Skip to Main content Skip to Navigation
Journal articles

Revisiting HBV resistance to entecavir with a phenotypic approach

Abstract : Treatment adaptation after hepatitis B virus (HBV) treatment failure relies on genotypic resistance testing. However, the results of such tests are not always consistent with treatment response. These discrepancies may be due to differences in resistance levels between isolates with the same genotypic resistance testing profiles. We explored this hypothesis by investigating six cases of entecavir treatment failure with an integrative strategy combining genotypic and phenotypic resistance testing, medical record review and therapeutic drug monitoring. Among isolates with genotypic reduced susceptibility to entecavir, one displayed a higher level of resistance to entecavir (mean fold change in entecavir IC50 of 1 508 ± 531 vs. 318 ± 53, p=0.008). This isolate harbored a substitution (rt250L) at a position reported to be associated with resistance (rt250V). Reversion to wild-type amino acid at this position partially restored susceptibility to entecavir, confirming that the rt250L mutation was responsible for the high level of resistance to entecavir. This is the first description of entecavir treatment failure associated with selection of the rt250L mutation without other entecavir resistance mutations. One isolate with genotypic resistance to entecavir, harboring the rt173L mutation, displayed a lower level of resistance than the other, harboring the rt202G mutation (mean fold change of 323 ± 124 vs. 6 036 ± 2 100, p=0.20). These results suggest that isolates harboring the rt250L mutations should be considered resistant to entecavir, whereas isolates harboring the rt173L mutations should be considered to display reduced susceptibility to entecavir. An integrative approach to antiviral drug resistance in HBV would provide a more accurate assessment of entecavir treatment failures and help to improve the accuracy of genotypic testing algorithms.
Complete list of metadatas

Cited literature [26 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02908432
Contributor : Julien Marlet <>
Submitted on : Wednesday, July 29, 2020 - 9:06:36 AM
Last modification on : Tuesday, August 4, 2020 - 8:11:32 AM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : 2021-01-28

Please log in to resquest access to the document

Identifiers

Collections

Citation

Julien Marlet, Clément Lier, Emmanuelle Roch, Morgan Maugey, Alain Moreau, et al.. Revisiting HBV resistance to entecavir with a phenotypic approach. Antiviral Research, Elsevier Masson, 2020, pp.104869. ⟨10.1016/j.antiviral.2020.104869⟩. ⟨inserm-02908432⟩

Share

Metrics

Record views

63