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Daclatasvir plasma level and resistance selection in HIV patients with hepatitis C virus cirrhosis treated with daclatasvir, sofosbuvir, and ribavirin

Saverio G. Parisi, Arianna Loregian, Samantha Andreis, Giulio Nannetti Orcid Logo, Silvia Cavinato, Monica Basso, Renzo Scaggiante, Federico Dal Bello, Lorenzo Messa, Anna Maria Cattelan, Giorgio Palù

International Journal of Infectious Diseases, Volume: 49, Pages: 151 - 153

Swansea University Author: Giulio Nannetti Orcid Logo

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DOI (Published version): 10.1016/j.ijid.2016.06.020

Abstract

ObjectivesEffective treatment with direct-acting antiviral drugs against hepatitis C virus (HCV) is a medical need in cirrhotic HIV–HCV co-infected patients.MethodsThis study investigated the plasma levels of daclatasvir (DCV) and ribavirin (RBV) in HIV–HCV co-infected subjects treated with DCV, sof...

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Published in: International Journal of Infectious Diseases
ISSN: 1201-9712
Published: Elsevier BV 2016
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URI: https://cronfa.swan.ac.uk/Record/cronfa57646
Abstract: ObjectivesEffective treatment with direct-acting antiviral drugs against hepatitis C virus (HCV) is a medical need in cirrhotic HIV–HCV co-infected patients.MethodsThis study investigated the plasma levels of daclatasvir (DCV) and ribavirin (RBV) in HIV–HCV co-infected subjects treated with DCV, sofosbuvir, and RBV. Drug concentrations were quantified using validated high-performance liquid chromatography methods with ultraviolet detection. The HCV non-structural protein 5A and non-structural protein 5B coding regions were analyzed by population-based sequencing.ResultsDCV was dosed at week 4 and at week 8 of treatment, and RBV at week 8. One patient had the lowest DCV level, corresponding to 32.7% of the overall median value of the other patients at week 4 and about 40% at week 8. The Y93H variant was detected in this subject at weeks 8, 16, and 20 of treatment, but not before treatment or at day 2, and the patient experienced virological failure. Another subject with the Y93H variant at baseline and appropriate DCV levels had HCV RNA <12 IU/ml at week 12 and undetectable at week 16.ConclusionsSub-optimal DCV drug levels allow the selection of resistance-associated variants and fail to contribute to antiviral activity. No definite reason for the low DCV level was found. Quantifying the drug is suggested in difficult-to-treat patients.
Keywords: Daclatasvir; HIV–HCV patients; Therapeutic drug monitoring; Virological failure; Population-based sequencing; Mutation
College: Faculty of Medicine, Health and Life Sciences
Start Page: 151
End Page: 153

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