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Ultra-long-acting removable drug delivery system for HIV treatment and prevention

Author

Listed:
  • Martina Kovarova

    (Center for AIDS Research, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill)

  • S. Rahima Benhabbour

    (UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill)

  • Ivana Massud

    (National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention)

  • Rae Ann Spagnuolo

    (Center for AIDS Research, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill)

  • Brianna Skinner

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

  • Caroline E. Baker

    (Center for AIDS Research, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill)

  • Craig Sykes

    (University of North Carolina at Chapel Hill)

  • Katie R. Mollan

    (The University of North Carolina Center for AIDS Research)

  • Angela D. M. Kashuba

    (University of North Carolina at Chapel Hill)

  • J. Gerardo García-Lerma

    (National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention)

  • Russell J. Mumper

    (UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill)

  • J. Victor Garcia

    (Center for AIDS Research, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill)

Abstract

Non-adherence to medication is an important health care problem, especially in the treatment of chronic conditions. Injectable long-acting (LA) formulations of antiretrovirals (ARVs) represent a viable alternative to improve adherence to HIV/AIDS treatment and prevention. However, the LA-ARV formulations currently in clinical trials cannot be removed after administration even if adverse events occur. Here we show an ultra-LA removable system that delivers drug for up to 9 months and can be safely removed to stop drug delivery. We use two pre-clinical models for HIV transmission and treatment, non-human primates (NHP) and humanized BLT (bone marrow/liver/thymus) mice and show a single dose of subcutaneously administered ultra-LA dolutegravir effectively delivers the drug in both models and show suppression of viremia and protection from multiple high-dose vaginal HIV challenges in BLT mice. This approach represents a potentially effective strategy for the ultra-LA drug delivery with multiple possible therapeutic applications.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06490-w
    DOI: 10.1038/s41467-018-06490-w
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    Cited by:

    1. 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.
    2. Suyash Deodhar & Brady Sillman & Aditya N. Bade & Sean N. Avedissian & Anthony T. Podany & JoEllyn M. McMillan & Nagsen Gautam & Brandon Hanson & Bhagya L. Dyavar Shetty & Adam Szlachetka & Morgan Joh, 2022. "Transformation of dolutegravir into an ultra-long-acting parenteral prodrug formulation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Manse Kim & Claire E. Johnson & Alan A. Schmalstig & Ayano Annis & Sarah E. Wessel & Brian Horn & Amanda Schauer & Agata A. Exner & Jason E. Stout & Angela Wahl & Miriam Braunstein & J. Victor Garcia , 2022. "A long-acting formulation of rifabutin is effective for prevention and treatment of Mycobacterium tuberculosis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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