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Ultra-long-acting injectable, biodegradable, and removable in-situ forming implant with cabotegravir for HIV prevention
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Safety, Pharmacokinetics, and Degradation of Ultra-Long-Acting Injectable, Biodegradable, and Removable In-Situ Forming Implant with Cabotegravir for HIV Prevention HIV4RP 2024
CROI: Pharmacokinetics and X-ray Imaging of Long-acting Cabotegravir In Situ Forming Implant
PHARMACOKINETICS AND XRAY IMAGING OF LONG-ACTING CABOTEGRAVIR IN SITU FORMING IMPLANT (ABSTRACT 991)
Isabella Young
University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
https://www.croiwebcasts.org/console/player/51903?mediaType=slideVideo&
Journal of Controlled Release
10 October 2025
Abstract
HIV is a global health issue affecting approximately 40 million people worldwide, with low patient adherence being the primary challenge for maintaining effective pre-exposure prophylaxis (PrEP). Limitations of oral PrEP are mainly attributed to lack of adherence due to pill fatigue or stigma [1, 2]. Recently introduced long-acting injectables offer several advantages over daily PrEP, namely by improving adherence and improving efficacy [3-5]. The approved long-acting injectable Apretude® is administered every two months and elicits a long pharmacokinetic tail of >15 months that can lead to potential drug-resistant virus [6]. To address these limitations, we report on an ultra-long-acting injectable cabotegravir/barium sulfate (CAB/BaSO₄) in-situ forming implant (ISFI) capable of maintaining therapeutic CAB concentrations (
4 PA-IC90) for up to 390 days. In this work, we optimized the ISFI formulation to include a contrast agent, BaSO4, to assess in vivo depot visualization and migration using X-ray imaging. CAB/BaSO4 ISFIs were investigated in vitro to determine CAB release kinetics, and in vivo to assess safety and pharmacokinetics in BALB/c mice. The CAB/BaSO₄ ISFI was well-tolerated and showed minimal to moderate signs of local inflammation and none to minimal systemic inflammation. At 24 hours post removal of the CAB/BaSO₄ ISFI, CAB plasma concentrations reached below the 1PA-IC90 benchmark and below the limit of quantification within 14 days for 5 out of 6 mice. A full biodistribution study showed that CAB was mainly localized at the injection site subcutaneous tissue and plasma, with no detectable concentrations in other organs. Whole-body X-ray imaging showed that implants were visible for up to 268 days post administration with no noticeable migration. This is the first report of a CAB/BaSO₄ ISFI that is imageable, ultra-long-acting (>180 days), biodegradable, and removable, that can potentially revolutionize current HIV PrEP and help curb the global HIV epidemic.
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