Predictors of SIV recrudescence following antiretroviral treatment interruption

  1. Mykola Pinkevych
  2. Christine M Fennessey
  3. Deborah Cromer
  4. Carolyn Reid
  5. Charles M Trubey
  6. Jeffrey D Lifson
  7. Brandon F Keele  Is a corresponding author
  8. Miles P Davenport  Is a corresponding author
  1. University of New South Wales, Australia
  2. Frederick National Laboratory for Cancer Research, United States

Abstract

There is currently a need for proxy measures of the HIV rebound competent reservoir (RCR) that can predict viral rebound after combined antiretroviral treatment (cART) interruption. In this study, macaques infected with a barcoded SIVmac239 virus received cART beginning between 4- and 27-days post-infection, leading to the establishment of different levels of viral dissemination and persistence. Later treatment initiation led to higher SIV DNA levels maintained during treatment, which was significantly associated with an increased frequency of SIV reactivation and production of progeny capable of causing rebound viremia following treatment interruption. However, a 100-fold increase in SIV DNA in PBMCs was associated with only a 2-fold increase in the frequency of reactivation. These data suggest that the RCR can be established soon after infection, and that a large fraction of persistent viral DNA that accumulates after this time makes relatively little contribution to viral rebound.

Data availability

Source data files have been provided for Figures.

The following previously published data sets were used

Article and author information

Author details

  1. Mykola Pinkevych

    Infection Analytics Program, Kirby Institute for Infection and Immunity, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. Christine M Fennessey

    AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Deborah Cromer

    Infection Analytics Program, Kirby Institute for Infection and Immunity, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Carolyn Reid

    AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Charles M Trubey

    AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jeffrey D Lifson

    AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Brandon F Keele

    AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, United States
    For correspondence
    keelebf@mail.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
  8. Miles P Davenport

    Infection Analytics Program, Kirby Institute for Infection and Immunity, University of New South Wales, Sydney, Australia
    For correspondence
    M.Davenport@unsw.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4751-1831

Funding

National Institutes of Health (HHSN261200800001E)

  • Christine M Fennessey
  • Carolyn Reid
  • Charles M Trubey
  • Jeffrey D Lifson
  • Brandon F Keele

National Health and Medical Research Council (1052979)

  • Mykola Pinkevych
  • Deborah Cromer
  • Miles P Davenport

National Health and Medical Research Council (1149990)

  • Mykola Pinkevych
  • Deborah Cromer
  • Miles P Davenport

National Health and Medical Research Council (1080001)

  • Miles P Davenport

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Frank Kirchhoff, Ulm University Medical Center, Germany

Ethics

Animal experimentation: Animals were cared for in accordance with the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC) standards in an AAALAC-accredited facility and all procedures were performed according to protocols approved by the Institutional Animal Care and Use Committee of the National Cancer Institute (Assurance #A4149-01). Animal care was provided in accordance with the procedures outlined in the "Guide for Care and Use of Laboratory Animals". Reference numbers associated with the ethical approval are AVP047 and AVP058.

Version history

  1. Received: June 4, 2019
  2. Accepted: October 24, 2019
  3. Accepted Manuscript published: October 25, 2019 (version 1)
  4. Version of Record published: December 17, 2019 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Mykola Pinkevych
  2. Christine M Fennessey
  3. Deborah Cromer
  4. Carolyn Reid
  5. Charles M Trubey
  6. Jeffrey D Lifson
  7. Brandon F Keele
  8. Miles P Davenport
(2019)
Predictors of SIV recrudescence following antiretroviral treatment interruption
eLife 8:e49022.
https://doi.org/10.7554/eLife.49022

Share this article

https://doi.org/10.7554/eLife.49022

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