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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Frequency and patterns of protease gene resistance mutations in HIV-infected patients treated with lopinavir/ritonavir as their first protease inhibitor
Journal of Antimicrobial Chemotherapy, Volume 67, No. 4, Article dkr569, Year 2012
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Description
Background: Selection of protease mutations on antiretroviral therapy (ART) including a ritonavir-boosted protease inhibitor (PI) has been reported infrequently. Scarce data exist from long-term cohorts on resistance incidence or mutational patterns emerging to different PIs. Methods: We studied UK patients receiving lopinavir/ritonavir as their first PI, either while naive to ART or having previously received non-PI-based ART. Virological failure was defined as viral load ≥400 copies/mL after previous suppression <400 copies/mL, or failure to achieve <400 copies/mL during the first 6 months. pol sequences whilst failing lopinavir or within 30 days after stopping were analysed. Major and minor mutations (IAS-USA 2008-after exclusion of polymorphisms) were considered. Predicted susceptibility was determined using the Stanford HIVdb algorithm. Results: Three thousand and fifty-six patients were followed for a median (IQR) of 14 (6-30) months, of whom 811 (27%) experienced virological failure. Of these, resistance test results were available on 291 (36%). One or more protease mutations were detected in 32 (11%) patients; the most frequent were I54V (n = 12), M46I (n = 11), V82A (n = 7) and L76V (n = 3). No association with viral subtype was evident. Many patients retained virus predicted to be susceptible to lopinavir (14, 44%), tipranavir (26, 81%) and darunavir (27, 84%). Conclusions: This study reflects the experience of patients in routine care. Selection of protease gene mutations by lopinavir/ritonavir occurred at a much higher rate than in clinical trials. The mutations observed showed only partial overlap with those previously identified by structural chemistry models, serial cell culture passage and genotype-phenotype analyses. There remained a low degree of predicted cross-resistance to other widely used PIs. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Authors & Co-Authors
Harrison, Linda J.
United Kingdom, London
Medical Research Council
Asboe, David
United Kingdom, London
Chelsea and Westminster Hospital
Williams, Ian G.
United Kingdom, London
University College London
Kirk, Stuart
United Kingdom, London
University College London Hospitals Nhs Foundation Trust
Gilson, Richard John Cary
United Kingdom, London
University College London
Bansi-Matharu, Loveleen K.
United Kingdom, London
University College London
United Kingdom, London
Ucl Medical School
Morris, Lynn G.
United Kingdom, London
Medical Research Council
United Kingdom, London
Ucl Medical School
Dunn, David T.
United Kingdom, London
Medical Research Council
Anderson, Jane
United Kingdom, London
Homerton University Hospital Nhs Foundation Trust
Pozniak, Anton Louis
United Kingdom, London
Chelsea and Westminster Hospital
Cane, Patricia A.
United Kingdom, London
Public Health England
Chadwick, David Robert
United Kingdom, Middlesbrough
South Tees Hospitals Nhs Foundation Trust
Churchill, Duncan R.
United Kingdom, Worthing
University Hospitals Sussex Nhs Foundation Trust
Clark, Duncan A.
United Kingdom, London
St Bartholomew's Hospital
Collins, Simon
United Kingdom, London
Hiv I-base
Delpech, Valerie C.
United Kingdom, London
Public Health England
Lazarus, Linda
United Kingdom, London
Public Health England
Crofts, Jonathan P.
United Kingdom, London
Medical Research Council
Dolling, David I.
United Kingdom, London
Medical Research Council
Fearnhill, Esther
United Kingdom, London
Medical Research Council
Castro, Hannah
United Kingdom, London
Medical Research Council
Porter, Kholoud
United Kingdom, London
Medical Research Council
Geretti, Anna María
United Kingdom, London
Royal Free London Nhs Foundation Trust
Goldberg, David J.
United Kingdom, Glasgow
Health Protection Scotland
Gompels, Mark M.
United Kingdom, Bristol
Southmead Hospital Bristol
United Kingdom, Bristol
North Bristol Nhs Trust
Hale, Antony D.
United Kingdom, Leeds
Leeds Teaching Hospitals Nhs Trust
Kaye, Steve
United Kingdom, London
Imperial College London
Kellam, P.
United Kingdom, Hinxton
Wellcome Sanger Institute
Leigh Brown, Andrew J.
United Kingdom, Edinburgh
The University of Edinburgh
MacKie, Nicola E.
United Kingdom, London
St Mary's Hospital
Orkin, Chloë M.
United Kingdom, London
St Bartholomew's Hospital
United Kingdom, London
Barts Health Nhs Trust
Phillips, Andrew N.
United Kingdom, London
Ucl Medical School
Sabin, Caroline Anne
United Kingdom, London
Ucl Medical School
Smit, Erasmus J.
United Kingdom, London
Public Health England
Templeton, Kate E.
