Your browser doesn't support javascript.
loading
Frequency matters: comparison of drug resistance mutation detection by Sanger and next-generation sequencing in HIV-1.
Balakrishna, Suraj; Loosli, Tom; Zaheri, Maryam; Frischknecht, Paul; Huber, Michael; Kusejko, Katharina; Yerly, Sabine; Leuzinger, Karoline; Perreau, Matthieu; Ramette, Alban; Wymant, Chris; Fraser, Christophe; Kellam, Paul; Gall, Astrid; Hirsch, Hans H; Stoeckle, Marcel; Rauch, Andri; Cavassini, Matthias; Bernasconi, Enos; Notter, Julia; Calmy, Alexandra; Günthard, Huldrych F; Metzner, Karin J; Kouyos, Roger D.
Afiliación
  • Balakrishna S; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Loosli T; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Zaheri M; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Frischknecht P; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Huber M; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Kusejko K; Swiss National Center for Retroviruses, University of Zurich, Zurich, Switzerland.
  • Yerly S; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Leuzinger K; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Perreau M; Swiss National Center for Retroviruses, University of Zurich, Zurich, Switzerland.
  • Ramette A; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Wymant C; Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
  • Fraser C; Laboratory of Virology, University Hospital Geneva, University of Geneva, Geneva, Switzerland.
  • Kellam P; Clinical Virology Division, Laboratory Medicine, University Hospital Basel, Basel, Switzerland.
  • Gall A; Division of Immunology and Allergy, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland.
  • Hirsch HH; Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
  • Stoeckle M; Nuffield Department of Medicine, Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
  • Rauch A; Nuffield Department of Medicine, Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
  • Cavassini M; Nuffield Department of Medicine, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Bernasconi E; Department of Infectious Diseases, Faculty of Medicine, Imperial College London, London, UK.
  • Notter J; Excellence in Life Sciences (EMBO), Heidelberg, Germany.
  • Calmy A; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Günthard HF; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland.
  • Metzner KJ; Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Kouyos RD; Division of Infectious Diseases, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
J Antimicrob Chemother ; 78(3): 656-664, 2023 03 02.
Article en En | MEDLINE | ID: mdl-36738248
BACKGROUND: Next-generation sequencing (NGS) is gradually replacing Sanger sequencing (SS) as the primary method for HIV genotypic resistance testing. However, there are limited systematic data on comparability of these methods in a clinical setting for the presence of low-abundance drug resistance mutations (DRMs) and their dependency on the variant-calling thresholds. METHODS: To compare the HIV-DRMs detected by SS and NGS, we included participants enrolled in the Swiss HIV Cohort Study (SHCS) with SS and NGS sequences available with sample collection dates ≤7 days apart. We tested for the presence of HIV-DRMs and compared the agreement between SS and NGS at different variant-calling thresholds. RESULTS: We included 594 pairs of SS and NGS from 527 SHCS participants. Males accounted for 80.5% of the participants, 76.3% were ART naive at sample collection and 78.1% of the sequences were subtype B. Overall, we observed a good agreement (Cohen's kappa >0.80) for HIV-DRMs for variant-calling thresholds ≥5%. We observed an increase in low-abundance HIV-DRMs detected at lower thresholds [28/417 (6.7%) at 10%-25% to 293/812 (36.1%) at 1%-2% threshold]. However, such low-abundance HIV-DRMs were overrepresented in ART-naive participants and were in most cases not detected in previously sampled sequences suggesting high sequencing error for thresholds <3%. CONCLUSIONS: We found high concordance between SS and NGS but also a substantial number of low-abundance HIV-DRMs detected only by NGS at lower variant-calling thresholds. Our findings suggest that a substantial fraction of the low-abundance HIV-DRMs detected at thresholds <3% may represent sequencing errors and hence should not be overinterpreted in clinical practice.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Infecciones por VIH / VIH-1 / Seropositividad para VIH / Fármacos Anti-VIH Tipo de estudio: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Idioma: En Revista: J Antimicrob Chemother Año: 2023 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Infecciones por VIH / VIH-1 / Seropositividad para VIH / Fármacos Anti-VIH Tipo de estudio: Diagnostic_studies / Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Idioma: En Revista: J Antimicrob Chemother Año: 2023 Tipo del documento: Article