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A majority of HIV persistence during antiretroviral therapy is due to infected cell proliferation

Author

Listed:
  • Daniel B. Reeves

    (Fred Hutchinson Cancer Research Center)

  • Elizabeth R. Duke

    (Fred Hutchinson Cancer Research Center
    University of Washington)

  • Thor A. Wagner

    (University of Washington
    Seattle Children’s Research Institute)

  • Sarah E. Palmer

    (The Westmead Institute for Medical Research, University of Sydney)

  • Adam M. Spivak

    (University of Utah)

  • Joshua T. Schiffer

    (Fred Hutchinson Cancer Research Center
    University of Washington
    Fred Hutchinson Cancer Research Center)

Abstract

Antiretroviral therapy (ART) suppresses viral replication in people living with HIV. Yet, infected cells persist for decades on ART and viremia returns if ART is stopped. Persistence has been attributed to viral replication in an ART sanctuary and long-lived and/or proliferating latently infected cells. Using ecological methods and existing data, we infer that >99% of infected cells are members of clonal populations after one year of ART. We reconcile our results with observations from the first months of ART, demonstrating mathematically how a fossil record of historic HIV replication permits observed viral evolution even while most new infected cells arise from proliferation. Together, our results imply cellular proliferation generates a majority of infected cells during ART. Therefore, reducing proliferation could decrease the size of the HIV reservoir and help achieve a functional cure.

Suggested Citation

  • Daniel B. Reeves & Elizabeth R. Duke & Thor A. Wagner & Sarah E. Palmer & Adam M. Spivak & Joshua T. Schiffer, 2018. "A majority of HIV persistence during antiretroviral therapy is due to infected cell proliferation," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06843-5
    DOI: 10.1038/s41467-018-06843-5
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    Cited by:

    1. Daniel B. Reeves & Christian Gaebler & Thiago Y. Oliveira & Michael J. Peluso & Joshua T. Schiffer & Lillian B. Cohn & Steven G. Deeks & Michel C. Nussenzweig, 2023. "Impact of misclassified defective proviruses on HIV reservoir measurements," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Daniel B. Reeves & Charline Bacchus-Souffan & Mark Fitch & Mohamed Abdel-Mohsen & Rebecca Hoh & Haelee Ahn & Mars Stone & Frederick Hecht & Jeffrey Martin & Steven G. Deeks & Marc K. Hellerstein & Jos, 2023. "Estimating the contribution of CD4 T cell subset proliferation and differentiation to HIV persistence," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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