United Kingdom, Edinburgh
Royal Infirmary of Edinburgh
Tilston, Peter
United Kingdom, Manchester
Manchester Royal Infirmary
Zhang, Hongyi
United Kingdom, Cambridge
Addenbrooke's Hospital
Ushiro-Lumb, Inês
United Kingdom, London
St Bartholomew's Hospital
Bibby, David F.
United Kingdom, London
St Bartholomew's Hospital
Mbisa, Tamyo
United Kingdom, London
Public Health England
Shepherd, Jill A.
United Kingdom, Edinburgh
Royal Infirmary of Edinburgh
Gunson, Rory N.
United Kingdom, Glasgow
West of Scotland Specialist Virology Centre
Aitken, Celia
United Kingdom, Glasgow
West of Scotland Specialist Virology Centre
Bennett, Diane E.
United Kingdom, Leeds
Leeds Teaching Hospitals Nhs Trust
Hopkins, Mark J.
Unknown Affiliation
Payne, Brendan Alexander Ingelby
United Kingdom, Newcastle
Newcastle University
Booth, Clare L.
United Kingdom, London
The Royal Free Hospital
Garcia-Diaz, Ana M.
United Kingdom, London
The Royal Free Hospital
Ainsworth, Jonathan G.
United Kingdom, London
North Middlesex University Hospital Nhs Trust
Babiker, Abdel G.A.G.
Unknown Affiliation
Fisher, Martin J.
United Kingdom, Worthing
University Hospitals Sussex Nhs Foundation Trust
Gazzard, Brian George L.
United Kingdom, London
Chelsea and Westminster Hospital
Hill, Teresa
United Kingdom, London
Ucl Medical School
Johnson, Margaret A.
United Kingdom, London
Ucl Medical School
Leen, Clifford L.S.
United Kingdom, Edinburgh
Nhs Lothian
Nelson, Mark Richard
United Kingdom, London
Chelsea and Westminster Hospital
Palfreeman, Adrian J.
United Kingdom, Leicester
University of Leicester
Post, Frank A.
United Kingdom, London
King's College Hospital Nhs Foundation Trust
Sachikonye, Memory
Unknown Affiliation
Schwenk, Achim
United Kingdom, London
North Middlesex University Hospital Nhs Trust
Walsh, John Christopher
United Kingdom, London
St Mary's Hospital
Huntington, Susie E.
United Kingdom, London
Ucl Medical School
Glabay, Adam J.
United Kingdom, London
Medical Research Council
Garrett, Nigel J.
United Kingdom, London
Barts Health Nhs Trust
Lynch, Janet
United Kingdom, London
Barts Health Nhs Trust
Hand, James
United Kingdom, London
Barts Health Nhs Trust
de Souza, Carl B.S.S.
United Kingdom, London
Barts Health Nhs Trust
Perry, Nicky
United Kingdom, Worthing
University Hospitals Sussex Nhs Foundation Trust
Tilbury, Stuart
United Kingdom, Worthing
University Hospitals Sussex Nhs Foundation Trust
Waxman, Matthew
United Kingdom, London
Chelsea and Westminster Hospital
Mandalia, Sundhiya
United Kingdom, London
Chelsea and Westminster Hospital
Munshi, Sajid
United Kingdom, London
Homerton University Hospital Nhs Foundation Trust
Korat, Hardik
United Kingdom, London
King's College Hospital Nhs Foundation Trust
Taylor, Christopher B.
United Kingdom, London
King's College Hospital Nhs Foundation Trust
Gleisner, Zachary
United Kingdom, London
King's College Hospital Nhs Foundation Trust
Ibrahim, Fowzia A.
United Kingdom, London
King's College Hospital Nhs Foundation Trust
Campbell, Lucy J.
United Kingdom, London
King's College Hospital Nhs Foundation Trust
Brima, Nataliya
United Kingdom, London
University College London
Wood, Christopher W.
United Kingdom, London
North Middlesex University Hospital Nhs Trust
Miller, Sheila
United Kingdom, London
North Middlesex University Hospital Nhs Trust
Youle, Mike S.
United Kingdom, London
Ucl Medical School
Lampe, Fiona C.
United Kingdom, London
Ucl Medical School
Smith, Colette Joanne
United Kingdom, London
Ucl Medical School
Grabowska, Helen
United Kingdom, London
Ucl Medical School
Chaloner, Clinton
United Kingdom, London
Ucl Medical School
Puradiredja, Dewi Ismajani
United Kingdom, London
Ucl Medical School
Weber, Jonathan N.
United Kingdom, London
St Mary's Hospital
Ramzan, Farhan
United Kingdom, London
St Mary's Hospital
Winston, Alan
United Kingdom, London
St Mary's Hospital
Carder, Mark
United Kingdom, London
St Mary's Hospital
Wilson, Alan C.
United Kingdom, Edinburgh
Nhs Lothian
Allan, Sue
United Kingdom, Bristol
North Bristol Nhs Trust
Statistics
Citations: 23
Authors: 92
Affiliations: 35
Identifiers
Doi:
10.1093/jac/dkr569
ISSN:
14602091
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Study Design
Cohort Study