Preventive Efficacy of a Tenofovir Alafenamide Fumarate Nanofluidic Implant in SHIV-Challenged Nonhuman Primates

Pre-exposure prophylaxis (PrEP) using antiretroviral oral drugs is effective at preventing human immunodeficiency virus (HIV) transmission when individuals adhere to the dosing regimen. Tenofovir alafenamide (TAF) is a potent antiretroviral drug, with numerous long-acting (LA) delivery systems under development to improve PrEP adherence. However, none has undergone preventive efficacy assessment. Here it is shown that LA TAF using a novel subcutaneous nanofluidic implant (nTAF) confers partial protection from HIV transmission. It is demonstrated that sustained subcutaneous delivery through nTAF in rhesus macaques maintains tenofovir diphosphate concentration at a median of 390 fmol per 106 peripheral blood mononuclear cells, nine times above clinically protective levels. In a non-blinded, placebo-controlled rhesus macaque study with repeated low-dose rectal simian HIVSF162P3 (SHIVSF162P3) challenge, the nTAF cohort has a 62.5095 1.72–85.69 p = 0.068) in risk of infection per exposure compared to the control. This finding mirrors that of tenofovir disoproxil fumarate (TDF) monotherapy, where 60 and clinically, 676 this nanofluidic technology shows potential as a subcutaneous delivery platform for long-term PrEP and provides insights for clinical implementation of LA TAF for HIV prevention.