1. Human Biology and Medicine
  2. Microbiology and Infectious Disease
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HIV-1 DNA predicts disease progression and post-treatment virological control

  1. James P Williams
  2. Jacob Hurst
  3. Wolfgang Stöhr
  4. Nicola Robinson
  5. Helen Brown
  6. Martin Fisher
  7. Sabine Kinloch
  8. David Cooper
  9. Mauro Schechter
  10. Giuseppe Tambussi
  11. Sarah Fidler
  12. Mary Carrington
  13. Abdel Babiker
  14. Jonathan Weber
  15. Kersten K Koelsch
  16. Anthony D Kelleher
  17. Rodney E Phillips
  18. John Frater  Is a corresponding author
  19. on behalf of the SPARTAC Trial Investigators
  1. University of Oxford, United Kingdom
  2. Institute of Clinical Trials and Methodology, University College London, United Kingdom
  3. Brighton and Sussex University Hospitals, United Kingdom
  4. University College London, United Kingdom
  5. St Vincent's Centre for Applied Medical Research, Australia
  6. Universidade Federal do Rio de Janeiro, Brazil
  7. Ospedale San Raffaele, Italy
  8. Wright Fleming Institute, Imperial College, United Kingdom
  9. Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, United States
Research Article
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Cite this article as: eLife 2014;3:e03821 doi: 10.7554/eLife.03821

Abstract

In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials.

Article and author information

Author details

  1. James P Williams

    University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Jacob Hurst

    University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Wolfgang Stöhr

    Institute of Clinical Trials and Methodology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Nicola Robinson

    University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Helen Brown

    University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Martin Fisher

    Brighton and Sussex University Hospitals, Brighton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Sabine Kinloch

    University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. David Cooper

    St Vincent's Centre for Applied Medical Research, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  9. Mauro Schechter

    Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  10. Giuseppe Tambussi

    Ospedale San Raffaele, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.
  11. Sarah Fidler

    Wright Fleming Institute, Imperial College, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Mary Carrington

    Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Abdel Babiker

    Institute of Clinical Trials and Methodology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  14. Jonathan Weber

    Wright Fleming Institute, Imperial College, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  15. Kersten K Koelsch

    St Vincent's Centre for Applied Medical Research, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  16. Anthony D Kelleher

    St Vincent's Centre for Applied Medical Research, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  17. Rodney E Phillips

    University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  18. John Frater

    University of Oxford, Oxford, United Kingdom
    For correspondence
    john.frater@ndm.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Human subjects: The SPARTAC trial was approved by the following authorities: Medicines and Healthcare products Regulatory Agency (UK), Ministry of Health (Brazil), Irish Medicines Board (Ireland), Medicines Control Council (South Africa), and The Uganda National Council for Science and Technology (Uganda). It was also approved by the following ethics committees in the participating countries: Central London Research Ethics Committee (UK), Hospital Universitário Clementino Fraga Filho Ethics in Research Committee (Brazil), Clinical Research and Ethics Committee of Hospital Clinic in the province of Barcelona, Spain, The Adelaide and Meath Hospital Research Ethics Committee (Ireland), University of Witwatersrand Human Research Ethics Committee, University of Kwazulu-Natal Research Ethics Committee and University of Cape Town Research Ethics Committee (South Africa), Uganda Virus Research Institute Science and ethics committee (Uganda), The Prince Charles Hospital Human Research Ethics Committee and St Vincent's Hospital Human Research Ethics Committee (Australia), and the National Institute for Infectious Diseases Lazzaro Spallanzani, Institute Hospital and the Medical Research Ethics Committee, and the ethical committee Of the Central Foundation of San Raffaele, MonteTabor (Italy). All participants signed a written informed consent.

Reviewing Editor

  1. Quarraisha Abdool Karim, University of KwaZulu Natal, South Africa

Publication history

  1. Received: June 28, 2014
  2. Accepted: September 4, 2014
  3. Accepted Manuscript published: September 12, 2014 (version 1)
  4. Version of Record published: October 16, 2014 (version 2)

Copyright

© 2014, Williams et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Further reading

Further reading

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