Preventive Efficacy of a Tenofovir Alafenamide Fumarate Nanofluidic Implant in SHIV‐Challenged Nonhuman Primates
Fernanda P. Pons‐Faudoa, Antons Sizovs, Kathryn A. Shelton, Zoha Momin, Jean A. Niles, Lane R. Bushman, Jiaqiong Xu, Corrine Ying Xuan Chua, Joan E. Nichols, Sandra Demaria, Michael Ittmann, Trevor Hawkins, James F. Rooney, Mark A. Marzinke, Jason T. Kimata, Peter L. Anderson, Pramod N. Nehete, Roberto C. Arduino, Mauro Ferrari, K. Jagannadha Sastry, Alessandro Grattoni
Abstract
Abstract 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 10 6 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 HIV SF162P3 (SHIV SF162P3 ) challenge, the nTAF cohort has a 62.50% reduction (95% CI: 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% protective efficacy is observed in macaques, and clinically, 67% reduction in risk with 86% preventive efficacy in individuals with detectable drug in the plasma. Overall, 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.