Persistence of HIV-1 transmitted drug resistance mutations

Hannah Castro*, Deenan Pillay, Patricia Cane, David Asboe, Valentina Cambiano, Andrew Phillips, David T. Dunn, Celia Aitken, Anton Pozniak, Daniel Webster, David Dolling, Esther Fearnhill, Kholoud Porter, David Chadwick, Duncan Churchill, Duncan Clark, Simon Collins, Valerie Delpech, Anna Maria Geretti, David GoldbergAntony Hale, Stéphane Hué, Steve Kaye, Paul Kellam, Linda Lazarus, Andrew Leigh-Brown, Nicola Mackie, Chloe Orkin, Philip Rice, Caroline Sabin, Erasmus Smit, Kate Templeton, Peter Tilston, William Tong, Ian Williams, Hongyi Zhang, Mark Zuckerman, Jane Greatorex, Adrian Wildfire, Siobhan O'Shea, Jane Mullen, Tamyo Mbisa, Alison Cox, Richard Tandy, Tony Hale, Tracy Fawcett, Mark Hopkins, Lynn Ashton, Ana Garcia-Diaz, Jill Shepherd, Matthias L. Schmid, Brendan Payne, Phillip Hay, Phillip Rice, Mary Paynter, David Bibby, Stuart Kirk, Alasdair MacLean, Rory Gunson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)

Abstract

There are few data on the persistence of individual human immunodeficiency virus type 1 (HIV-1) transmitted drug resistance (TDR) mutations in the absence of selective drug pressure. We studied 313 patients in whom TDR mutations were detected at their first resistance test and who had a subsequent test performed while ART-naive. The rate at which mutations became undetectable was estimated using exponential regression accounting for interval censoring. Most thymidine analogue mutations (TAMs) and T215 revertants (but not T215F/Y) were found to be highly stable, with NNRTI and PI mutations being relatively less persistent. Our estimates are important for informing HIV transmission models.

Original languageEnglish
Pages (from-to)1459-1463
Number of pages5
JournalJournal of Infectious Diseases
Volume208
Issue number9
DOIs
Publication statusPublished - 1 Nov 2013

Bibliographical note

Funding Information:
Financial support. This work was supported by the UK Medical Research Council (grant G0900274) and the European Community’s 7th framework programme (FP7/2007–2013) under the Collaborative HIV and Anti-HIV Drug Resistance Network (CHAIN; project 223131).

Funding Information:
Acknowledgments. We thank the UK Collaborative HIV Cohort Study and the UK Register of HIV Seroconverters for providing demographic and clinical information for this study. UK HIV Drug Resistance Database Steering Committee: Celia Aitken, Gartnavel General Hospital, Glasgow; David Asboe, Anton Pozniak, Chelsea & Westminster Hospital, London; Daniel Webster, Royal Free NHS Trust, London; Patricia Cane, Health Protection Agency, Porton Down; Hannah Castro, David Dunn, David Dolling, Esther Fearnhill, Kholoud Porter, MRC Clinical Trials Unit, London; David Chadwick, South Tees Hospitals NHS Trust, Middlesbrough; Duncan Churchill, Brighton and Sussex University Hospitals NHS Trust; Duncan Clark, St Bartholomew’s and The London NHS Trust; Simon Collins, HIV i-Base, London; Valerie Delpech, Health Protection Agency, Centre for Infections, London; Anna Maria Geretti, University of Liverpool; David Goldberg, Health Protection Scotland, Glasgow; Antony Hale, Leeds Teaching Hospitals NHS Trust; Stéphane Hué, University College London; Steve Kaye, Imperial College London; Paul Kellam, Wellcome Trust Sanger Institute and UCL Medical School; Linda Lazarus, Expert Advisory Group on AIDS Secretariat, Health Protection Agency, London; Andrew Leigh-Brown, University of Edinburgh; Nicola Mackie, Imperial NHS Trust; Chloe Orkin, St. Bartholomew’s Hospital, London; Philip Rice, St George’s Healthcare Trust, London; Deenan Pillay, Andrew Phillips, Caroline Sabin, University College London Medical School; Erasmus Smit, Health Protection Agency, Birmingham Heartlands Hospital; Kate Templeton, Royal Infirmary of Edinburgh; Peter Tilston, Manchester Royal Infirmary; William Tong, Guy’s and St. Thomas’ NHS Foundation Trust, London; Ian Williams, Mortimer Market Centre, London; Hongyi Zhang, Addenbrooke’s Hospital, Cambridge; Mark Zuckerman, King’s College Hospital, London. Centres contributing data to UK HIV Drug Resistance Database: Clinical Microbiology and Public Health Laboratory, Addenbrooke’s Hospital, Cambridge ( Jane Greatorex); HIV/GUM Research Laboratory, Chelsea and Westminster Hospital, London (Adrian Wildfire); Guy’s and St. Thomas’ NHS Foundation Trust, London (Siobhan O’Shea, Jane Mullen); HPA – Public Health Laboratory, Birmingham Heartlands Hospital, Birmingham (Erasmus Smit); HPA 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 (Tony Hale, Tracy Fawcett); Specialist Virology Centre, Liverpool (Mark Hopkins, Lynn Ashton); Department of Clinical Virology, Manchester Royal Infirmary, Manchester (Peter Tilston); Department of Virology, Royal Free Hospital, London (Daniel Webster, Ana Garcia-Diaz); Edinburgh Specialist Virology Centre, Royal Infirmary of Edinburgh ( Jill Shepherd); Department of Infection and Tropical Medicine, Royal Victoria Infirmary, Newcastle (Matthias L Schmid, Brendan Payne); South Tees Hospitals NHS Trust, Middlesbrough (David Chadwick); St George’s Hospital, London (Phillip Hay, Phillip Rice, Mary Paynter); Department of Virology, St Bartholomew’s and The London NHS Trust (Duncan Clark, David Bibby); Molecular Diagnostic Unit, Imperial College, London (Steve Kaye); University College London Hospitals (Stuart Kirk); West of Scotland Specialist Virology Lab Gartnavel, Glasgow (Alasdair MacLean, Celia Aitken, Rory Gunson).

Keywords

  • HIV-1
  • mutations
  • persistence
  • resistance
  • transmitted

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