@article{98cedffee52e4b27b1f72a51eb75a463,
title = "Viral load reduction in SHIV-positive nonhuman primates via long-acting subcutaneous tenofovir alafenamide fumarate release from a nanofluidic implant",
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-na{\"i}ve 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.",
keywords = "HIV treatment, Implantable drug delivery, Long-acting TAF, TAF monotherapy, Viral load",
author = "Pons-Faudoa, {Fernanda P.} and {Di Trani}, Nicola and Antons Sizovs and Shelton, {Kathryn A.} and Zoha Momin and Bushman, {Lane R.} and Jiaqiong Xu and Lewis, {Dorothy E.} and Sandra Demaria and Trevor Hawkins and Rooney, {James F.} and Marzinke, {Mark A.} and Kimata, {Jason T.} and Anderson, {Peter L.} and Nehete, {Pramod N.} and Arduino, {Roberto C.} and {Jagannadha Sastry}, K. and Alessandro Grattoni",
note = "Funding Information: Funding: This research was funded by the National Institutes of Health National Institute of Allergy and Infectious Diseases (R01AI120749; A.G.) and Gilead Sciences (A.G.). The development of the nanochannel membrane used in the studies was funded by the National Institutes of Health National Institute of General Medical Sciences (R01GM127558; A.G.). F.P.P.-F. received funding support from Tecnologico de Monterrey and Consejo Nacional de Ciencia y Tecnologia. Funding Information: This research was funded by the National Institutes of Health National Institute of Allergy and Infectious Diseases (R01AI120749; A.G.) and Gilead Sciences (A.G.). The development of the nanochannel membrane used in the studies was funded by the National Institutes of Health National Institute of General Medical Sciences (R01GM127558; A.G.). F.P.P.-F. received funding support from Tecnologico de Monterrey and Consejo Nacional de Ciencia y Tecnologia. We thank Andreana L. Rivera, Yuelan Ren and Sandra Steptoe from the research pathology core of Houston Methodist Research Institute. Jianhua ?James? Gu from the electron microscopy core. We thank Simone Capuani from the Houston Methodist Research Institute for implant design and Dixita Viswanath for help with tissue dissection. We thank Luke Segura, Elizabeth Lindemann and Greg Wilkerson from the Michael E. Keeling Center for Comparative medicine and Research at UTMDACC for support in animal studies and Bharti Nehete for plasma and PBMC isolation. TAF fumarate was provided by Gilead Sciences, Inc. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = oct,
doi = "10.3390/pharmaceutics12100981",
language = "English (US)",
volume = "12",
pages = "1--16",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "10",
}