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Heritability of the HIV-1 reservoir size and decay under long-term suppressive ART

Author

Listed:
  • Chenjie Wan

    (University Hospital Zurich
    ETH Zurich)

  • Nadine Bachmann

    (University Hospital Zurich
    University of Zurich)

  • Venelin Mitov

    (ETH Zurich
    Swiss Institute of Bioinformatics)

  • François Blanquart

    (Collège de France)

  • Susana Posada Céspedes

    (Swiss Institute of Bioinformatics
    Department of Biosystems Science and Engineering, ETH Zurich)

  • Teja Turk

    (University Hospital Zurich
    University of Zurich)

  • Kathrin Neumann

    (University Hospital Zurich
    University of Zurich)

  • Niko Beerenwinkel

    (Department of Biosystems Science and Engineering, ETH Zurich)

  • Jasmina Bogojeska

    (IBM Research - Zurich)

  • Jacques Fellay

    (EPFL
    Lausanne University Hospital and University of Lausanne)

  • Volker Roth

    (University of Basel)

  • Jürg Böni

    (University of Zurich)

  • Matthieu Perreau

    (University of Lausanne)

  • Thomas Klimkait

    (University of Basel)

  • Sabine Yerly

    (Geneva University Hospital)

  • Manuel Battegay

    (University of Basel)

  • Laura Walti

    (University of Bern)

  • Alexandra Calmy

    (University of Geneva)

  • Pietro Vernazza

    (Cantonal Hospital of St. Gallen)

  • Enos Bernasconi

    (Regional Hospital)

  • Matthias Cavassini

    (University of Lausanne)

  • Karin J. Metzner

    (University Hospital Zurich
    University of Zurich)

  • Huldrych F. Günthard

    (University Hospital Zurich
    University of Zurich)

  • Roger D. Kouyos

    (University Hospital Zurich
    University of Zurich)

Abstract

The HIV-1 reservoir is the major hurdle to curing HIV-1. However, the impact of the viral genome on the HIV-1 reservoir, i.e. its heritability, remains unknown. We investigate the heritability of the HIV-1 reservoir size and its long-term decay by analyzing the distribution of those traits on viral phylogenies from both partial-pol and viral near full-length genome sequences. We use a unique nationwide cohort of 610 well-characterized HIV-1 subtype-B infected individuals on suppressive ART for a median of 5.4 years. We find that a moderate but significant fraction of the HIV-1 reservoir size 1.5 years after the initiation of ART is explained by genetic factors. At the same time, we find more tentative evidence for the heritability of the long-term HIV-1 reservoir decay. Our findings indicate that viral genetic factors contribute to the HIV-1 reservoir size and hence the infecting HIV-1 strain may affect individual patients’ hurdle towards a cure.

Suggested Citation

  • Chenjie Wan & Nadine Bachmann & Venelin Mitov & François Blanquart & Susana Posada Céspedes & Teja Turk & Kathrin Neumann & Niko Beerenwinkel & Jasmina Bogojeska & Jacques Fellay & Volker Roth & Jürg , 2020. "Heritability of the HIV-1 reservoir size and decay under long-term suppressive ART," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19198-7
    DOI: 10.1038/s41467-020-19198-7
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