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Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing

Cozzi-Lepri, Alessandro ; Noguera-Julian, Marc ; Di Giallonardo, Francesca ; Schuurman, Rob ; Däumer, Martin ; Aitken, Sue ; Ceccherini-Silberstein, Francesca ; D'Arminio Monforte, Antonella ; Geretti, Anna Maria ; Booth, Clare L. ; Kaiser, Rolf ; Michalik, Claudia ; Jansen, Klaus ; Masquelier, Bernard ; Bellecave, Pantxika ; Kouyos, Roger D. ; Castro, Erika ; Furrer, Hansjakob ; Schultze, Anna ; Günthard, Huldrych F. ; Brun-Vezinet, Francoise ; Paredes, Roger ; Metzner, Karin J. ; Paredes, Roger ; Metzner, Karin J. ; Cozzi-Lepri, Alessandro ; Schuurman, Rob ; Brun-Vezinet, Francoise ; Günthard, Huldrych ; Ceccherini-Silberstein, Francesca ; Kaiser, Rolf ; Geretti, Anna Maria ; Brockmeyer, Norbert ; Masquelier, Bernard ; Paredes, Roger ; Metzner, Karin J. ; Cozzi-Lepri, Alessandro ; Schuurman, Rob ; Brun-Vezinet, Francoise ; Günthard, Huldrych ; Ceccherini-Silberstein, Francesca ; Kaiser, Rolf ; Geretti, Anna Maria ; Brockmeyer, Norbert ; Masquelier, Bernard

In: Journal of Antimicrobial Chemotherapy, 2015, vol. 70, no. 3, p. 930-940

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    Titre
    • Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing
    Auteur
    • Cozzi-Lepri, Alessandro. University College London, London, UK
    • Noguera-Julian, Marc. Institut de Recerca de la SIDA IrsiCaixa i Unitat VIH, Universitat Autònoma de Barcelona, Universitat de Vic, Catalonia, Spain
    • Di Giallonardo, Francesca. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
    • Schuurman, Rob. Department of Virology, University Medical Centre, Utrecht, The Netherlands
    • Däumer, Martin. Institut für Immunologie und Genetik, Kaiserslautern, Germany
    • Aitken, Sue. Department of Virology, University Medical Centre, Utrecht, The Netherlands
    • Ceccherini-Silberstein, Francesca. Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy
    • D'Arminio Monforte, Antonella. Department of Health Sciences, Clinic of Infectious Diseases, ‘San Paolo' Hospital, University of Milan, Milan, Italy
    • Geretti, Anna Maria. Institute of Infection & Global Health, University of Liverpool, Liverpool, UK
    • Booth, Clare L.. Department of Virology, Royal Free London NHS Foundation Trust, London, UK
    • Kaiser, Rolf. Institute of Virology, University of Cologne, Cologne, Germany
    • Michalik, Claudia. Competence Network for HIV/AIDS, Bochum, Germany and Clinic for Dermatology, Venerology and Allergology of the Ruhr-Universität, Bochum, Germany
    • Jansen, Klaus. Competence Network for HIV/AIDS, Bochum, Germany and Clinic for Dermatology, Venerology and Allergology of the Ruhr-Universität, Bochum, Germany
    • Masquelier, Bernard. Laboratoire de Virologie, CHU de Bordeaux and MFP-UMR5234, Université Bordeaux 2, Bordeaux, France
    • Bellecave, Pantxika. Laboratoire de Virologie, CHU de Bordeaux and MFP-UMR5234, Université Bordeaux 2, Bordeaux, France
    • Kouyos, Roger D.. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
    • Castro, Erika. Addiction Medicine, Service of Community Psychiatry, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
    • Furrer, Hansjakob. Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland
    • Schultze, Anna. University College London, London, UK
    • Günthard, Huldrych F.. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
    • Brun-Vezinet, Francoise. Department of Virology, Bichat University Hospital, Paris, France
    • Paredes, Roger. Institut de Recerca de la SIDA IrsiCaixa i Unitat VIH, Universitat Autònoma de Barcelona, Universitat de Vic, Catalonia, Spain
    • Metzner, Karin J.. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
