{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pons-Faudoa FP"],"funding":["NIAID NIH HHS","NIGMS NIH HHS"],"pagination":["18-27"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10922355"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["366"],"pubmed_abstract":["Treatment nonadherence is a pressing issue in people living with HIV (PLWH), as they require lifelong therapy to maintain viral suppression. Poor adherence leads to antiretroviral (ARV) resistance, transmission to others, AIDS progression, and increased morbidity and mortality. Long-acting (LA) ARV therapy is a promising strategy to combat the clinical drawback of user-dependent dosing. Islatravir (ISL) is a promising candidate for HIV treatment given its long half-life and high potency. Here we show constant ISL release from a subdermal LA nanofluidic implant achieves viral load reduction in SHIV-infected macaques. Specifically, a mean delivery dosage of 0.21 ± 0.07 mg/kg/day yielded a mean viral load reduction of -2.30 ± 0.53 log<sub>10</sub> copies/mL at week 2, compared to baseline. The antiviral potency of the ISL delivered from the nanofluidic implant was higher than oral ISL dosed either daily or weekly. At week 3, viral resistance to ISL emerged in 2 out of 8 macaques, attributable to M184V mutation, supporting the need of combining ISL with other ARV for HIV treatment. The ISL implant produced moderate reactivity in the surrounding tissue, indicating tolerability. Overall, we present the ISL subdermal implant as a promising approach for LA ARV treatment in PLWH."],"journal":["Journal of controlled release : official journal of the Controlled Release Society"],"pubmed_title":["Antiviral potency of long-acting islatravir subdermal implant in SHIV-infected macaques."],"pmcid":["PMC10922355"],"funding_grant_id":["P30 AI161943","R01 AI165372","R01 AI167659","R01 GM127558","HHSN272201100023C","R01 AI120749"],"pubmed_authors":["Pons-Faudoa FP","DeLise A","Sharma S","Di Trani N","Facchi I","Nehete B","Capuani S","Shelton KA","Ittmann MM","Anderson PL","Grattoni A","Wood AM","Kimata JT","Arduino RC","Chua CYX","Bushman LR","Nehete PN"],"additional_accession":[]},"is_claimable":false,"name":"Antiviral potency of long-acting islatravir subdermal implant in SHIV-infected macaques.","description":"Treatment nonadherence is a pressing issue in people living with HIV (PLWH), as they require lifelong therapy to maintain viral suppression. Poor adherence leads to antiretroviral (ARV) resistance, transmission to others, AIDS progression, and increased morbidity and mortality. Long-acting (LA) ARV therapy is a promising strategy to combat the clinical drawback of user-dependent dosing. Islatravir (ISL) is a promising candidate for HIV treatment given its long half-life and high potency. Here we show constant ISL release from a subdermal LA nanofluidic implant achieves viral load reduction in SHIV-infected macaques. Specifically, a mean delivery dosage of 0.21 ± 0.07 mg/kg/day yielded a mean viral load reduction of -2.30 ± 0.53 log<sub>10</sub> copies/mL at week 2, compared to baseline. The antiviral potency of the ISL delivered from the nanofluidic implant was higher than oral ISL dosed either daily or weekly. At week 3, viral resistance to ISL emerged in 2 out of 8 macaques, attributable to M184V mutation, supporting the need of combining ISL with other ARV for HIV treatment. The ISL implant produced moderate reactivity in the surrounding tissue, indicating tolerability. Overall, we present the ISL subdermal implant as a promising approach for LA ARV treatment in PLWH.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-06-01T05:45:49.349Z","creation":"2025-04-06T22:10:10.872Z"},"accession":"S-EPMC10922355","cross_references":{"pubmed":["38142963"],"doi":["10.1016/j.jconrel.2023.12.031"]}}