Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation

the UK HIV Drug Resistance Database and the UK Collaborative HIV Cohort

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1 Citation (Scopus)

Abstract

Objectives: The aim of the study was to investigate whether lamivudine (3TC) or emtricitabine (FTC) use following detection of M184V/I is associated with better virological outcomes. Methods: We identified people with viruses harbouring the M184V/I mutation in UK multicentre data sets who had treatment change/initiation within 1 year. We analysed outcomes of viral suppression (< 200 HIV-1 RNA copies/mL) and appearance of new major drug resistance mutations (DRMs) using Cox and Poisson models, with stratification by new drug regimen (excluding 3TC/FTC) and Bayesian implementation, and estimated the effect of 3TC/FTC adjusted for individual and viral characteristics. Results: We included 2597 people with the M184V/I resistance mutation, of whom 665 (25.6%) were on 3TC and 458 (17.6%) on FTC. We found a negative adjusted association between 3TC/FTC use and viral suppression [hazard ratio (HR) 0.84; 95% credibility interval (CrI) 0.71–0.98]. On subgroup analysis of individual drugs, there was no evidence of an association with viral suppression for 3TC (n = 184; HR 0.94; 95% CrI 0.73–1.15) or FTC (n = 454; HR 0.99; 95% CrI 0.80–1.19) amongst those on tenofovir-containing regimens, but we estimated a reduced rate of viral suppression for people on 3TC amongst those without tenofovir use (n = 481; HR 0.71; 95% CrI 0.54–0.90). We found no association between 3TC/FTC and detection of any new DRM (overall HR 0.92; 95% CrI 0.64–1.18), but found inconclusive evidence of a lower incidence rate of new DRMs (overall incidence rate ratio 0.69; 95% CrI 0.34–1.11). Conclusions: We did not find evidence that 3TC or FTC use is associated with an increase in viral suppression, but it may reduce the appearance of additional DRMs in people with M184V/I. 3TC was associated with reduced viral suppression amongst people on regimens without tenofovir.

Original languageEnglish
Pages (from-to)309-321
Number of pages13
JournalHIV Medicine
Volume21
Issue number5
DOIs
Publication statusPublished - 1 May 2020

Bibliographical note

Funding Information:
Financial disclosure : This work is currently supported by the UK Medical Research Council (Award Number 164587). 1

Funding Information:
Steering committee: Jonathan Ainsworth, Sris Allan, Jane Anderson, Ade Apoola, David Chadwick, Duncan Churchill, Valerie Delpech, David Dunn, Ian Fairley, Ashini Fox, Richard Gilson, Mark Gompels, Phillip Hay, Rajesh Hembrom, Teresa Hill, Margaret Johnson, Sophie Jose, Stephen Kegg, Clifford Leen, Dushyant Mital, Mark Nelson, Hajra Okhai, Chloe Orkin, Adrian Palfreeman, Andrew Phillips, Deenan Pillay, Ashley Price, Frank Post, Jillian Pritchard, Caroline Sabin, Achim Schwenk, Anjum Tariq, Roy Trevelion, Andy Ustianowski, John Walsh. Central co‐ordination : University College London (David Dunn, Teresa Hill, Hajra Okhai, Andrew Phillips, Caroline Sabin); Medical Research Council Clinical Trials Unit at UCL (MRC CTU at UCL), London (Nadine van Looy, Keith Fairbrother). Participating centres: Barts Health NHS Trust, London (Chloe Orkin, Janet Lynch, James Hand); Brighton and Sussex University Hospitals NHS Trust, Brighton (Duncan Churchill, Stuart Tilbury, Elaney Youssef, Duncan Churchill); Chelsea and Westminster Hospital NHS Foundation Trust, London (Mark Nelson, Richard Daly, David Asboe, Sundhiya Mandalia); Homerton University Hospital NHS Trust, London (Jane Anderson, Sajid Munshi); King’s College Hospital NHS Foundation Trust, London (Frank Post, Ade Adefisan, Chris Taylor, Zachary Gleisner, Fowzia Ibrahim, Lucy Campbell); South Tees Hospitals NHS Foundation Trust, Middlesbrough (David Chadwick, Kirsty Baillie); Mortimer Market Centre, University College London, London (Richard Gilson, Ian Williams); North Middlesex University Hospital NHS Trust, London (Jonathan Ainsworth, Achim Schwenk, Sheila Miller, Chris Wood); Royal Free NHS Foundation Trust/University College London, London (Margaret Johnson, Mike Youle, Fiona Lampe, Colette Smith, Rob Tsintas, Clinton Chaloner, Caroline Sabin, Andrew Phillips, Teresa Hill, Hajra Okhai); Imperial College Healthcare NHS Trust, London (John Walsh, Nicky Mackie, Alan Winston, Jonathan Weber, Farhan Ramzan, Mark Carder); The Lothian University Hospitals NHS Trust, Edinburgh (Clifford Leen, Andrew Kerr, David Wilks, Sheila Morris); North Bristol NHS Trust, Bristol (Mark Gompels, Sue Allan); University Hospitals of Leicester NHS Trust, Leicester (Adrian Palfreeman, Adam Lewszuk); Woolwich, Lewisham and Greenwich NHS Trust, London (Stephen Kegg, Victoria Ogunbiyi, Sue Mitchell), St. George’s Healthcare NHS Trust, London (Phillip Hay, Christopher Hunt, Olanike Okolo, Benjamin Watts); York Teaching Hospital NHS Foundation Trust, York (Ian Fairley, Sarah Russell‐Sharpe, Olatunde Fagbayimu); University Hospitals Coventry and Warwickshire NHS Trust, Coventry (Sris Allan, Debra Brain); The Royal Wolverhampton Hospitals NHS Trust, Wolverhampton (Anjum Tariq, Liz Radford, Sarah Milgate); Chertsey, Ashford and St. Peter’s Hospitals NHS Foundation Trust (Jillian Pritchard, Shirley Cumming, Claire Atkinson); Milton Keynes Hospital NHS Foundation Trust, Milton Keynes (Dushyant Mital, Annie Rose, Jeanette Smith); The Pennine Acute Hospitals NHS Trust (Andy Ustianowski, Cynthia Murphy, Ilise Gunder); Nottingham University Hospitals NHS Trust, Nottingham (Ashini Fox, Howard Gees, Gemma Squires, Laura Anderson), Kent Community Health NHS Foundation Trust (Rajesh Hembrom, Serena Mansfield, Lee Tomlinson, Christine LeHegerat, Roberta Box, Tom Hatton, Doreen Herbert), The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle (Ashley Price, Ian McVittie, Victoria Murtha, Laura Shewan); Derby Teaching Hospitals NHS Foundation Trust, Derby (Ade Apoola, Zak Connan, Luke Gregory, Kathleen Holding, Victoria Chester, Trusha Mistry, Catherine Gatford); Public Health England, London (Valerie Delpech); i‐Base (Roy Trevelion).