    • Paredes, Roger. University College London, London, Institut de Recerca de la SIDA IrsiCaixa i Unitat VIH, Universitat Autònoma de Barcelona, Catalonia, Division of Infectious Diseases and Hospital Epidemiology, Zurich, Department of Virology, Utrecht, Kaiserslautern, Department of Experimental Medicine and Surgery, Rome, Department of Health Sciences, Clinic of Infectious Diseases, Milan, Institute of Infection & Global Health, Liverpool, Department of Virology, London, Institute of Virology, Cologne, Competence Network for HIV/AIDS, Bochum, Germany and Clinic for Dermatology, Bochum, Clinical Trial Centre (ZKS), Cologne, Laboratoire de Virologie, CHU de Bordeaux and MFP-UMR5234, Bordeaux, Addiction Medicine, Service of Community Psychiatry, Lausanne, Department of Infectious Diseases, Bern, Department of Virology, UK, Spain, Switzerland, The Netherlands, Germany, Italy, Italy, UK, UK, Germany, Germany, Germany, France, Switzerland, Switzerland, France
    • Metzner, Karin J.. University College London, London, Institut de Recerca de la SIDA IrsiCaixa i Unitat VIH, Universitat Autònoma de Barcelona, Catalonia, Division of Infectious Diseases and Hospital Epidemiology, Zurich, Department of Virology, Utrecht, Kaiserslautern, Department of Experimental Medicine and Surgery, Rome, Department of Health Sciences, Clinic of Infectious Diseases, Milan, Institute of Infection & Global Health, Liverpool, Department of Virology, London, Institute of Virology, Cologne, Competence Network for HIV/AIDS, Bochum, Germany and Clinic for Dermatology, Bochum, Clinical Trial Centre (ZKS), Cologne, Laboratoire de Virologie, CHU de Bordeaux and MFP-UMR5234, Bordeaux, Addiction Medicine, Service of Community Psychiatry, Lausanne, Department of Infectious Diseases, Bern, Department of Virology, UK, Spain, Switzerland, The Netherlands, Germany, Italy, Italy, UK, UK, Germany, Germany, Germany, France, Switzerland, Switzerland, France
    • Cozzi-Lepri, Alessandro. University College London, London, Institut de Recerca de la SIDA IrsiCaixa i Unitat VIH, Universitat Autònoma de Barcelona, Catalonia, Division of Infectious Diseases and Hospital Epidemiology, Zurich, Department of Virology, Utrecht, Kaiserslautern, Department of Experimental Medicine and Surgery, Rome, Department of Health Sciences, Clinic of Infectious Diseases, Milan, Institute of Infection & Global Health, Liverpool, Department of Virology, London, Institute of Virology, Cologne, Competence Network for HIV/AIDS, Bochum, Germany and Clinic for Dermatology, Bochum, Clinical Trial Centre (ZKS), Cologne, Laboratoire de Virologie, CHU de Bordeaux and MFP-UMR5234, Bordeaux, Addiction Medicine, Service of Community Psychiatry, Lausanne, Department of Infectious Diseases, Bern, Department of Virology, UK, Spain, Switzerland, The Netherlands, Germany, Italy, Italy, UK, UK, Germany, Germany, Germany, France, Switzerland, Switzerland, France
    • Schuurman, Rob. University College London, London, Institut de Recerca de la SIDA IrsiCaixa i Unitat VIH, Universitat Autònoma de Barcelona, Catalonia, Division of Infectious Diseases and Hospital Epidemiology, Zurich, Department of Virology, Utrecht, Kaiserslautern, Department of Experimental Medicine and Surgery, Rome, Department of Health Sciences, Clinic of Infectious Diseases, Milan, Institute of Infection & Global Health, Liverpool, Department of Virology, London, Institute of Virology, Cologne, Competence Network for HIV/AIDS, Bochum, Germany and Clinic for Dermatology, Bochum, Clinical Trial Centre (ZKS), Cologne, Laboratoire de Virologie, CHU de Bordeaux and MFP-UMR5234, Bordeaux, Addiction Medicine, Service of Community Psychiatry, Lausanne, Department of Infectious Diseases, Bern, Department of Virology, UK, Spain, Switzerland, The Netherlands, Germany, Italy, Italy, UK, UK, Germany, Germany, Germany, France, Switzerland, Switzerland, France
