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

Jolynne Mokaya; Tongai G Maponga; Anna L McNaughton; Marije Van Schalkwyk; Susan Hugo; Joshua B Singer; Vattipally B Sreenu; David Bonsall; Mariateresa de Cesare; Monique Andersson; Shiraaz Gabriel; Jantje Taljaard; Eleanor Barnes; Wolfgang Preiser; Christo Van Rensburg; Philippa C Matthews

doi:10.1016/j.jcv.2020.104548

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

Jolynne Mokaya, Tongai G Maponga, Anna L McNaughton, Marije Van Schalkwyk, Susan Hugo, Joshua B Singer, Vattipally B Sreenu, David Bonsall, Mariateresa de Cesare, Monique Andersson, Shiraaz Gabriel, Jantje Taljaard, Eleanor Barnes, Wolfgang Preiser, Christo Van Rensburg, Philippa C Matthews^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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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.

Original language	English
Pages (from-to)	104548
Number of pages	5
Journal	Journal of Clinical Virology
Volume	129
DOIs	https://doi.org/10.1016/j.jcv.2020.104548
Publication status	Published - 8 Jul 2020

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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., & Matthews, P. C. (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. https://doi.org/10.1016/j.jcv.2020.104548

@article{3f0de8d028dd43ed9491cce2eee9dcb8,

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

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.",

author = "Jolynne Mokaya and Maponga, {Tongai G} and McNaughton, {Anna L} and {Van Schalkwyk}, Marije and Susan Hugo and Singer, {Joshua B} and Sreenu, {Vattipally B} and David Bonsall and {de Cesare}, Mariateresa and Monique Andersson and Shiraaz Gabriel and Jantje Taljaard and Eleanor Barnes and Wolfgang Preiser and {Van Rensburg}, Christo and Matthews, {Philippa C}",

year = "2020",

month = jul,

day = "8",

doi = "10.1016/j.jcv.2020.104548",

language = "English",

volume = "129",

pages = "104548",

journal = "Journal of Clinical Virology",

issn = "1386-6532",

publisher = "Elsevier",

}

Mokaya, J, Maponga, TG, McNaughton, AL, Van Schalkwyk, M, Hugo, S, Singer, JB, Sreenu, VB, Bonsall, D, de Cesare, M, Andersson, M, Gabriel, S, Taljaard, J, Barnes, E, Preiser, W, Van Rensburg, C & Matthews, PC 2020, 'Evidence of tenofovir resistance in chronic hepatitis B virus (HBV) infection: An observational case series of South African adults', Journal of Clinical Virology, vol. 129, pp. 104548. https://doi.org/10.1016/j.jcv.2020.104548

TY - JOUR

T1 - Evidence of tenofovir resistance in chronic hepatitis B virus (HBV) infection

T2 - An observational case series of South African adults

AU - Mokaya, Jolynne

AU - Maponga, Tongai G

AU - McNaughton, Anna L

AU - Van Schalkwyk, Marije

AU - Hugo, Susan

AU - Singer, Joshua B

AU - Sreenu, Vattipally B

AU - Bonsall, David

AU - de Cesare, Mariateresa

AU - Andersson, Monique

AU - Gabriel, Shiraaz

AU - Taljaard, Jantje

AU - Barnes, Eleanor

AU - Preiser, Wolfgang

AU - Van Rensburg, Christo

AU - Matthews, Philippa C

PY - 2020/7/8

Y1 - 2020/7/8

N2 - 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.

AB - 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.

U2 - 10.1016/j.jcv.2020.104548

DO - 10.1016/j.jcv.2020.104548

M3 - Article (Academic Journal)

C2 - 32663786

SN - 1386-6532

VL - 129

SP - 104548

JO - Journal of Clinical Virology

JF - Journal of Clinical Virology

ER -

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

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