Funding Information:
Financial disclosure: This work is currently supported by the UK Medical Research Council (Award Number 164587).

Funding Information:
Steering committee: David Asboe, Anton Pozniak (Chelsea & Westminster Hospital, London); Patricia Cane (Public Health England, Porton Down); David Chadwick (South Tees Hospitals NHS Trust, Middlesbrough); Duncan Churchill (Brighton and Sussex University Hospitals NHS Trust, Brighton); Duncan Clark (Barts Health NHS Trust, London); Simon Collins (HIV i‐Base, London); Valerie Delpech (National Infection Service, Public Health England); Samuel Douthwaite (Guy’s and St. Thomas’ NHS Foundation Trust, London); David Dunn, Esther Fearnhill, Kholoud Porter, Anna Tostevin, Oliver Stirrup (Institute for Global Health, UCL, London); Christophe Fraser (University of Oxford,Oxford); Anna Maria Geretti (Institute of Infection and Global Health, University of Liverpool, Liverpool); Rory Gunson (Gartnavel General Hospital, Glasgow); Antony Hale (Leeds Teaching Hospitals NHS Trust, Leeds); Stéphane Hué (London School of Hygiene and Tropical Medicine, London); Linda Lazarus (Expert Advisory Group on AIDS Secretariat, Public Health England); Andrew Leigh‐Brown (University of Edinburgh, Edinburgh); Tamyo Mbisa (National Infection Service, Public Health England); Nicola Mackie (Imperial NHS Trust, London); Chloe Orkin (Barts Health NHS Trust, London); Eleni Nastouli, Deenan Pillay, Andrew Phillips, Caroline Sabin (University College London, London); Erasmus Smit (Public Health England, Birmingham Heartlands Hospital, Birmingham); Kate Templeton (Royal Infirmary of Edinburgh, Edinburgh); Peter Tilston (Manchester Royal Infirmary, Manchester); Erik Volz (Imperial College London, London); Ian Williams (Mortimer Market Centre, London); Hongyi Zhang (Addenbrooke’s Hospital, Cambridge). Coordinating centre: Institute for Global Health, UCL, London (David Dunn, Keith Fairbrother, Esther Fearnhill, Kholoud Porter, Anna Tostevin, Oliver Stirrup). Centres contributing data: Clinical Microbiology and Public Health Laboratory, Addenbrooke’s Hospital, Cambridge (Justine Dawkins); Guy’s and St Thomas’ NHS Foundation Trust, London (Siobhan O’Shea, Jane Mullen); PHE – Public Health Laboratory, Birmingham Heartlands Hospital, Birmingham (Erasmus Smit); Antiviral Unit, National Infection Service, Public Health England, London (Tamyo Mbisa); Imperial College Health NHS Trust, London (Alison Cox); King’s College Hospital, London (Richard Tandy); Medical Microbiology Laboratory, Leeds Teaching Hospitals NHS Trust, Leeds (Tracy Fawcett); Specialist Virology Centre, Liverpool (Mark Hopkins); Department of Clinical Virology, Manchester Royal Infirmary, Manchester (Peter Tilston); Department of Virology, Royal Free Hospital, London (Clare Booth, Ana Garcia‐Diaz); Edinburgh Specialist Virology Centre, Royal Infirmary of Edinburgh, Edinburgh (Lynne Renwick); Department of Infection & Tropical Medicine, Royal Victoria Infirmary, Newcastle (Matthias L. Schmid, Brendan Payne); South Tees Hospitals NHS Trust, Middlesbrough (David Chadwick); Department of Virology, Barts Health NHS Trust, London (Jonathan Hubb); Molecular Diagnostic Unit, Imperial College, London (Simon Dustan); University College London Hospitals, London (Stuart Kirk); West of Scotland Specialist Virology Laboratory, Gartnavel, Glasgow (Rory Gunson, Amanda Bradley‐Stewart).

Publisher Copyright:
© 2019 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association

Keywords

  • HIV
  • M184I
  • M184V
  • emtricitabine
  • lamivudine

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