    • Brun-Vezinet, Francoise. University College London, London, Institut de Recerca de la SIDA IrsiCaixa i Unitat VIH, Universitat Autònoma de Barcelona, Catalonia, Division of Infectious Diseases and Hospital Epidemiology, Zurich, Department of Virology, Utrecht, Kaiserslautern, Department of Experimental Medicine and Surgery, Rome, Department of Health Sciences, Clinic of Infectious Diseases, Milan, Institute of Infection & Global Health, Liverpool, Department of Virology, London, Institute of Virology, Cologne, Competence Network for HIV/AIDS, Bochum, Germany and Clinic for Dermatology, Bochum, Clinical Trial Centre (ZKS), Cologne, Laboratoire de Virologie, CHU de Bordeaux and MFP-UMR5234, Bordeaux, Addiction Medicine, Service of Community Psychiatry, Lausanne, Department of Infectious Diseases, Bern, Department of Virology, UK, Spain, Switzerland, The Netherlands, Germany, Italy, Italy, UK, UK, Germany, Germany, Germany, France, Switzerland, Switzerland, France
    • Günthard, Huldrych. University College London, London, Institut de Recerca de la SIDA IrsiCaixa i Unitat VIH, Universitat Autònoma de Barcelona, Catalonia, Division of Infectious Diseases and Hospital Epidemiology, Zurich, Department of Virology, Utrecht, Kaiserslautern, Department of Experimental Medicine and Surgery, Rome, Department of Health Sciences, Clinic of Infectious Diseases, Milan, Institute of Infection & Global Health, Liverpool, Department of Virology, London, Institute of Virology, Cologne, Competence Network for HIV/AIDS, Bochum, Germany and Clinic for Dermatology, Bochum, Clinical Trial Centre (ZKS), Cologne, Laboratoire de Virologie, CHU de Bordeaux and MFP-UMR5234, Bordeaux, Addiction Medicine, Service of Community Psychiatry, Lausanne, Department of Infectious Diseases, Bern, Department of Virology, UK, Spain, Switzerland, The Netherlands, Germany, Italy, Italy, UK, UK, Germany, Germany, Germany, France, Switzerland, Switzerland, France
    • Ceccherini-Silberstein, Francesca. University College London, London, Institut de Recerca de la SIDA IrsiCaixa i Unitat VIH, Universitat Autònoma de Barcelona, Catalonia, Division of Infectious Diseases and Hospital Epidemiology, Zurich, Department of Virology, Utrecht, Kaiserslautern, Department of Experimental Medicine and Surgery, Rome, Department of Health Sciences, Clinic of Infectious Diseases, Milan, Institute of Infection & Global Health, Liverpool, Department of Virology, London, Institute of Virology, Cologne, Competence Network for HIV/AIDS, Bochum, Germany and Clinic for Dermatology, Bochum, Clinical Trial Centre (ZKS), Cologne, Laboratoire de Virologie, CHU de Bordeaux and MFP-UMR5234, Bordeaux, Addiction Medicine, Service of Community Psychiatry, Lausanne, Department of Infectious Diseases, Bern, Department of Virology, UK, Spain, Switzerland, The Netherlands, Germany, Italy, Italy, UK, UK, Germany, Germany, Germany, France, Switzerland, Switzerland, France
    • Kaiser, Rolf. University College London, London, Institut de Recerca de la SIDA IrsiCaixa i Unitat VIH, Universitat Autònoma de Barcelona, Catalonia, Division of Infectious Diseases and Hospital Epidemiology, Zurich, Department of Virology, Utrecht, Kaiserslautern, Department of Experimental Medicine and Surgery, Rome, Department of Health Sciences, Clinic of Infectious Diseases, Milan, Institute of Infection & Global Health, Liverpool, Department of Virology, London, Institute of Virology, Cologne, Competence Network for HIV/AIDS, Bochum, Germany and Clinic for Dermatology, Bochum, Clinical Trial Centre (ZKS), Cologne, Laboratoire de Virologie, CHU de Bordeaux and MFP-UMR5234, Bordeaux, Addiction Medicine, Service of Community Psychiatry, Lausanne, Department of Infectious Diseases, Bern, Department of Virology, UK, Spain, Switzerland, The Netherlands, Germany, Italy, Italy, UK, UK, Germany, Germany, Germany, France, Switzerland, Switzerland, France
