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

• Published in: Pharmaceutics Vol. 12; no. 10; p. 981
• Main Authors: Pons-Faudoa, Fernanda P, Trani, Nicola Di, Sizovs, Antons, Shelton, Kathryn A, Momin, Zoha, Bushman, Lane R, Xu, Jiaqiong, Lewis, Dorothy E, Demaria, Sandra, Hawkins, Trevor, Rooney, James F, Marzinke, Mark A, Kimata, Jason T, Anderson, Peter L, Nehete, Pramod N, Arduino, Roberto C, Sastry, K Jagannadha, Grattoni, Alessandro
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.10.2020; MDPI
• Subjects: Animal welfare; Drug delivery systems; Drug dosages; Euthanasia; HIV; HIV treatment; Human immunodeficiency virus; implantable drug delivery; Infections; Laboratory animals; long-acting TAF; Membranes; Plasma etching; Scanning electron microscopy; Silicon; TAF monotherapy; Transplants & implants; Viral infections; viral load; United States > US; HIV treatment; viral load; long-acting TAF; TAF monotherapy; implantable drug delivery
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics12100981

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/10 cells (IQR, 243.0 to 509.0 fmol/10 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 log copies/mL (95% CI, -0.30 to -2.23 log copies/mL), similar to -1.08 log 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.