| Title: |
Viral load Reduction in SHIV-Positive Nonhuman Primates via Long-Acting Subcutaneous Tenofovir Alafenamide Fumarate Release from a Nanofluidic Implant |
| Authors: |
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 |
| Source: |
Pharmaceutics, Vol 12, Iss 981, p 981 (2020) |
| Publisher Information: |
MDPI AG |
| Publication Year: |
2020 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
HIV treatment; implantable drug delivery; viral load; TAF monotherapy; long-acting TAF; Pharmacy and materia medica; RS1-441 |
| Description: |
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 6 cells (IQR, 243.0 to 509.0 fmol/10 6 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 10 copies/mL (95% CI, −0.30 to −2.23 log 10 copies/mL), similar to −1.08 log 10 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://www.mdpi.com/1999-4923/12/10/981; https://doaj.org/toc/1999-4923; https://doaj.org/article/bc54b683a78a4c54871a1a7b1e376c61 |
| DOI: |
10.3390/pharmaceutics12100981 |
| Availability: |
https://doi.org/10.3390/pharmaceutics12100981; https://doaj.org/article/bc54b683a78a4c54871a1a7b1e376c61 |
| Accession Number: |
edsbas.7ABAAC44 |
| Database: |
BASE |