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SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity

Author

Listed:
  • Michele B. Daly

    (Centers for Disease Control and Prevention)

  • Chuong Dinh

    (Centers for Disease Control and Prevention)

  • Angela Holder

    (Centers for Disease Control and Prevention)

  • Donna Rudolph

    (Centers for Disease Control and Prevention)

  • Susan Ruone

    (Centers for Disease Control and Prevention)

  • Alison Swaims-Kohlmeier

    (Centers for Disease Control and Prevention
    Emory University School of Medicine)

  • George Khalil

    (Centers for Disease Control and Prevention
    Centers for Disease Control and Prevention)

  • Sunita Sharma

    (Centers for Disease Control and Prevention)

  • James Mitchell

    (Centers for Disease Control and Prevention)

  • Jillian Condrey

    (Centers for Disease Control and Prevention)

  • Daniel Kim

    (Centers for Disease Control and Prevention)

  • Yi Pan

    (Centers for Disease Control and Prevention)

  • Kelly Curtis

    (Centers for Disease Control and Prevention)

  • Peter Williams

    (Janssen Research & Development)

  • William Spreen

    (ViiV Healthcare)

  • Walid Heneine

    (Centers for Disease Control and Prevention)

  • J. Gerardo García-Lerma

    (Centers for Disease Control and Prevention)

Abstract

Studies in SIV-infected macaques show that the virus reservoir is particularly refractory to conventional suppressive antiretroviral therapy (ART). We posit that optimized ART regimens designed to have robust penetration in tissue reservoirs and long-lasting antiviral activity may be advantageous for HIV or SIV remission. Here we treat macaques infected with RT-SHIV with oral emtricitabine/tenofovir alafenamide and long-acting cabotegravir/rilpivirine without (n = 4) or with (n = 4) the immune activator vesatolimod after the initial onset of viremia. We document full suppression in all animals during treatment (4-12 months) and no virus rebound after treatment discontinuation (1.5-2 years of follow up) despite CD8 + T cell depletion. We show efficient multidrug penetration in virus reservoirs and persisting rilpivirine in plasma for 2 years after the last dose. Our results document a type of virus remission that is achieved through early treatment initiation and provision of ultra long-lasting antiviral activity that persists after treatment cessation.

Suggested Citation

  • Michele B. Daly & Chuong Dinh & Angela Holder & Donna Rudolph & Susan Ruone & Alison Swaims-Kohlmeier & George Khalil & Sunita Sharma & James Mitchell & Jillian Condrey & Daniel Kim & Yi Pan & Kelly C, 2024. "SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54783-0
    DOI: 10.1038/s41467-024-54783-0
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    References listed on IDEAS

    as
    1. Erica N. Borducchi & Jinyan Liu & Joseph P. Nkolola & Anthony M. Cadena & Wen-Han Yu & Stephanie Fischinger & Thomas Broge & Peter Abbink & Noe B. Mercado & Abishek Chandrashekar & David Jetton & Laur, 2018. "Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys," Nature, Nature, vol. 563(7731), pages 360-364, November.
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