Preventive Efficacy of a Tenofovir Alafenamide Fumarate Nanofluidic Implant in SHIV‐Challenged Nonhuman Primates. Issue 3 (16th December 2020)

• Record Type: Journal Article
• Authors: Pons‐Faudoa, Fernanda P.; Sizovs, Antons; Shelton, Kathryn A.; Momin, Zoha; Niles, Jean A.; Bushman, Lane R.; Xu, Jiaqiong; Chua, Corrine Ying Xuan; Nichols, Joan E.; Demaria, Sandra; Ittmann, Michael M.; Hawkins, Trevor; Rooney, James F.; Marzinke, Mark A.; Kimata, Jason T.; Anderson, Peter L.; Nehete, Pramod N.; Arduino, Roberto C.; Ferrari, Mauro; Sastry, K. Jagannadha; Grattoni, Alessandro
• Is Part Of: Advanced therapeutics. Volume 4:Issue 3(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-16
• Subjects: drug delivery -- HIV pre‐exposure prophylaxis -- implantable devices -- nanofluidics -- tenofovir alafenamide; Therapeutics -- Periodicals; Pharmaceutical technology -- Periodicals; Pharmacogenetics -- Periodicals; 615.5
• DOI: 10.1002/adtp.202000163
• Languages: English
• ISSNs: 2366-3987

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 HIVSF162P3 (SHIVSF162P3 ) 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. Abstract : The first HIV pre‐exposure prophylaxis (PrEP) assessment of an implantable long‐acting antiretroviral platform is performed. In this study, the partial protection of simian HIV with tenofovir alafenamide (TAF) delivered by a nanofluidic implant is demonstrated in nonhuman primates.