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

作者：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 Ittmann, Joan E. Nichols, Jason T. Kimata, Peter L. Anderson, Pramod N. Nehete, Roberto C. Arduino, Alessandro Grattoni · 发表于：Science Translational Medicine · 年份：2023 · DOI：10.1126/scitranslmed.adg2887 · 被引用次数：24 · 研究领域：HIV Research and Treatment、HIV/AIDS Research and Interventions、HIV/AIDS drug development and treatment

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 6 cells) for more than 20 months. These drug concentrations were above the established PrEP protection threshold. In two unblinded, placebo-controlled studies, islatravir-eluting implants conferred 100% protection against infection with SHIV SF162P3 after repeated low-dose rectal or vaginal challenge in male or female rhesus macaques, respectively, compared to placebo control groups. The islatravir-eluting implants were well tolerated with mild local tissue inflammation and no signs of systemic toxicity over the 20-month study period. This refillable islatravir-eluting implant has potential as a long-acting drug delivery system for HIV PrEP.