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Interaction of immunosuppressants with HCV antivirals daclatasvir and asunaprevir: combined effects with mycophenolic acid

AIM: To investigate the specific effects of immunosuppressants on the antiviral action of daclatasvir and asunaprevir. METHODS: The antiviral activity of daclatasvir (DCV) and asunaprevir (ASV) combined with immunosuppressants was tested using two in vitro models for hepatitis C virus (HCV) infectio...

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Detalles Bibliográficos
Autores principales: de Ruiter, Petra E, Gadjradj, Yashna, de Knegt, Robert J, Metselaar, Herold J, Ijzermans, Jan NM, van der Laan, Luc JW
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134272/
https://www.ncbi.nlm.nih.gov/pubmed/30211024
http://dx.doi.org/10.5500/wjt.v8.i5.156
Descripción
Sumario:AIM: To investigate the specific effects of immunosuppressants on the antiviral action of daclatasvir and asunaprevir. METHODS: The antiviral activity of daclatasvir (DCV) and asunaprevir (ASV) combined with immunosuppressants was tested using two in vitro models for hepatitis C virus (HCV) infection. RESULTS: Tacrolimus, rapamycin and cyclosporine did not negatively affect the antiviral action of DCV or ASV. Mycophenolic acid (MPA) showed additive antiviral effects combined with these direct acting antivirals (DAAs). MPA induces interferon-stimulated genes (ISGs) and is a potent GTP synthesis inhibitor. DCV or ASV did not induce ISGs expression nor affected ISG induction by MPA. Rather, the combined antiviral effect of MPA with DCV and ASV was partly mediated via inhibition of GTP synthesis. CONCLUSION: Immunosuppressants do not negatively affect the antiviral activity of DAAs. MPA has additive effect on the antiviral action of DCV and ASV. This combined benefit needs to be confirmed in prospective clinical trials.