Evidence of tenofovir resistance in chronic hepatitis B virus (HBV) infection: An observational case series of South African adults.
Africa
HBV
HIV
Nucleos(t)ide analogue
RAMs
Resistance
TDF
Tenofovir
Therapy
Viraemia
Journal
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
ISSN: 1873-5967
Titre abrégé: J Clin Virol
Pays: Netherlands
ID NLM: 9815671
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
23
06
2020
accepted:
07
07
2020
pubmed:
15
7
2020
medline:
21
8
2021
entrez:
15
7
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 32663786
pii: S1386-6532(20)30290-0
doi: 10.1016/j.jcv.2020.104548
pmc: PMC7408481
pii:
doi:
Substances chimiques
Antiviral Agents
0
DNA, Viral
0
Tenofovir
99YXE507IL
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104548Subventions
Organisme : Wellcome Trust
ID : 110110Z/15/Z
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest We have no conflicts of interest to declare.
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