Viral load Reduction in SHIV-Positive Nonhuman Primates via Long-Acting Subcutaneous Tenofovir Alafenamide Fumarate Release from a Nanofluidic Implant

Fernanda P Pons-Faudoa, Nicola Di Trani, Antons Sizovs, Kathryn A Shelton, Zoha Momin, Lane R Bushman, Jiaqiong Xu, Dorothy E Lewis, Sandra Demaria, Trevor Hawkins, James F Rooney, Mark A Marzinke, Jason T Kimata, Peter L Anderson, Pramod N Nehete, Roberto C Arduino, K Jagannadha Sastry, Alessandro Grattoni

Research output: Contribution to journalArticlepeer-review

Abstract

HIV-1 is a chronic disease managed by strictly adhering to daily antiretroviral therapy (ART). However, not all people living with HIV-1 have access to ART, and those with access may not adhere to treatment regimens increasing viral load and disease progression. Here, a subcutaneous nanofluidic implant was used as a long-acting (LA) drug delivery platform to address these issues. The device was loaded with tenofovir alafenamide (TAF) and implanted in treatment-naïve simian HIV (SHIV)-positive nonhuman primates (NHP) for a month. We monitored intracellular tenofovir-diphosphate (TFV-DP) concentration in the target cells, peripheral blood mononuclear cells (PBMC). The concentrations of TFV-DP were maintained at a median of 391.0 fmol/106 cells (IQR, 243.0 to 509.0 fmol/106 cells) for the duration of the study. Further, we achieved drug penetration into lymphatic tissues, known for persistent HIV-1 replication. Moreover, we observed a first-phase viral load decay of -1.14 ± 0.81 log10 copies/mL (95% CI, -0.30 to -2.23 log10 copies/mL), similar to -1.08 log10 copies/mL decay observed in humans. Thus, LA TAF delivered from our nanofluidic implant had similar effects as oral TAF dosing with a lower dose, with potential as a platform for LA ART.

Original languageEnglish (US)
JournalPharmaceutics
Volume12
Issue number10
DOIs
StatePublished - Oct 17 2020

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