Long-acting refillable nanofluidic implant confers protection against SHIV infection in nonhuman primates

Authors: Fernanda P. Pons-Faudoa, Nicola Di Trani, Simone Capuani, Jocelyn Nikita Campa-Carranza, Bharti Nehete, Suman Sharma, Kathryn A. Shelton, Lane R. Bushman, Farah Abdelmawla, Martin Williams, Laura Roon, David Nerguizian, Corrine Ying Xuan Chua, Michael M. Ittmann, Joan E. Nichols, Jason T. Kimata, Peter L. Anderson, Pramod N. Nehete, Roberto C. Arduino, Alessandro Grattoni

Published: 2023-06-28

DOI: 10.1126/scitranslmed.adg2887

Source: Full article


Abstract

The impact of pre-exposure prophylaxis (PrEP) on slowing the global HIV epidemic hinges on effective drugs and delivery platforms. Oral drug regimens are the pillar of HIV PrEP, but variable adherence has spurred development of long-acting delivery systems with the aim of increasing PrEP access, uptake, and persistence. We have developed a long-acting subcutaneous nanofluidic implant that can be refilled transcutaneously for sustained release of the HIV drug islatravir, a nucleoside reverse transcriptase translocation inhibitor that is used for HIV PrEP. In rhesus macaques, the islatravir-eluting implants achieved constant concentrations of islatravir in plasma (median 3.14 nM) and islatravir triphosphate in peripheral blood mononuclear cells (median 0.16 picomole per 10