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

Chenjie Wan, Nadine Bachmann, Venelin Mitov, François Blanquart, Susana Posada Céspedes, Teja Turk, Kathrin Neumann, Niko Beerenwinkel, Jasmina Bogojeska, Jacques Fellay, Volker Roth, Jürg Böni, Matthieu Perreau, Thomas Klimkait, Sabine Yerly, Manuel Battegay, Laura Walti, Alexandra Calmy, Pietro Vernazza, Enos Bernasconi, Matthias Cavassini, Karin J. Metzner, Huldrych F. Günthard and Roger D. Kouyos ()
Additional contact information
Chenjie Wan: University Hospital Zurich
Nadine Bachmann: University Hospital Zurich
Venelin Mitov: ETH Zurich
François Blanquart: Collège de France
Susana Posada Céspedes: Swiss Institute of Bioinformatics
Teja Turk: University Hospital Zurich
Kathrin Neumann: University Hospital Zurich
Niko Beerenwinkel: Department of Biosystems Science and Engineering, ETH Zurich
Jasmina Bogojeska: IBM Research - Zurich
Jacques Fellay: EPFL
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
Huldrych F. Günthard: University Hospital Zurich
Roger D. Kouyos: University Hospital Zurich

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19198-7

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