An efficacy study of combined oral doses of glecaprevir/pibrentasvir and sofosbuvir for 16 weeks in hepatitis C patients with documented NS5A resistance who did not respond to previous treatment

Direct Acting Antivirals (DAAs) target specific steps in the Hepatitis C (HCV) life cycle and they are most effective when delivered as combination therapies. Cure rates are high for the DAAs funded in New Zealand (95% for VIEKIRA PAK and 98% for MAVIRET). For those who did not respond to these treatments, approximately half will have developed dual resistance to NS5A inhibitors and protease inhibitors. The only appropriate retreatment for these patients who did not respond to prior treatment and have NS5A resistance is with a triple DAA combination comprising of sofosbuvir plus an NS5A inhibitor plus a protease inhibitor. In this study, a regimen with 16 week generic sofosburvir + MAVIRET will be tested to see if it can achieve sustained virologic response in treatment experienced patients with NS5A resistance. Previous Phase II and III studies in other countries have demonstrated >95% cure rates following this regimen. Most participants will be recruited via the doctor or nurse that managed their first (unsuccessful) treatment. The study will involve one screening visit at the participant’s local hospital or clinic during which the participant will consent, have safety blood and other tests to assess eligibility. For example, additional blood tests for NS5A resistance or amount of HCV RNA if not tested previously or the extent of scar tissue in the liver. Once confirmed eligible, MAVIRET will be prescribed via Pharmac and dispensed from a local pharmacy. Generic sofosbuvir will be couriered from Auckland City Hospital to participant’s homes. Participants will attend four weekly visits during treatment where adverse events, concomitant medication and compliance will be reviewed. 12 weeks after the last dose, HCV RNA viral load will be tested to determine if the patient has been cured.