatigue, headache, nausea Serious symptomatic bradycardia when the combo is administered with amiodarone Hepatic decompensation and heart failure have also been seen in patients with advanced or decompensated cirrhosis Photosensitivity and rash |
Common-fatigue, nausea, headache, diarrhea Serious symptomatic bradycardia when the combo is administered with amiodarone |
Common-fatigue, headache, nausea With ribavirin—anemia and headache Serious—ALT elevations |
| Special notes | Numerous drug interactions due to ritonavir component | No dosage recommendation can be given for patients with severe renal impairment (CrCl <30 mL/min) or with ESRD due to high exposures of sofosbuvir metabolite | Safety and efficacy has not been established with sofosbuvir in patients with CrCl <30 ml/min or patients on hemodialysis |
Safety and efficacy has not been established with sofosbuvir in patients with CrCl <30 ml/min or patients on hemodialysis Dose of daclatasvir may need to be altered when concomitantly used with other CYP3A inhibitors or inducers |
Can be used in chronic kidney disease (CKD) stages 4 and 5, including patients on hemodialysis |