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

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 impl...

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Main Authors: Fernanda P. Pons-Faudoa (Author), Nicola Di Trani (Author), Antons Sizovs (Author), Kathryn A. Shelton (Author), Zoha Momin (Author), Lane R. Bushman (Author), Jiaqiong Xu (Author), Dorothy E. Lewis (Author), Sandra Demaria (Author), Trevor Hawkins (Author), James F. Rooney (Author), Mark A. Marzinke (Author), Jason T. Kimata (Author), Peter L. Anderson (Author), Pramod N. Nehete (Author), Roberto C. Arduino (Author), K. Jagannadha Sastry (Author), Alessandro Grattoni (Author)
Format: Book
Published: MDPI AG, 2020-10-01T00:00:00Z.
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Summary: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<sup>6</sup> cells (IQR, 243.0 to 509.0 fmol/10<sup>6</sup> 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<sub>10</sub> copies/mL (95% CI, −0.30 to −2.23 log<sub>10</sub> copies/mL), similar to −1.08 log<sub>10</sub> 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.
Item Description:10.3390/pharmaceutics12100981
1999-4923

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