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

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.
Authors	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, Russell J Mumper, J Victor Garcia
Journal	Nature communications (Nat Commun) Vol. 9 Issue 1 Pg. 4156 (10 08 2018) ISSN: 2041-1723 [Electronic] England
PMID	30297889 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Anti-HIV Agents Heterocyclic Compounds, 3-Ring Oxazines Piperazines Pyridones dolutegravir
Topics	Animals Anti-HIV Agents (administration & dosage, pharmacokinetics, therapeutic use) Disease Models, Animal Drug Delivery Systems (methods) HIV Infections (drug therapy, prevention & control, virology) HIV-1 (drug effects, genetics, physiology) Heterocyclic Compounds, 3-Ring (administration & dosage, pharmacokinetics, therapeutic use) Humans Macaca mulatta Mice, Inbred NOD Mice, Knockout Mice, SCID Oxazines Piperazines Pyridones Time Factors Tissue Distribution Virus Replication (drug effects, genetics)

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