Sofosbuvir and Ribavirin Therapy for Children Aged 3 to <12 Years With Hepatitis C Virus Genotype 2 or 3 Infection

Abstract

Currently, the only approved hepatitis C virus (HCV) treatment for children aged <12 years is pegylated interferon plus ribavirin. In an open‐label study, we evaluated the safety and efficacy of sofosbuvir plus ribavirin for 12 weeks in children aged 3 to <12 years chronically infected with genotype 2 or for 24 weeks in patients with genotype 3. Patients aged 3 to <6 years weighing <17 kg received sofosbuvir 150 mg, and patients aged 3 to <6 years weighing ≥17 kg and all patients aged 6 to <12 years received sofosbuvir 200 mg once daily. Intensive pharmacokinetic sampling conducted in each age group confirmed the appropriateness of sofosbuvir doses. For all patients, ribavirin dosing was determined by baseline weight (up to 1,400 mg/day, two divided doses). The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Fifty‐four patients were enrolled (41 aged 6 to <12 years and 13 aged 3 to <6 years). Most were treatment naïve (98%) and infected perinatally (94%). All but one patient achieved SVR12 (53/54, 98%; 95% confidence interval, 90%‐100%). The patient who did not achieve SVR12 was a 4‐year‐old who discontinued treatment after 3 days because of “abnormal drug taste.” The most commonly reported adverse events in patients aged 6 to <12 years were vomiting (32%) and headache (29%), and those in patients aged 3 to <6 years were vomiting (46%) and diarrhea (39%). One 3‐year‐old patient had a serious adverse event of accidental ribavirin overdose requiring hospitalization for monitoring; this patient completed treatment and achieved SVR12. Conclusion: Sofosbuvir plus ribavirin was well tolerated and highly effective in children aged 3 to <12 years with chronic HCV genotype 2 or 3 infection.

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

“…A 12‐week course is recommended for pediatric patients without cirrhosis, and 24 weeks is recommended for those with compensated cirrhosis (see the online HCV guidance for dosing recommendations). The registration trial conducted in children aged 3 to < 12 years demonstrated an SVR12 of 98% . The use of sofosbuvir plus ribavirin is further supported by clinical trial data involving adolescents and adults with genotype 2 or 3 infection .…”

“…The registration trial conducted in children aged 3 to < 12 years demonstrated an SVR12 of 98%. (286) The use of sofosbuvir plus ribavirin is further supported by clinical trial data involving adolescents (287) and adults with genotype 2 or 3 infection. (288)(289)(290)(291) At the time of manuscript preparation, sofosbuvir (plus ribavirin) remained the only FDA-approved DAA for children 3-11 years with genotype 2 or 3 infection.…”

Systematic review with meta‐analysis: the efficacy and safety of direct‐acting antivirals in children and adolescents with chronic hepatitis C virus infection

“…The US Food and Drug Administration and the European Medicines Agency have recently approved the use of glecaprevir/pibrentasvir for the treatment of HCV in adolescents (12‐17 years of age) and of sofosbuvir/ledipasvir and sofosbuvir plus ribavirin for use in children between 3 and 11 years of age. The evidence to support such approvals has come from open‐label single arm clinical trials 3‐8 . Comparable to the studies that have been conducted in adults, these trials showed that the combinations of DAAs have a high efficacy and an optimal safety profile but have been performed on a limited number of patients.…”

Hepatitis C Virus Treatment in Children: A Challenge for Hepatitis C Virus Elimination

“…Results of the same association are available for 41 children aged 6 to 11 years and for 13 children aged 3 to 5 years (►Table 3). 95 The pharmacokinetic analyses conducted in each age group confirmed the appropriateness of sofosbuvir doses. Of the children, 98% (53/54; 95% CI: 90-100%) achieved SVR12.…”

“…40,81,82 A large phase II and III, open-label, multicenter, multicohort, single-arm study evaluated the safety and the efficacy of sofosbuvir and ribavirin. 94,95 Adolescents Sofosbuvir and ribavirin were used for adolescents (aged between 12 and 17 years or weighing more than 35 kg) with chronic HCV genotype 2 or 3 infection for 12 or 24 weeks, respectively (►Table 3). 94 Pharmacokinetic evaluations of the concentrations of sofosbuvir showed that 400 mg per day provided plasma exposures comparable with those observed in adults from phase II and III studies.…”