{"doi":"10.3390/pharmaceutics12100981","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-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/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.","journal":"Pharmaceutics","year":2020,"id":54362,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":105,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9485,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":279015,"name":"Nicola Di Trani","orcid":"0000-0002-4780-7915","position":1,"is_corresponding":false},{"id":279016,"name":"Antons Sizovs","orcid":"0000-0001-6495-6317","position":2,"is_corresponding":false},{"id":279017,"name":"Kathryn A. Shelton","orcid":"0000-0002-1754-1423","position":3,"is_corresponding":false},{"id":279018,"name":"Zoha Momin","orcid":"0000-0002-2247-7665","position":4,"is_corresponding":false},{"id":280276,"name":"Lane R. Bushman","orcid":null,"position":5,"is_corresponding":false},{"id":279019,"name":"Jiaqiong Xu","orcid":"0000-0002-3463-2327","position":6,"is_corresponding":false},{"id":117072,"name":"Dorothy E. Lewis","orcid":null,"position":7,"is_corresponding":false},{"id":245473,"name":"Sandra Demaria","orcid":"0000-0003-4426-0499","position":8,"is_corresponding":false},{"id":280277,"name":"Trevor Hawkins","orcid":null,"position":9,"is_corresponding":false},{"id":255291,"name":"James F. Rooney","orcid":"0000-0003-3261-0711","position":10,"is_corresponding":false},{"id":279020,"name":"Mark A. Marzinke","orcid":"0000-0003-1670-8786","position":11,"is_corresponding":false},{"id":279021,"name":"Jason T. Kimata","orcid":"0000-0002-0504-0090","position":12,"is_corresponding":false},{"id":279022,"name":"Peter L. Anderson","orcid":"0000-0002-1200-8494","position":13,"is_corresponding":false},{"id":279023,"name":"Pramod N. Nehete","orcid":"0000-0002-2815-2677","position":14,"is_corresponding":false},{"id":279024,"name":"Roberto C. Arduino","orcid":"0000-0002-7381-844X","position":15,"is_corresponding":false},{"id":279025,"name":"K. Jagannadha Sastry","orcid":"0000-0002-6987-4422","position":16,"is_corresponding":false},{"id":279026,"name":"Alessandro Grattoni","orcid":"0000-0001-7888-422X","position":17,"is_corresponding":false},{"id":279014,"name":"Fernanda P. Pons‐Faudoa","orcid":"0000-0002-5135-9481","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-18T21:03:43.037640Z","pmid":"33080776","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}