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Nat Commun. 2018 Oct 8;9(1):4156. doi: 10.1038/s41467-018-06490-w.

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

Author information

1
Division of Infectious Diseases, Center for AIDS Research, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, 120 Mason Farm Rd. CB 7042, Chapel Hill, NC 27599, USA. kovarovm@med.unc.edu.
2
Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 125 Mason Farm Rd. 4205, Chapel Hill, NC 27599, USA.
3
Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Rd, MS G45, Atlanta, GA 30329, USA.
4
Division of Infectious Diseases, Center for AIDS Research, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, 120 Mason Farm Rd. CB 7042, Chapel Hill, NC 27599, USA.
5
Comparative Medicine Branch, Division of Scientific Resources, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
6
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 120 Mason Farm Rd. CB#7361, Chapel Hill, NC 27599, USA.
7
The University of North Carolina Center for AIDS Research, 3126 McGavran-Greenberg Hall, Chapel Hill, NC 27599, USA.
8
Division of Infectious Diseases, Center for AIDS Research, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, 120 Mason Farm Rd. CB 7042, Chapel Hill, NC 27599, USA. victor_garcia@med.unc.edu.

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.

PMID:
30297889
PMCID:
PMC6175887
DOI:
10.1038/s41467-018-06490-w
[Indexed for MEDLINE]
Free PMC Article

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