Antiviral Potency of Long-Acting Islatravir Subdermal Implant In SHIV-Infected Macaques

Authors

Fernanda P Pons-Faudoa
Nicola Di Trani
Simone Capuani
Ilaria Facchi
Anthony M Wood
Bharti Nehete
Ashley DeLise
Suman Sharma
Kathryn A Shelton
Lane R Bushman
Corrine Ying Xuan Chua
Michael M Ittmann
Jason T Kimata
Peter L Anderson
Pramod N Nehete
Roberto C Arduino
Alessandro Grattoni

Publication Date

2-1-2024

Journal

Journal of Controlled Release

Abstract

Treatment nonadherence is a pressing issue in people living with HIV (PLWH), as they require lifelong therapy to maintain viral suppression. Poor adherence leads to antiretroviral (ARV) resistance, transmission to others, AIDS progression, and increased morbidity and mortality. Long-acting (LA) ARV therapy is a promising strategy to combat the clinical drawback of user-dependent dosing. Islatravir (ISL) is a promising candidate for HIV treatment given its long half-life and high potency. Here we show constant ISL release from a subdermal LA nanofluidic implant achieves viral load reduction in SHIV-infected macaques. Specifically, a mean delivery dosage of 0.21 ± 0.07 mg/kg/day yielded a mean viral load reduction of -2.30 ± 0.53 log

Keywords

Animals, Humans, Anti-HIV Agents, Macaca, HIV Infections, Deoxyadenosines, Anti-Retroviral Agents

DOI

10.1016/j.jconrel.2023.12.031

PMID

38142963

PMCID

PMC10922355

PubMedCentral® Posted Date

February 2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes