1 Johns Hopkins Hospital, Baltimore, MD, USA.
2 University of California San Francisco, San Francisco, California, USA.
3 University of Washington School of Medicine and Seattle Children's Hospital, Seattle, Washington, USA.
4 The Ohio State University and Nationwide Children's Hospital, Columbus, Ohio, USA.
5 The Royal Children's Hospital, Melbourne, VIC, Australia.
6 Royal Hospital for Children, Glasgow, UK.
7 Texas Liver Institute, San Antonio, Texas, USA.
8 Gilead Sciences Inc, Foster City, California, USA.
9 Digestive Health Institute, Children's Hospital of Colorado and Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Aurora, CO, USA.
10 Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana, USA.
11 Cook Children's Health Care System, Fort Worth, Texas, USA.
12 King's College Hospital, London, UK.
13 Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
For children under 12 years of age who have chronic hepatitis C virus (HCV) infection, there are currently no approved treatments with direct-acting antiviral agents. We therefore evaluated the safety and efficacy of ledipasvir-sofosbuvir in HCV-infected children aged 3 to <6 years old. In an open-label study, patients 3 to <6 years old chronically infected with HCV genotype 1 (n=33) or 4 (n=1) received weight-based doses of combined ledipasvir-sofosbuvir as granules (33.75 mg/150 mg for weights <17 kg or 45 mg/200 mg for weights ≥17 kg) for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). For the first 14 patients, intensive pharmacokinetic sampling was done on day 10 of treatment. All patients had been infected through perinatal transmission and were treatment naïve. No patients had known cirrhosis. Ten patients (29%) weighed <17 kg. SVR12 was achieved in 97% of patients (33/34); the patient who did not achieve SVR12 was 3 years old and discontinued treatment after 5 days because of an adverse event 'abnormal drug taste'. The most common adverse events were vomiting (24% of patients), cough (21%), and pyrexia (21%). No patients experienced a serious adverse event. Intensive pharmacokinetic analysis of 13 patients for whom data were evaluable confirmed that the doses selected were appropriate. CONCLUSIONS: Ledipasvir-sofosbuvir was well tolerated and highly effective in children 3 to <6 years old with chronic HCV infection. This article is protected by copyright. All rights reserved.