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 journalArticle

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)
Article number981
Pages (from-to)1-16
Number of pages16
JournalPharmaceutics
Volume12
Issue number10
DOIs
StatePublished - Oct 2020

Keywords

  • HIV treatment
  • Implantable drug delivery
  • Long-acting TAF
  • TAF monotherapy
  • Viral load

ASJC Scopus subject areas

  • Pharmaceutical Science

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