    • Geretti, Anna Maria. University College London, London, Institut de Recerca de la SIDA IrsiCaixa i Unitat VIH, Universitat Autònoma de Barcelona, Catalonia, Division of Infectious Diseases and Hospital Epidemiology, Zurich, Department of Virology, Utrecht, Kaiserslautern, Department of Experimental Medicine and Surgery, Rome, Department of Health Sciences, Clinic of Infectious Diseases, Milan, Institute of Infection & Global Health, Liverpool, Department of Virology, London, Institute of Virology, Cologne, Competence Network for HIV/AIDS, Bochum, Germany and Clinic for Dermatology, Bochum, Clinical Trial Centre (ZKS), Cologne, Laboratoire de Virologie, CHU de Bordeaux and MFP-UMR5234, Bordeaux, Addiction Medicine, Service of Community Psychiatry, Lausanne, Department of Infectious Diseases, Bern, Department of Virology, UK, Spain, Switzerland, The Netherlands, Germany, Italy, Italy, UK, UK, Germany, Germany, Germany, France, Switzerland, Switzerland, France
    • Brockmeyer, Norbert. University College London, London, Institut de Recerca de la SIDA IrsiCaixa i Unitat VIH, Universitat Autònoma de Barcelona, Catalonia, Division of Infectious Diseases and Hospital Epidemiology, Zurich, Department of Virology, Utrecht, Kaiserslautern, Department of Experimental Medicine and Surgery, Rome, Department of Health Sciences, Clinic of Infectious Diseases, Milan, Institute of Infection & Global Health, Liverpool, Department of Virology, London, Institute of Virology, Cologne, Competence Network for HIV/AIDS, Bochum, Germany and Clinic for Dermatology, Bochum, Clinical Trial Centre (ZKS), Cologne, Laboratoire de Virologie, CHU de Bordeaux and MFP-UMR5234, Bordeaux, Addiction Medicine, Service of Community Psychiatry, Lausanne, Department of Infectious Diseases, Bern, Department of Virology, UK, Spain, Switzerland, The Netherlands, Germany, Italy, Italy, UK, UK, Germany, Germany, Germany, France, Switzerland, Switzerland, France
    • Masquelier, Bernard. University College London, London, Institut de Recerca de la SIDA IrsiCaixa i Unitat VIH, Universitat Autònoma de Barcelona, Catalonia, Division of Infectious Diseases and Hospital Epidemiology, Zurich, Department of Virology, Utrecht, Kaiserslautern, Department of Experimental Medicine and Surgery, Rome, Department of Health Sciences, Clinic of Infectious Diseases, Milan, Institute of Infection & Global Health, Liverpool, Department of Virology, London, Institute of Virology, Cologne, Competence Network for HIV/AIDS, Bochum, Germany and Clinic for Dermatology, Bochum, Clinical Trial Centre (ZKS), Cologne, Laboratoire de Virologie, CHU de Bordeaux and MFP-UMR5234, Bordeaux, Addiction Medicine, Service of Community Psychiatry, Lausanne, Department of Infectious Diseases, Bern, Department of Virology, UK, Spain, Switzerland, The Netherlands, Germany, Italy, Italy, UK, UK, Germany, Germany, Germany, France, Switzerland, Switzerland, France
    • Paredes, Roger
    • Metzner, Karin J.
    • Cozzi-Lepri, Alessandro
    • Schuurman, Rob
    • Brun-Vezinet, Francoise
    • Günthard, Huldrych
    • Ceccherini-Silberstein, Francesca
    • Kaiser, Rolf
    • Geretti, Anna Maria
    • Brockmeyer, Norbert
    • Masquelier, Bernard
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Journal of Antimicrobial Chemotherapy, 2015, vol. 70, no. 3, p. 930-940. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:299410
    Summary
    Objectives It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. Methods This Europe-wide case-control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. Results Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found. Conclusions Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART