𝐖𝐞 𝐜𝐮𝐫𝐫𝐞𝐧𝐭𝐥𝐲 𝐡𝐚𝐯𝐞 𝐚𝐧 𝐨𝐩𝐞𝐧 𝐏𝐡𝐃 𝐩𝐨𝐬𝐢𝐭𝐢𝐨𝐧 𝐢𝐧 𝐭𝐡𝐞 𝐥𝐚𝐛. 𝐈𝐧𝐭𝐞𝐫𝐞𝐬𝐭𝐞𝐝? 𝐂𝐥𝐢𝐜𝐤 𝐜𝐨𝐧𝐭𝐚𝐜𝐭 𝐭𝐨 𝐠𝐞𝐭 𝐬𝐭𝐚𝐫𝐭𝐞𝐝.
𝐖𝐞 𝐜𝐮𝐫𝐫𝐞𝐧𝐭𝐥𝐲 𝐡𝐚𝐯𝐞 𝐚𝐧 𝐨𝐩𝐞𝐧 𝐏𝐡𝐃 𝐩𝐨𝐬𝐢𝐭𝐢𝐨𝐧 𝐢𝐧 𝐭𝐡𝐞 𝐥𝐚𝐛. 𝐈𝐧𝐭𝐞𝐫𝐞𝐬𝐭𝐞𝐝? 𝐂𝐥𝐢𝐜𝐤 𝐜𝐨𝐧𝐭𝐚𝐜𝐭 𝐭𝐨 𝐠𝐞𝐭 𝐬𝐭𝐚𝐫𝐭𝐞𝐝.

Transcutaneously refillable nanofluidic implant achieves sustained level of tenofovir diphosphate for HIV pre-exposure prophylaxis

Chua CYX, Jain P, Ballerini A, Bruno G, Hood RL, Gupte M, Gao S, Di Trani N, Susnjar A, Shelton K, Bushman LR, Folci M, Filgueira CS, Marzinke MA, Anderson PL, Hu M, Nehete P, Arduino RC, Sastry JK, Grattoni A.

Abstract

Pre-exposure prophylaxis (PrEP) with antiretroviral (ARV) drugs are effective at preventing human immunodeficiency virus (HIV) transmission. However, implementation of PrEP presents significant challenges due to poor user adherence, low accessibility to ARVs and multiple routes of HIV exposure. To address these challenges, we developed the nanochannel delivery implant (NDI), a subcutaneously implantable device for sustained and constant delivery of tenofovir alafenamide (TAF) and emtricitabine (FTC) for HIV PrEP. Unlike existing drug delivery platforms with finite depots, the NDI incorporates ports allowing for transcutaneous refilling upon drug exhaustion. NDI-mediated drug delivery in rhesus macaques resulted in sustained release of both TAF and FTC for 83 days, as indicated by concentrations of TAF, FTC and their respectively metabolites in plasma, PBMCs, rectal mononuclear cells and tissues associated with HIV transmission. Notably, clinically relevant preventative levels of tenofovir diphosphate were achieved as early as 3 days after NDI implantation. We also demonstrated the feasibility of transcutaneous drug refilling to extend the duration of PrEP drug delivery in NHPs. Overall, the NDI represents an innovative strategy for long-term HIV PrEP administration in both developed and developing countries.