{"doi":"10.1093/infdis/jiac041","title":"Safety and Pharmacokinetics of Monoclonal Antibodies VRC07-523LS and PGT121 Administered Subcutaneously for Human Immunodeficiency Virus Prevention","abstract":"BACKGROUND: Effective, long-acting prevention approaches are needed to reduce human immunodeficiency virus (HIV) incidence. We evaluated the safety and pharmacokinetics of VRC07-523LS and PGT121 administered subcutaneously alone and in combination as passive immunization for young women in South Africa. METHODS: CAPRISA 012A was a randomized, double-blinded, placebo-controlled, dose-escalation phase 1 trial. We enrolled 45 HIV-negative women into 9 groups and assessed safety, tolerability, pharmacokinetics, neutralization activity, and antidrug antibody levels. Pharmacokinetic modeling was conducted to predict steady-state concentrations for 12- and 24-weekly dosing intervals. RESULTS: VRC07-523LS and PGT121, administered subcutaneously, were safe and well tolerated. Most common reactogenicity events were injection site tenderness and headaches. Nine product-related adverse events were mild and transient. Median VRC07-523LS concentrations after 20 mg/kg doses were 9.65 μg/mL and 3.86 μg/mL at 16 and 24 weeks. The median week 8 concentration after the 10 mg/kg PGT121 dose was 8.26 μg/mL. Modeling of PGT121 at 20 mg/kg showed median concentrations of 1.37 μg/mL and 0.22 μg/mL at 16 and 24 weeks. Half-lives of VRC07-523LS and PGT121 were 29 and 20 days. Both antibodies retained neutralizing activity postadministration and no antidrug antibodies were detected. CONCLUSIONS: Subcutaneous administration of VRC07-523LS in combination with optimized versions of PGT121 or other antibodies should be further assessed for HIV prevention.","journal":"The Journal of Infectious Diseases","year":2022,"id":242772,"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":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":331062,"name":"Nigel Garrett","orcid":"0000-0002-4530-234X","position":1,"is_corresponding":false},{"id":330622,"name":"Edmund V. Capparelli","orcid":"0000-0002-1630-0505","position":2,"is_corresponding":false},{"id":386730,"name":"Farzana Osman","orcid":null,"position":3,"is_corresponding":false},{"id":874487,"name":"Ishana Harkoo","orcid":null,"position":4,"is_corresponding":false},{"id":463290,"name":"Nonhlanhla Yende‐Zuma","orcid":"0000-0002-3708-8611","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":596208,"name":"Natasha Samsunder","orcid":"0000-0003-3582-5718","position":8,"is_corresponding":false},{"id":536857,"name":"Cheryl Baxter","orcid":"0000-0002-6033-7655","position":9,"is_corresponding":false},{"id":355225,"name":"Nonhlanhla N. 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