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Prevention of SIVmac251 reservoir seeding in rhesus monkeys by early antiretroviral therapy

Author

Listed:
  • James B. Whitney

    (Harvard Medical School
    Ragon Institute of MGH, MIT, and Harvard)

  • So-Yon Lim

    (Harvard Medical School)

  • Christa E. Osuna

    (Harvard Medical School)

  • Jessica L. Kublin

    (Harvard Medical School)

  • Elsa Chen

    (Harvard Medical School)

  • Gyeol Yoon

    (Harvard Medical School)

  • Po-Ting Liu

    (Harvard Medical School)

  • Peter Abbink

    (Harvard Medical School)

  • Erica N. Borducci

    (Harvard Medical School)

  • Alison Hill

    (Harvard University)

  • Mark G. Lewis

    (Bioqual)

  • Romas Geleziunas

    (Gilead Sciences)

  • Merlin L. Robb

    (Henry Jackson Foundation)

  • Nelson L. Michael

    (Walter Reed Army Institute of Research)

  • Dan H. Barouch

    (Harvard Medical School
    Ragon Institute of MGH, MIT, and Harvard)

Abstract

The precise time when the viral reservoir is seeded during acute HIV-1 infection remains unclear. We previously demonstrated that the viral reservoir was seeded by day 3 following SIVmac251 infection in rhesus monkeys. Here we report the impact of initiating ART on day 0 (6 h), 1, 2, or 3 following intrarectal SIVmac251 infection in 20 rhesus monkeys (N = 5/group). After 6 months of daily suppressive ART, antiretroviral drugs were discontinued, and viral rebound was monitored. 0% (0 of 5), 20% (1 of 5), 60% (3 of 5), and 100% (5 of 5) of animals that initiated ART on days 0 (6 h), 1, 2, or 3, respectively, showed viral rebound following ART discontinuation and correlated with integrated viral DNA in lymph node CD4+ T cells. These data demonstrate that the viral reservoir is seeded within the first few days of infection and that early ART initiation limits the viral reservoir.

Suggested Citation

  • James B. Whitney & So-Yon Lim & Christa E. Osuna & Jessica L. Kublin & Elsa Chen & Gyeol Yoon & Po-Ting Liu & Peter Abbink & Erica N. Borducci & Alison Hill & Mark G. Lewis & Romas Geleziunas & Merlin, 2018. "Prevention of SIVmac251 reservoir seeding in rhesus monkeys by early antiretroviral therapy," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07881-9
    DOI: 10.1038/s41467-018-07881-9
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    Cited by:

    1. Christiaan H van Dorp & Jessica M Conway & Dan H Barouch & James B Whitney & Alan S Perelson, 2020. "Models of SIV rebound after treatment interruption that involve multiple reactivation events," PLOS Computational Biology, Public Library of Science, vol. 16(10), pages 1-25, October.
    2. Xiaolei Wang & Eunice Vincent & Summer Siddiqui & Katherine Turnbull & Hong Lu & Robert Blair & Xueling Wu & Meagan Watkins & Widade Ziani & Jiasheng Shao & Lara A. Doyle-Meyers & Kasi E. Russell-Lodr, 2022. "Early treatment regimens achieve sustained virologic remission in infant macaques infected with SIV at birth," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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