BACKGROUND: Use of interferon and ribavirin to treat chronic hepatitis C virus (HCV) infection in kidney transplant recipients is limited because of the risk for allograft rejection and poor tolerability. OBJECTIVE: To evaluate the safety and efficacy of the interferon- and ribavirin-free regimen ledipasvir-sofosbuvir in kidney transplant recipients with chronic genotype 1 or 4 HCV infection. DESIGN: Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT02251717). SETTING: 5 sites in Europe. PATIENTS: Treatment-naive or -experienced kidney transplant recipients with chronic genotype 1 or 4 HCV infection, with or without compensated cirrhosis, and with an estimated glomerular filtration rate (eGFR) of 40 mL/min or greater were randomly assigned 1:1 to receive ledipasvir (90 mg) and sofosbuvir (400 mg) for 12 or 24 weeks. MEASUREMENTS: The primary end point was sustained virologic response at 12 weeks after therapy ended (SVR12). RESULTS: Among 114 patients, the median age was 53 years, 58% were male, 91% had genotype 1 infection, 69% were treatment naive, and 15% had compensated cirrhosis. The median eGFR was 56 mL/min (range, 35 to 135 mL/min). One hundred percent of patients (57 of 57) treated for 12 weeks (95% CI, 94% to 100%) and 100% of those (57 of 57) treated for 24 weeks (CI, 94% to 100%) achieved SVR12. Serious adverse events were reported in 13 patients (11%). Of these, 3 events-syncope, pulmonary embolism, and serum creatinine increase-in 3 patients were determined to be treatment related. One patient permanently discontinued treatment because of an adverse event (syncope). The most frequent adverse events overall were headache (n = 22 [19%]), asthenia (n = 16 [14%]), and fatigue (n = 11 [10%]). LIMITATIONS: The study was open label, no inferential statistics were planned, and only patients with genotype 1 or 4 infection were included. Few patients with HCV genotype 1a and cirrhosis were enrolled. CONCLUSION: Treatment with ledipasvir-sofosbuvir for 12 or 24 weeks was well-tolerated and seemed to have an acceptable safety profile among kidney transplant recipients with HCV genotype 1 or 4 infection, all of whom achieved SVR12. PRIMARY FUNDING SOURCE: Gilead Sciences.
BACKGROUND: Use of interferon and ribavirin to treat chronic hepatitis C virus (HCV) infection in kidney transplant recipients is limited because of the risk for allograft rejection and poor tolerability. OBJECTIVE: To evaluate the safety and efficacy of the interferon- and ribavirin-free regimen ledipasvir-sofosbuvir in kidney transplant recipients with chronic genotype 1 or 4 HCV infection. DESIGN: Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT02251717). SETTING: 5 sites in Europe. PATIENTS: Treatment-naive or -experienced kidney transplant recipients with chronic genotype 1 or 4 HCV infection, with or without compensated cirrhosis, and with an estimated glomerular filtration rate (eGFR) of 40 mL/min or greater were randomly assigned 1:1 to receive ledipasvir (90 mg) and sofosbuvir (400 mg) for 12 or 24 weeks. MEASUREMENTS: The primary end point was sustained virologic response at 12 weeks after therapy ended (SVR12). RESULTS: Among 114 patients, the median age was 53 years, 58% were male, 91% had genotype 1 infection, 69% were treatment naive, and 15% had compensated cirrhosis. The median eGFR was 56 mL/min (range, 35 to 135 mL/min). One hundred percent of patients (57 of 57) treated for 12 weeks (95% CI, 94% to 100%) and 100% of those (57 of 57) treated for 24 weeks (CI, 94% to 100%) achieved SVR12. Serious adverse events were reported in 13 patients (11%). Of these, 3 events-syncope, pulmonary embolism, and serum creatinine increase-in 3 patients were determined to be treatment related. One patient permanently discontinued treatment because of an adverse event (syncope). The most frequent adverse events overall were headache (n = 22 [19%]), asthenia (n = 16 [14%]), and fatigue (n = 11 [10%]). LIMITATIONS: The study was open label, no inferential statistics were planned, and only patients with genotype 1 or 4 infection were included. Few patients with HCV genotype 1a and cirrhosis were enrolled. CONCLUSION: Treatment with ledipasvir-sofosbuvir for 12 or 24 weeks was well-tolerated and seemed to have an acceptable safety profile among kidney transplant recipients with HCV genotype 1 or 4 infection, all of whom achieved SVR12. PRIMARY FUNDING SOURCE: Gilead Sciences.
Authors: Sarah E Van Pilsum Rasmussen; Shanti Seaman; Diane Brown; Niraj Desai; Mark Sulkowski; Dorry L Segev; Christine M Durand; Jeremy Sugarman Journal: AJOB Empir Bioeth Date: 2019-10-16
Authors: Massimo Andreoni; Sergio Babudieri; Savino Bruno; Massimo Colombo; Anna L Zignego; Vito Di Marco; Giovanni Di Perri; Carlo F Perno; Massimo Puoti; Gloria Taliani; Erica Villa; Antonio Craxì Journal: Infection Date: 2017-11-02 Impact factor: 3.553
Authors: D A Axelrod; M A Schnitzler; T Alhamad; F Gordon; R D Bloom; G P Hess; H Xiao; M Nazzal; D L Segev; V R Dharnidharka; A S Naik; N N Lam; R Ouseph; B L Kasiske; C M Durand; K L Lentine Journal: Am J Transplant Date: 2018-05-29 Impact factor: 8.086
Authors: Mary G Bowring; Lauren M Kucirka; Allan B Massie; Tanveen Ishaque; Sunjae Bae; Ashton A Shaffer; Jacqueline Garonzik Wang; Mark Sulkowski; Niraj Desai; Dorry L Segev; Christine M Durand Journal: Transplantation Date: 2018-12 Impact factor: 4.939