Impact of a decade of successful antiretroviral therapy initiated at HIV-1 seroconversion on blood and rectal reservoirs

Abstract

Persistent reservoirs remain the major obstacles to achieve an HIV-1 cure. Prolonged early antiretroviral therapy (ART) may reduce the extent of reservoirs and allow for virological control after ART discontinuation. We compared HIV-1 reservoirs in a cross-sectional study using PCR-based techniques in blood and tissue of early treated seroconverters, late treated patients, ART-naïve seroconverters and long-term non-progressors (LTNPs) who have spontaneous virological control without treatment. A decade of early ART reduced total and integrated HIV-1 DNA levels compared to later treatment initiation, but not reaching the low levels of LTNPs. Total HIV-1 DNA in rectal biopsies did not differ between cohorts. Importantly, lower viral transcription (unspliced RNA) and enhanced immune preservation (CD4/CD8) reminiscent of LTNPs were found in early compared to late treated patients. This suggests that early treatment is associated with some immuno-virological features of LTNPs that may improve the outcome of future interventions aimed at a functional cure.

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Author details

  1. Eva Malatinkova

    HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitair Ziekenhuis Gent, Ghent University, Ghent, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  2. Ward De Spiegelaere

    HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitair Ziekenhuis Gent, Ghent University, Ghent, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  3. Pawel Bonczkowski

    HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitair Ziekenhuis Gent, Ghent University, Ghent, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  4. Maja Kiselinova

    HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitair Ziekenhuis Gent, Ghent University, Ghent, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  5. Karen Vervisch

    HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitair Ziekenhuis Gent, Ghent University, Ghent, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  6. Wim Trypsteen

    HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitair Ziekenhuis Gent, Ghent University, Ghent, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  7. Margaret Johnson

    Division of Infection and Immunity, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Chris Verhofstede

    AIDS Reference Laboratory, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  9. Danny de Looze

    Department of Gastroenterology, Universitair Ziekenhuis Gent, Ghent University, Ghent, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  10. Charles Murray

    Department of Gastroenterology, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Sabine Kinloch-de Loes

    Division of Infection and Immunity, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Linos Vandekerckhove

    HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Universitair Ziekenhuis Gent, Ghent University, Ghent, Belgium
    For correspondence
    linos.vandekerckhove@ugent.be
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Human subjects: Patient written informed consent was obtained from all the study participants.The study was approved by the Ethical Committee of Ghent University Hospital (Reference number: B670201317826) and Royal Free Hospital (Reference number: 13/LO/0729).

Copyright

© 2015, Malatinkova 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. Eva Malatinkova
  2. Ward De Spiegelaere
  3. Pawel Bonczkowski
  4. Maja Kiselinova
  5. Karen Vervisch
  6. Wim Trypsteen
  7. Margaret Johnson
  8. Chris Verhofstede
  9. Danny de Looze
  10. Charles Murray
  11. Sabine Kinloch-de Loes
  12. Linos Vandekerckhove
(2015)
Impact of a decade of successful antiretroviral therapy initiated at HIV-1 seroconversion on blood and rectal reservoirs
eLife 4:e09115.
https://doi.org/10.7554/eLife.09115

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https://doi.org/10.7554/eLife.09115

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