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 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 62.50% 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.
Original language | English (US) |
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Article number | 2000163 |
Pages (from-to) | 2000163 |
Number of pages | 1 |
Journal | advanced therapeutics |
Volume | 4 |
Issue number | 3 |
Early online date | Dec 16 2020 |
DOIs | |
State | Published - Mar 2021 |
Keywords
- drug delivery
- HIV pre-exposure prophylaxis
- implantable devices
- nanofluidics
- tenofovir alafenamide
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Pharmacology
- Pharmaceutical Science
- Genetics(clinical)
- Biochemistry, medical
- Pharmacology (medical)