Changes in local tissue microenvironment in response to subcutaneous long-acting delivery of tenofovir alafenamide in rats and non-human primates

Authors

Fernanda P Pons-Faudoa
Nicola Di Trani
Simone Capuani
Nathanael Hernandez
Anthony M Wood
Bharti Nehete
Jean Niles
Kathryn A Shelton
Sarah Kezar
Lane R Bushman
Corrine Ying Xuan Chua
Michael M Ittmann
Peter L Anderson
Pramod N Nehete
Roberto C Arduino
Joan E Nichols
Alessandro Grattoni

Publication Date

6-1-2023

Journal

Journal of Controlled Release

Abstract

Several implantable long-acting (LA) delivery systems have been developed for sustained subcutaneous administration of tenofovir alafenamide (TAF), a potent and effective nucleotide reverse transcriptase inhibitor used for HIV pre-exposure prophylaxis (PrEP). LA platforms aim to address the lack of adherence to oral regimens, which has impaired PrEP efficacy. Despite extensive investigations in this field, tissue response to sustained subcutaneous TAF delivery remains to be elucidated as contrasting preclinical results have been reported in the literature. To this end, here we studied the local foreign body response (FBR) to sustained subdermal delivery of three forms of TAF, namely TAF free base (TAF

Keywords

Rats, Animals, Tenofovir, Anti-HIV Agents, HIV Infections, Macaca mulatta, Rats, Sprague-Dawley, Adenine, Alanine