{"doi":"10.1002/jia2.26507","title":"Effectiveness of islatravir post‐exposure prophylaxis after intravenous challenge with simian immunodeficiency virus in rhesus macaques","abstract":"INTRODUCTION: Islatravir (ISL) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) with robust antiretroviral activity. The efficacy of ISL administered for post-exposure prophylaxis (PEP) was evaluated in a simian immunodeficiency virus (SIV) rhesus macaque intravenous (IV) challenge model. METHODS: Twelve rhesus macaques were challenged with SIVmac251 via IV administration. After 24 hours, six animals received ISL 3.9 mg/kg (the minimum effective dose that gives maximal protection) and six animals were untreated controls. In stage 1, treated animals received 4 weekly oral doses of ISL and were monitored for SIV infection for 7 weeks after the last dose. In stage 2, uninfected, treated animals from stage 1 were challenged similarly; 24 hours after challenge, 3 weekly oral doses of ISL 3.9 mg/kg were initiated. The treated animals were monitored for 7 weeks, as in stage 1. Uninfected, treated animals (from stage 2) entered stage 3. In stage 3, the animals were challenged as in stage 2; 24 hours after challenge, 2 weekly oral doses of ISL 3.9 mg/kg were initiated. The treated animals were monitored for 7 weeks, as before. Finally, in stage 4, uninfected, treated animals were challenged using IV administration and 24 hours later were treated with a single oral dose of ISL 3.9 mg/kg and monitored for 7 weeks. Infection was monitored through plasma viral RNA and proviral DNA amplification. Virus-specific antibody responses were measured using a commercial assay. ISL concentrations in plasma and ISL triphosphate (ISL-TP) levels in peripheral blood mononuclear cells were measured longitudinally. RESULTS: All untreated controls were viraemic 7 days after SIVmac251 IV challenge. All six ISL-treated animals were completely protected in stages 1-3 (Fisher exact test p = 0.0022). In stage 4, two of six ISL-treated animals became infected with wild-type SIVmac251: viraemia was observed at days 14 and 49 in the two animals (Fisher exact test p = 0.06). Both animals had unquantifiable ISL-TP on the day viraemia was observed. CONCLUSIONS: Two weekly oral doses of ISL 3.9 mg/kg, administered 24 hours post IV SIV exposure, prevents infection of rhesus macaques. These results support further investigation of a long-acting oral NRTTI for PEP.","journal":"Journal of the International AIDS Society","year":2025,"id":568770,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9629,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":161889,"name":"Agegnehu Gettie","orcid":null,"position":1,"is_corresponding":false},{"id":1473900,"name":"Leslie St. Bernard","orcid":null,"position":2,"is_corresponding":false},{"id":388373,"name":"Brooke Grasperge","orcid":"0000-0002-1262-6217","position":3,"is_corresponding":false},{"id":63815,"name":"Ryan Vargo","orcid":null,"position":4,"is_corresponding":false},{"id":785820,"name":"Michelle Pham","orcid":"0000-0002-4795-0930","position":5,"is_corresponding":false},{"id":1473901,"name":"Kerry L. Fillgrove","orcid":null,"position":6,"is_corresponding":false},{"id":1473902,"name":"Neal Dube","orcid":null,"position":7,"is_corresponding":false},{"id":1473569,"name":"Tracy L. Diamond","orcid":"0000-0002-4672-8641","position":8,"is_corresponding":false},{"id":263026,"name":"Daria J. Hazuda","orcid":"0000-0002-6894-1056","position":9,"is_corresponding":false},{"id":1473903,"name":"Jay A. Grobler","orcid":null,"position":10,"is_corresponding":false},{"id":524564,"name":"Martin Markowitz","orcid":null,"position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-19T02:56:55.795846Z","pmid":"40534150","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":[]}