Abstract
PurposeSexual transmission of HIV has been clinically proven to be preventable with a once-daily oral tablet; however, missed doses dramatically increase the risk of HIV infection. Long-acting subcutaneous implants do not allow the user to miss a dose. A desirable long-acting drug-eluting implant can deliver a constant amount of drug, adjust the delivered dose, and be readily manufactured. We present a long-acting, subcutaneous implant design composed of tenofovir alafenamide hemifumarate (TAF) pellets loaded in a sealed polyether urethane tube for the prevention of HIV transmission.MethodsImplants were prepared with pressed drug pellets and extruded polyurethane tubing. In vitro release rate of implants using different pellet formulations, rate-controlling membranes, and geometries were measured.ResultsTenofovir alafenamide release appeared to be governed by a pseudo-steady state and followed a mass transport model of release from a cylindrical drug reservoir. Implant seal integrity was tested and confirmed using mechanical testing. The inclusion of sodium chloride in the pellet increased the release rate and reduced initial lag. The release was sustained for 100 days.ConclusionsThe release rate of tenofovir alafenamide mechanistically varied with geometry and rate controlling membrane composition. The polyether urethane implant presented herein is modular and tunable to adjust the release rate and duration of the TAF release.
Highlights
In 2017, 36.9 million people globally were living with HIV infection, and 1.8 million people were newly infected [1]
The actual amounts released are higher than what we report as the released tenofovir alafenamide hydrolyzes in the external IVRT media while the sample is waiting to be collected
In our first attempts at making Page of 83 urethanes (PEU) based tenofovir alafenamide hemifumarate (TAF) implants, we found that the implants had osmotically swelled, causing implants made by multiple sealing techniques to fail
Summary
In 2017, 36.9 million people globally were living with HIV infection, and 1.8 million people were newly infected [1]. In 2016, the Political Declaration on Ending AIDS set an ambitious goal of reducing new infections by 75% by 2020, and have achieved a 16% decrease in new infections from 2010 to 2017 [2]. To accomplish this reduction of HIV transmission, the development of new technologies to stop sexual transmission will be critical. The use of antiretrovirals (ARV) for pre-exposure prophylaxis (PrEP) will be a key prevention strategy in reducing HIV acquisition in high-risk populations and quicken the pace of reducing new infections [3]. Dosing regimens ranging from once weekly to once monthly or yearly are being considered in the HIV prevention field [10]
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