• Massimo Colombo, Alessio Aghemo, Hong Liu, Jie Zhang, Hadas Dvory-Sobol, Robert Hyland, Chohee Yun, Benedetta Massetto, Diana M Brainard, John G McHutchison, Marc Bourlière, Markus Peck-Radosavljevic, Michael Manns, and Stanislas Pol.
• From Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Gilead Sciences, Foster City, California; Hôpital Saint Joseph, Marseilles, and Hôpital Cochin, Paris, France; Medical University of Vienna, Vienna, Austria; and Hannover Medical School, Hannover, Germany.
• Ann. Intern. Med. 2017 Jan 17; 166 (2): 109-117.

BackgroundUse 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.ObjectiveTo 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.DesignRandomized, phase 2, open-label study. (ClinicalTrials.gov: NCT02251717).Setting5 sites in Europe.PatientsTreatment-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.MeasurementsThe primary end point was sustained virologic response at 12 weeks after therapy ended (SVR12).ResultsAmong 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%]).LimitationsThe 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.ConclusionTreatment 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 SourceGilead Sciences.

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