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. 2020 Nov 2;11(1):5542.
doi: 10.1038/s41467-020-19198-7.

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

Chenjie Wan  1   2 , Nadine Bachmann  1   3 , Venelin Mitov  4   5 , François Blanquart  6 , Susana Posada Céspedes  5   7 , Teja Turk  1   3 , Kathrin Neumann  1   3 , Niko Beerenwinkel  7 , Jasmina Bogojeska  8 , Jacques Fellay  9   10 , Volker Roth  11 , Jürg Böni  3 , Matthieu Perreau  12 , Thomas Klimkait  13 , Sabine Yerly  14 , Manuel Battegay  15 , Laura Walti  16 , Alexandra Calmy  17 , Pietro Vernazza  18 , Enos Bernasconi  19 , Matthias Cavassini  20 , Karin J Metzner  1   3 , Huldrych F Günthard  1   3 , Roger D Kouyos  21   22 ; Swiss HIV Cohort Study
Collaborators, Affiliations

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

Chenjie Wan et al. Nat Commun. .

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.

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Conflict of interest statement

M.C. has received research and travel grants for his institution from ViiV and Gilead. E.B. has received fees for his institution for participation to advisory board from MSD, Gilead Sciences, ViiV Healthcare, Abbvie and Janssen. M.B. has received research or educational grants by Abbvie AG, Gilead Sciences Switzerland Sàrl, Janssen-Cilag AG, MSD Merck Sharp & Dohme AG and ViiV Healthcare GmbH. T.K. has received honoraria from Gilead Sciences and Roche Diagnostics. L.W. has received honoraria for advisory boards and/or travel grants: MSD, Gilead Sciences. All remuneration went to her home institution and not to L.W. personally. R.D.K. has received grants from the Swiss National Science Foundation and personal fees from Gilead Sciences, outside the submitted work. H.F.G. has received unrestricted research grants from Gilead Sciences and Roche; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Merck, ViiV, Sandoz and Mepha. K.J.M. has received travel grants and honoraria from Gilead Sciences, Roche Diagnostics, GlaxoSmithKline, Merck Sharp & Dohme, Bristol-Myers Squibb, ViiV and Abbott; and the University of Zurich received research grants from Gilead Science, Roche, and Merck Sharp & Dohme for studies that Dr. Metzner serves as principal investigator, and advisory board honoraria from Gilead Sciences. All other authors have no potential conflict of interest.

Figures

Fig. 1
Fig. 1. Patient inclusion flowchart.
ART antiretroviral therapy, PBMC peripheral blood mononuclear cells.
Fig. 2
Fig. 2. Heritability estimates for HIV-1 reservoir size based on the phylogenies built from near full-length HIV-1 genome NGS sequences and partial pol Sanger sequences.
OU: Ornstein Uhlenbeck model. BM: Brownian motion model. ME: Mixed-effect model with corresponding phylogenetic distance threshold (substitutions per site). N: Number of patients included in the analysis. Patients with incomplete information of potential covariables were excluded. For BM and OU, all eligible patients from the tree were included while for mixed-effect model, only patients in the extracted transmission clusters were included. Black dots and black confidence intervals show the heritability estimates adjusted for covariables while blue rectangles and gray confidence intervals show the unadjusted estimates. 95% confidence intervals are shown in square brackets.
Fig. 3
Fig. 3. Heritability estimates for HIV-1 reservoir decay slope based on phylogenies built from near full-length HIV-1 genome NGS sequences and partial pol Sanger sequences.
OU: Ornstein Uhlenbeck model. BM: Brownian motion model. ME: Mixed-effect model with corresponding phylogenetic distance threshold (substitutions per site). N: Number of patients included in the analysis. Patients with incomplete information of potential covariables were excluded. For BM and OU, all eligible patients from the tree were included while for mixed-effect model, only patients in the extracted transmission clusters were included. Black dots and black confidence intervals show the heritability estimates adjusted for covariables while blue rectangles and gray confidence intervals show the unadjusted estimates. 95% confidence intervals are shown in square brackets.
See this image and copyright information in PMC

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