{"doi":"10.1093/jac/dkaf181","title":"Population pharmacokinetics of weight-based compared with fixed dosing of CAP256V2LS, a broadly neutralizing antibody for HIV prevention in women","abstract":"INTRODUCTION: In the development of broadly neutralizing monoclonal antibodies (bNAb) for HIV prevention, there is a need for simpler dosing strategies. This study assessed whether fixed dosing achieves comparable systemic bNAb concentrations to weight-based dosing across a range of weights. METHODS: The CAPRISA 012B trial was a first-in-human, Phase 1 dose-escalation study conducted in young, HIV-negative women (median age 25 years; IQR: 22-29) in South Africa, evaluating the subcutaneous administration of CAP256V2LS alone and in combination with VRC07-523LS. Weight-based dosing between 5 and 20 mg/kg was assessed. A fixed 1200 mg dose of CAP256V2LS and VRC07-523LS, administered alone or in combination, was evaluated in women weighing from 59.5 kg to 93.2 kg, with a median weight of 78.3 kg (IQR: 67.2-81.5). A population pharmacokinetic model was developed to describe and predict the concentration-time profiles of CAP256V2LS in participants. Model-based simulations then extended this analysis across a broader hypothetical weight range (34.2-119 kg). RESULTS: Model-based simulations revealed comparable exposure between the 1200 mg fixed-dose and the 20 mg/kg weight-based dosing regimens. Inter-individual variability in bioavailability and clearance was 0.212 and 0.019, respectively, and was consistent across both fixed-dose and weight-based dosing, regardless of the route of administration. Weight-based dosing of CAP256V2LS led to a mean wastage of 265.8 mg for the 5 mg/kg dose, 433.4 mg for the 10 mg/kg dose, and 324.2 mg for the 20 mg/kg dose. CONCLUSIONS: For women weighing 60-93 kg, a fixed-dose of 1200 mg of CAP256V2LS produced similar adverse events and pharmacokinetic profiles as weight-based dosing. The fixed dose reduced variability in the plasma concentrations and product wastage compared with weight-based dosing.","journal":"Journal of Antimicrobial Chemotherapy","year":2025,"id":544556,"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":0.9426,"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":905650,"name":"Martin Béliveau","orcid":null,"position":1,"is_corresponding":false},{"id":1435089,"name":"Roberto Heredia‐Ortiz","orcid":null,"position":2,"is_corresponding":false},{"id":386730,"name":"Farzana Osman","orcid":null,"position":3,"is_corresponding":false},{"id":1305381,"name":"Marothi Letsoalo","orcid":null,"position":4,"is_corresponding":false},{"id":331062,"name":"Nigel Garrett","orcid":"0000-0002-4530-234X","position":5,"is_corresponding":false},{"id":596207,"name":"Tanuja N. Gengiah","orcid":"0000-0002-3405-5128","position":6,"is_corresponding":false},{"id":434270,"name":"Derseree Archary","orcid":"0000-0002-2216-2866","position":7,"is_corresponding":false},{"id":104332,"name":"Jennifer Wang","orcid":"0000-0002-2556-9100","position":8,"is_corresponding":false},{"id":480600,"name":"Sandeep Narpala","orcid":"0000-0002-1447-2709","position":9,"is_corresponding":false},{"id":847577,"name":"Mike Castro","orcid":"0000-0002-8045-1754","position":10,"is_corresponding":false},{"id":846676,"name":"Leonid Serebryannyy","orcid":"0000-0003-0213-1779","position":11,"is_corresponding":false},{"id":324820,"name":"Kevin Carlton","orcid":null,"position":12,"is_corresponding":false},{"id":290824,"name":"Richard A. Koup","orcid":"0000-0002-3090-7282","position":13,"is_corresponding":false},{"id":138629,"name":"Penny L. Moore","orcid":"0000-0001-8719-4028","position":14,"is_corresponding":false},{"id":36867,"name":"Lynn Morris","orcid":"0000-0003-3961-7828","position":15,"is_corresponding":false},{"id":385889,"name":"Quarraisha Abdool Karim","orcid":"0000-0002-0985-477X","position":16,"is_corresponding":false},{"id":385888,"name":"Salim S. Abdool Karim","orcid":"0000-0002-4986-2133","position":17,"is_corresponding":false},{"id":1364998,"name":"Sharana Mahomed","orcid":"0009-0005-1449-160X","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T02:53:12.864581Z","pmid":"40458046","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":[]}