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Evidence of tenofovir resistance in chronic hepatitis B virus (HBV) infection: An observational case series of South African adults
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, particu...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408481/ https://www.ncbi.nlm.nih.gov/pubmed/32663786 http://dx.doi.org/10.1016/j.jcv.2020.104548 |
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author | Mokaya, Jolynne Maponga, Tongai G McNaughton, Anna L Van Schalkwyk, Marije Hugo, Susan Singer, Joshua B Sreenu, Vattipally B Bonsall, David de Cesare, Mariateresa Andersson, Monique Gabriel, Shiraaz Taljaard, Jantje Barnes, Eleanor Preiser, Wolfgang Van Rensburg, Christo Matthews, Philippa C |
author_facet | Mokaya, Jolynne Maponga, Tongai G McNaughton, Anna L Van Schalkwyk, Marije Hugo, Susan Singer, Joshua B Sreenu, Vattipally B Bonsall, David de Cesare, Mariateresa Andersson, Monique Gabriel, Shiraaz Taljaard, Jantje Barnes, Eleanor Preiser, Wolfgang Van Rensburg, Christo Matthews, Philippa C |
author_sort | Mokaya, Jolynne |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7408481 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-74084812020-08-12 Evidence of tenofovir resistance in chronic hepatitis B virus (HBV) infection: An observational case series of South African adults Mokaya, Jolynne Maponga, Tongai G McNaughton, Anna L Van Schalkwyk, Marije Hugo, Susan Singer, Joshua B Sreenu, Vattipally B Bonsall, David de Cesare, Mariateresa Andersson, Monique Gabriel, Shiraaz Taljaard, Jantje Barnes, Eleanor Preiser, Wolfgang Van Rensburg, Christo Matthews, Philippa C J Clin Virol Article 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. Elsevier Science 2020-08 /pmc/articles/PMC7408481/ /pubmed/32663786 http://dx.doi.org/10.1016/j.jcv.2020.104548 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mokaya, Jolynne Maponga, Tongai G McNaughton, Anna L Van Schalkwyk, Marije Hugo, Susan Singer, Joshua B Sreenu, Vattipally B Bonsall, David de Cesare, Mariateresa Andersson, Monique Gabriel, Shiraaz Taljaard, Jantje Barnes, Eleanor Preiser, Wolfgang Van Rensburg, Christo Matthews, Philippa C Evidence of tenofovir resistance in chronic hepatitis B virus (HBV) infection: An observational case series of South African adults |
title | Evidence of tenofovir resistance in chronic hepatitis B virus (HBV) infection: An observational case series of South African adults |
title_full | Evidence of tenofovir resistance in chronic hepatitis B virus (HBV) infection: An observational case series of South African adults |
title_fullStr | Evidence of tenofovir resistance in chronic hepatitis B virus (HBV) infection: An observational case series of South African adults |
title_full_unstemmed | Evidence of tenofovir resistance in chronic hepatitis B virus (HBV) infection: An observational case series of South African adults |
title_short | Evidence of tenofovir resistance in chronic hepatitis B virus (HBV) infection: An observational case series of South African adults |
title_sort | evidence of tenofovir resistance in chronic hepatitis b virus (hbv) infection: an observational case series of south african adults |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408481/ https://www.ncbi.nlm.nih.gov/pubmed/32663786 http://dx.doi.org/10.1016/j.jcv.2020.104548 |
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