{"doi":"10.1093/jac/dkaf449","title":"Model-based assessment of VRC07-523LS dosing in infants through population pharmacokinetic -pharmacodynamic modelling in adults and infants","abstract":"OBJECTIVES: To develop a population pharmacokinetic (popPK) model to understand factors affecting the broadly neutralizing HIV antibody (bNAb) VR07-523LS disposition and infant predicted serum neutralization 80% inhibitory dilution titre ratio (PT80) and its potential relationship to antiviral effects. METHODS: PK data from two studies were used: infants exposed to HIV initiating therapy ≤5 days of age (IMPAACT P1112, n = 21) and healthy adults (VRC605, n = 25). The infant study implemented fixed subcutaneous (s.c.) dosing whereas the adult study implemented weight-based dosing, via both intravenous (i.v.) and s.c. routes. Monte Carlo simulation assessed two doses (80 mg followed by 100 mg at 12 weeks) to determine the maintenance of levels >10 µg/mL in virtual infants. The broadly neutralizing antibodies (bNAbs) concentration/IC80 ratio (PT80) was calculated on the basis of simulated concentrations from the popPK model and VRC07-523LS HIV-1 sensitivity (IC80) distribution. RESULTS: This model predicts typical infant CL/F and t1/2 of 159 mL/day/70 kg and 39 days. Comparatively, predicted adult typical CL/F and t1/2 were 269 mL/day/70 kg and 31 days. Concentrations were >10 µg/mL in >87% of virtual infants at 12 weeks following one dose and >98% at 24 weeks following two doses. Median (90% predictive interval) PT80 was 163 (71-383), 116 (51-274) and 61 (26-144) at 6, 8 and 12 weeks, respectively. Significant model covariates included age (infant versus adult) and multiple dosing. CONCLUSIONS: Age and repeat dosing influence VRC07-523LS PK. An 80-mg dose followed by 100 mg at 12 weeks rapidly achieves and maintains concentrations >10 µg/mL for >24 weeks. This dosing strategy is expected to result in antiviral effects in patients with sensitive viruses and supports further evaluation of VRC07-523LS.","journal":"Journal of Antimicrobial Chemotherapy","year":2025,"id":549872,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.76,"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":108758,"name":"Mina Nikanjam","orcid":"0000-0001-7052-6348","position":1,"is_corresponding":false},{"id":325730,"name":"Coleen K. Cunningham","orcid":"0000-0002-7725-3052","position":2,"is_corresponding":false},{"id":1445260,"name":"Elizabeth J McFarland","orcid":null,"position":3,"is_corresponding":false},{"id":349133,"name":"Petronella Muresan","orcid":null,"position":4,"is_corresponding":false},{"id":349134,"name":"Charlotte Perlowski","orcid":null,"position":5,"is_corresponding":false},{"id":1445261,"name":"Dwight E Yin","orcid":null,"position":6,"is_corresponding":false},{"id":346911,"name":"Jack Moye","orcid":"0000-0001-9976-8586","position":7,"is_corresponding":false},{"id":1445262,"name":"Hans B. C. Spiegel","orcid":null,"position":8,"is_corresponding":false},{"id":291265,"name":"Lúcio Gama","orcid":"0000-0001-9511-012X","position":9,"is_corresponding":false},{"id":622895,"name":"Martin R. Gaudinski","orcid":"0000-0002-3743-5281","position":10,"is_corresponding":false},{"id":592583,"name":"E. Capparelli","orcid":null,"position":11,"is_corresponding":false},{"id":1444570,"name":"Dustin Huynh","orcid":"0000-0002-0514-0294","position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":null,"created_at":"2026-07-19T02:54:12.321988Z","pmid":"41549660","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":[]}