Revisiting HBV resistance to entecavir with a phenotypic approach.

Revisiting HBV resistance to entecavir with a phenotypic approach. Antiviral Res. 2020 Jul 28;:104869 Authors: Marlet J, Lier C, Roch E, Maugey M, Moreau A, Combe B, Lefeuvre S, d'Alteroche L, Barbereau D, Causse X, Bastides F, Bachelier MN, Brand D, Gaudy-Graffin C 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 with...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research