RESUMEN
BACKGROUND & AIMS: Mathematical modeling of viral kinetics has been shown to identify patients with chronic hepatitis C virus (HCV) infection who could be cured with a shorter duration of direct-acting antiviral (DAA) treatment. However, modeling therapy duration has yet to be evaluated in recently infected individuals. The aim of this study was to retrospectively examine whether modeling can predict outcomes of six-week sofosbuvir (SOF) and weight-based ribavirin (R) therapy in individuals with recent HCV infection. METHODS: Modeling was used to estimate viral host parameters and to predict time to cure for 12 adults with recent HCV infection (<12 months of infection) who received six weeks of treatment with SOF + R. RESULTS: Modeling results yielded a 100% negative predictive value for SOF + R treatment response in nine participants and suggested that a median of 13 [interquartile range: 8-16] weeks of therapy would be required for these patients to achieve cure. Modeling predicted cure after 5 weeks of therapy in the only modeled participant who achieved a sustained virological response. However, cure was also predicted for two participants who relapsed following treatment. CONCLUSIONS: The modeling results confirm that longer than 6 weeks of SOF + R is needed to reach cure in individuals with recent HCV infection. Prospective real-time modeling under current potent DAA regimens is needed to validate the potential of response-guided therapy in the management of recent HCV infection.
Asunto(s)
Antivirales/uso terapéutico , Duración de la Terapia , Hepatitis C/tratamiento farmacológico , Modelos Teóricos , Adulto , Anciano , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , ARN Viral/sangre , Estudios Retrospectivos , Ribavirina/uso terapéutico , Sofosbuvir/uso terapéutico , Respuesta Virológica Sostenida , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
We recently showed in a proof-of-concept study that real-time modeling-based response-guided therapy can shorten hepatitis C virus treatment duration with sofosbuvir-velpatasvir, elbasvir-grazoprevir, and sofosbuvir-ledipasvir without compromising efficacy, confirming our retrospective modeling reports in >200 patients. However, retrospective modeling of pibrentasvir-glecaprevir (P/G) treatment has yet to be evaluated. In the current study, modeling hepatitis C virus kinetics in 44 cirrhotic and noncirrhotic patients predicts that P/G treatment might have been reduced to 4, 6, and 7 weeks in 16%, 34%, and 14% of patients, respectively. These results support the further evaluation of a modeling-based response-guided therapy approach using P/G.
