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Persistent HIV-1 replication maintains the tissue reservoir during therapy

Author

Listed:
  • Ramon Lorenzo-Redondo

    (Northwestern University Feinberg School of Medicine)

  • Helen R. Fryer

    (Institute for Emerging Infections, University of Oxford)

  • Trevor Bedford

    (Fred Hutchinson Cancer Research Center)

  • Eun-Young Kim

    (Northwestern University Feinberg School of Medicine)

  • John Archer

    (Centro de Investigação em Biodiversidade e Recursos Genéticos Universidade do Porto)

  • Sergei L. Kosakovsky Pond

    (University of California, San Diego
    † Present address: Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, Pennsylvania 19122-1801, USA.)

  • Yoon-Seok Chung

    (Center for Immunology and Pathology, Korea National Institutes of Health)

  • Sudhir Penugonda

    (Northwestern University Feinberg School of Medicine)

  • Jeffrey G. Chipman

    (University of Minnesota)

  • Courtney V. Fletcher

    (Antiviral Pharmacology Laboratory, University of Nebraska Medical Center, College of Pharmacy)

  • Timothy W. Schacker

    (University of Minnesota)

  • Michael H. Malim

    (King’s College London, Guy’s Hospital)

  • Andrew Rambaut

    (Centre for Immunology, Infection and Evolution, University of Edinburgh)

  • Ashley T. Haase

    (University of Minnesota)

  • Angela R. McLean

    (Institute for Emerging Infections, University of Oxford)

  • Steven M. Wolinsky

    (Northwestern University Feinberg School of Medicine)

Abstract

Lymphoid tissue is a key reservoir established by HIV-1 during acute infection. It is a site associated with viral production, storage of viral particles in immune complexes, and viral persistence. Although combinations of antiretroviral drugs usually suppress viral replication and reduce viral RNA to undetectable levels in blood, it is unclear whether treatment fully suppresses viral replication in lymphoid tissue reservoirs. Here we show that virus evolution and trafficking between tissue compartments continues in patients with undetectable levels of virus in their bloodstream. We present a spatial and dynamic model of persistent viral replication and spread that indicates why the development of drug resistance is not a foregone conclusion under conditions in which drug concentrations are insufficient to completely block virus replication. These data provide new insights into the evolutionary and infection dynamics of the virus population within the host, revealing that HIV-1 can continue to replicate and replenish the viral reservoir despite potent antiretroviral therapy.

Suggested Citation

  • Ramon Lorenzo-Redondo & Helen R. Fryer & Trevor Bedford & Eun-Young Kim & John Archer & Sergei L. Kosakovsky Pond & Yoon-Seok Chung & Sudhir Penugonda & Jeffrey G. Chipman & Courtney V. Fletcher & Tim, 2016. "Persistent HIV-1 replication maintains the tissue reservoir during therapy," Nature, Nature, vol. 530(7588), pages 51-56, February.
    • Handle: RePEc:nat:nature:v:530:y:2016:i:7588:d:10.1038_nature16933
    DOI: 10.1038/nature16933
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    Cited by:

    1. Caroline Dufour & Corentin Richard & Marion Pardons & Marta Massanella & Antoine Ackaoui & Ben Murrell & Bertrand Routy & Réjean Thomas & Jean-Pierre Routy & Rémi Fromentin & Nicolas Chomont, 2023. "Phenotypic characterization of single CD4+ T cells harboring genetically intact and inducible HIV genomes," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Omolara O. Baiyegunhi & Jaclyn Mann & Trevor Khaba & Thandeka Nkosi & Anele Mbatha & Funsho Ogunshola & Caroline Chasara & Nasreen Ismail & Thandekile Ngubane & Ismail Jajbhay & Johan Pansegrouw & Kri, 2022. "CD8 lymphocytes mitigate HIV-1 persistence in lymph node follicular helper T cells during hyperacute-treated infection," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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