Novel hepatitis B virus reverse transcriptase mutations in patients with sustained viremia despite long-term tenofovir treatment

Autor: Anni Winckelmann, Ulrik Fahnøe, Priyanka Shukla Bajpai, Magnus Illum Dalegaard, Andreas Lundh, Lene Ryom, Jens Bukh, Nina Weis
Rok vydání: 2022
Předmět:
Zdroj: University of Southern Denmark
Winckelmann, A, Fahnoe, U, Bajpai, P, Dalegaard, M I, Lundh, A, Ryom, L, Bukh, J & Weis, N 2021, ' Novel Hepatitis B Virus Reverse Transcriptase Mutations in Patients With Sustained Viremia Despite Long-Term Tenofovir Treatment ', Hepatology, vol. 74, no. Suppl. 1, pp. 488A-489A . < https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.32188 >
Winckelmann, A, Fahnøe, U, Bajpai, P S, Dalegaard, M I, Lundh, A, Ryom, L, Bukh, J & Weis, N 2022, ' Novel hepatitis B virus reverse transcriptase mutations in patients with sustained viremia despite long-term tenofovir treatment ', Journal of Clinical Virology, vol. 150-151, 105159 . https://doi.org/10.1016/j.jcv.2022.105159
ISSN: 1873-5967
DOI: 10.1002/hep.32188
Popis: Background: Chronic hepatitis B virus (HBV) treatment consists of nucleos(t)ide analogues to suppress viral replication. The HBV inhibitor tenofovir has a high barrier to resistance, however, evidence of virus-escape is emerging. This study investigates HBV evolution in patients undergoing tenofovir treatment with the primary aim to assess the emergence of putative resistance mutations. Methods: HBV DNA was extracted from blood samples of two patients with HBeAg-positive chronic HBV infection and persistent viremia despite tenofovir treatment, and subsequently amplified by PCR before full-length HBV genomes were assembled by deep sequencing. The mutation linkage within the viral population was evaluated by clonal analysis of amplicons. Results: Sequence analysis of HBV, derived from 11 samples collected 2010-2020 from one patient, identified 12 non-synonymous single-nucleotide polymorphisms (SNPs) emerging during a tenofovir treatment interruption from 2014 to 2017. Two of the SNPs were in the reverse transcriptase (RT; H35Q and D263E). The two RT mutations were linked and persisted despite restarting tenofovir treatment in 2017. For the second patient, we analyzed HBV derived from six samples collected 2014-2020 following 10 years of tenofovir treatment, and identified five non-synonymous SNPs, that confer resistance towards entecavir and/or lamivudine. Two RT mutations (H35N and P237T) emerged during subsequent 5-year entecavir treatment. H35N was maintained during final tenofovir treatment. Conclusions: Our findings indicate that changes at the conserved residue 35 (H35N/Q) in the HBV RT may be associated with tenofovir resistance. These variants have not previously been described, and further studies are warranted to assess resistance in vitro and in vivo.
Databáze: OpenAIRE
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