Sofosbuvir-Based Treatment Regimens in Patients With HCV
Sofosbuvir-Based Treatment Regimens in Patients With HCV
Due to its high antiviral potency, even when given as monotherapy, the favourable safety profile and obvious lack of cumbersome DDIs, sofosbuvir represents a nearly ideal backbone for the treatment of patients who were up to now considered as difficult-to-treat, that is, patients with prior treatment failures to Peg-IFNα-based treatments (including those who failed triple therapy), patients being intolerant or ineligible to Peg-IFNα, patients with extra hepatic HCV manifestations or HCV/HIV co-infection, as well as those with decompensated cirrhosis or liver transplant recipients.
Pilot studies in patients awaiting LT and in liver transplant recipients with aggressive HCV recurrence are currently ongoing to assess efficacy of sofosbuvir in this population (studies NCT01687270 and NCT01779518; for more information see: http://www.clinicaltrials.gov). Sofosbuvir plus daclatasvir combination proof-of-concept therapy was effective to cure a liver transplant recipient with severe recurrent cholestatic hepatitis C. Preventing the infection of the graft by application of sofosbuvir either alone or in combination with a second DAA also appears to become a realistic scenario in the near future.
Treatment efficacy of IFNα-free sofosbuvir regimens in HCV type 1-infected patients with compensated cirrhosis has not been evaluated in a significant number of patients. However, a lower cure rate might be expected given the fact that in HCV type 2 and especially in type 3-infected patients cirrhosis was one of the main risk factors for reduced SVR rates (figure 4). The expected low SVR in these patients has influenced the design of the NCT01687257 in which patients infected with different HCV types who have compensated or decompensated liver cirrhosis receive an extended 48-week combined treatment of sofosbuvir plus RBV. One is inclined to argue that patients with decompensated HCV-induced cirrhosis may profit most from IFNα-free combinations with different DAAs. In some ongoing trials evaluating these treatments, patients with liver cirrhosis may be included; however, data on safety and efficacy are awaited.
Sofosbuvir is currently being investigated in patients with HCV/HIV co-infection in the PHOTON trial (NCT01783678). In this trial, the efficacy of the combination of sofosbuvir plus RBV is investigated over 12 weeks in HCV type 2-infected patients and for 24 weeks in HCV type 1, 2, 3 and 4-infected patients.
Sofosbuvir for Difficult-to-Treat Patients
Due to its high antiviral potency, even when given as monotherapy, the favourable safety profile and obvious lack of cumbersome DDIs, sofosbuvir represents a nearly ideal backbone for the treatment of patients who were up to now considered as difficult-to-treat, that is, patients with prior treatment failures to Peg-IFNα-based treatments (including those who failed triple therapy), patients being intolerant or ineligible to Peg-IFNα, patients with extra hepatic HCV manifestations or HCV/HIV co-infection, as well as those with decompensated cirrhosis or liver transplant recipients.
Pilot studies in patients awaiting LT and in liver transplant recipients with aggressive HCV recurrence are currently ongoing to assess efficacy of sofosbuvir in this population (studies NCT01687270 and NCT01779518; for more information see: http://www.clinicaltrials.gov). Sofosbuvir plus daclatasvir combination proof-of-concept therapy was effective to cure a liver transplant recipient with severe recurrent cholestatic hepatitis C. Preventing the infection of the graft by application of sofosbuvir either alone or in combination with a second DAA also appears to become a realistic scenario in the near future.
Treatment efficacy of IFNα-free sofosbuvir regimens in HCV type 1-infected patients with compensated cirrhosis has not been evaluated in a significant number of patients. However, a lower cure rate might be expected given the fact that in HCV type 2 and especially in type 3-infected patients cirrhosis was one of the main risk factors for reduced SVR rates (figure 4). The expected low SVR in these patients has influenced the design of the NCT01687257 in which patients infected with different HCV types who have compensated or decompensated liver cirrhosis receive an extended 48-week combined treatment of sofosbuvir plus RBV. One is inclined to argue that patients with decompensated HCV-induced cirrhosis may profit most from IFNα-free combinations with different DAAs. In some ongoing trials evaluating these treatments, patients with liver cirrhosis may be included; however, data on safety and efficacy are awaited.
Sofosbuvir is currently being investigated in patients with HCV/HIV co-infection in the PHOTON trial (NCT01783678). In this trial, the efficacy of the combination of sofosbuvir plus RBV is investigated over 12 weeks in HCV type 2-infected patients and for 24 weeks in HCV type 1, 2, 3 and 4-infected patients.
