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Ultra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection

Author

Listed:
  • Isabella C. Young

    (University of North Carolina at Chapel Hill)

  • Ivana Massud

    (Centers for Disease Control and Prevention)

  • Mackenzie L. Cottrell

    (University of North Carolina at Chapel Hill)

  • Roopali Shrivastava

    (North Carolina State University and The University of North Carolina at Chapel Hill)

  • Panita Maturavongsadit

    (North Carolina State University and The University of North Carolina at Chapel Hill)

  • Alka Prasher

    (North Carolina State University and The University of North Carolina at Chapel Hill)

  • Andres Wong-Sam

    (Centers for Disease Control and Prevention)

  • Chuong Dinh

    (Centers for Disease Control and Prevention)

  • Tiancheng Edwards

    (Centers for Disease Control and Prevention)

  • Victoria Mrotz

    (National Center for Emerging and Zoonotic Infection Diseases, Centers for Disease Control and Prevention)

  • James Mitchell

    (Centers for Disease Control and Prevention)

  • Josilene Nascimento Seixas

    (Centers for Disease Control and Prevention)

  • Aryani Pallerla

    (University of North Carolina at Chapel Hill)

  • Allison Thorson

    (North Carolina State University and The University of North Carolina at Chapel Hill)

  • Amanda Schauer

    (University of North Carolina at Chapel Hill)

  • Craig Sykes

    (University of North Carolina at Chapel Hill)

  • Gabriela Cruz

    (University of North Carolina School of Medicine)

  • Stephanie A. Montgomery

    (University of North Carolina School of Medicine)

  • Angela D. M. Kashuba

    (University of North Carolina at Chapel Hill)

  • Walid Heneine

    (Centers for Disease Control and Prevention)

  • Charles W. Dobard

    (Centers for Disease Control and Prevention)

  • Martina Kovarova

    (University of North Carolina at Chapel Hill)

  • J. Victor Garcia

    (University of North Carolina at Chapel Hill)

  • J. Gerardo Garcίa-Lerma

    (Centers for Disease Control and Prevention)

  • S. Rahima Benhabbour

    (University of North Carolina at Chapel Hill
    North Carolina State University and The University of North Carolina at Chapel Hill)

Abstract

Ultra-long-acting delivery platforms for HIV pre-exposure prophylaxis (PrEP) may increase adherence and maximize public health benefit. We report on an injectable, biodegradable, and removable in-situ forming implant (ISFI) that is administered subcutaneously and can release the integrase inhibitor cabotegravir (CAB) above protective benchmarks for more than 6 months. CAB ISFIs are well-tolerated in female mice and female macaques showing no signs of toxicity or chronic inflammation. In macaques, median plasma CAB concentrations exceed established PrEP protection benchmarks within 3 weeks and confer complete protection against repeated rectal SHIV challenges. Implant removal via a small incision in 2 macaques at week 12 results in a 7- to 48-fold decrease in plasma CAB levels within 72 hours. Modeling to translate CAB ISFI dosing suggests that a 3 mL injection would exceed protective benchmarks in humans for over 5 months post administration. Our results support the clinical advancement of CAB ISFIs for ultra-long-acting PrEP in humans.

Suggested Citation

  • Isabella C. Young & Ivana Massud & Mackenzie L. Cottrell & Roopali Shrivastava & Panita Maturavongsadit & Alka Prasher & Andres Wong-Sam & Chuong Dinh & Tiancheng Edwards & Victoria Mrotz & James Mitc, 2023. "Ultra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36330-5
    DOI: 10.1038/s41467-023-36330-5
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    References listed on IDEAS

    as
    1. Martina Kovarova & S. Rahima Benhabbour & Ivana Massud & Rae Ann Spagnuolo & Brianna Skinner & Caroline E. Baker & Craig Sykes & Katie R. Mollan & Angela D. M. Kashuba & J. Gerardo García-Lerma & Russ, 2018. "Ultra-long-acting removable drug delivery system for HIV treatment and prevention," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

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