Evidence of tenofovir resistance in chronic hepatitis B virus (HBV) infection: An observational case series of South African adults

Mokaya, J. et al. (2020) Evidence of tenofovir resistance in chronic hepatitis B virus (HBV) infection: An observational case series of South African adults. Journal of Clinical Virology, 129, 104548. (doi: 10.1016/j.jcv.2020.104548) (PMID:32663786) (PMCID:PMC7408481)

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Abstract

Introduction: Tenofovir disoproxil fumarate (TDF) is widely recommended for treatment of chronic hepatitis B virus (HBV) infection because it is safe, affordable and has a high genetic barrier to resistance. TDF resistance associated mutations (RAMs) have been reported, but data are limited, particularly for Africa. We set out to identify potential RAMs in individuals with detectable HBV viraemia on TDF treatment. Methods: We recruited adults with chronic HBV infection from Cape Town, South Africa, identifying individuals with a TDF resistance phenotype, defined as persistent HBV vireamia despite >12 months of TDF treatment. We sequenced HBV DNA using MiSeq Illumina with whole genome target enrichment, and sought potential TDF RAMs, based on a pre-defined list of polymorphisms. Results: Among 66 individuals with chronic HBV (genotypes A and D), three met our clinical definition for TDF resistance, of whom two were coinfected with HIV. In one participant, the consensus HBV sequence contained nine polymorphisms that have been described in association with TDF resistance. Significant treatment non-adherence in this individual was unlikely, as HIV RNA was suppressed. TDF RAMs were also present in HBV sequences from the other two participants, but other factors including treatment non-adherence may also have had a role in failure of HBV DNA suppression in these cases. Discussion: Our findings add to the evidence that RAMs in HBV reverse transcriptase may underpin a TDF resistant phenotype. This is the first time these RAMs have been reported from Africa in association with clinical evidence of TDF resistance.

Item Type:Articles
Additional Information:This work was supported by the Leverhulme Mandela Rhodes Scholarship to JM, Wellcome Trust (grant number 110110Z/15/Z to PCM), the Medical Research Council UK to EB, the Oxford NIHR Biomedical Research Centre to EB.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Vattipally, Dr Sreenu and Singer, Dr Joshua
Authors: Mokaya, J., Maponga, T. G., McNaughton, A. L., Van Schalkwyk, M., Hugo, S., Singer, J. B., Sreenu, V. B., Bonsall, D., de Cesare, M., Andersson, M., Gabriel, S., Taljaard, J., Barnes, E., Preiser, W., Van Rensburg, C., and Matthews, P. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Clinical Virology
Publisher:Elsevier
ISSN:1386-6532
ISSN (Online):1873-5967
Published Online:08 July 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Journal of Clinical Virology 129:104548
Publisher Policy:Reproduced under a Creative Commons license

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