دورية أكاديمية
Modeling cumulative overall prevention efficacy for the VRC01 phase 2b efficacy trials
| العنوان: | Modeling cumulative overall prevention efficacy for the VRC01 phase 2b efficacy trials |
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| المؤلفون: | Yunda Huang, Shelly Karuna, Lindsay N. Carpp, Daniel Reeves, Amarendra Pegu, Kelly Seaton, Kenneth Mayer, Joshua Schiffer, John Mascola, Peter B. Gilbert |
| المصدر: | Human Vaccines & Immunotherapeutics, Vol 14, Iss 9, Pp 2116-2127 (2018) |
| بيانات النشر: | Taylor & Francis Group, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Therapeutics. Pharmacology |
| مصطلحات موضوعية: | antibody mediated prevention trial, broadly neutralizing antibody, non-human primate challenge study, population pharmacokinetics, statistical modeling of hiv prevention efficacy, vrc01, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950 |
| الوصف: | The Antibody Mediated Prevention trials are assessing whether intravenously-administered VRC01 (10 mg/kg or 30 mg/kg vs placebo) can prevent HIV infection. In a modeling exercise, we used two models to predict the overall prevention efficacy (PE) of each VRC01 dose in preventing HIV infection. For the first per-exposure PE model, parameters were estimated from studies where nonhuman primates (NHPs) were administered high-dose intra-rectal simian-human immunodeficiency virus challenge two days post-VRC01 infusion at various dosages (“NHP model”). To account for the fact that humans may require greater VRC01 concentration to achieve the same level of protection, we next assumed that a 5-fold greater VRC01 serum concentration would be needed to provide the same level of per-exposure PE as seen in the NHP data (“5-fold model”). For the 10 mg/kg regimen, the 5-fold and NHP models predict an overall PE of 37% and 64%, respectively; for the 30 mg/kg regimen, the two models predict an overall PE of 53% and 82%, respectively. Our results support that VRC01 may plausibly confer positive PE in the AMP trials. Given the lack of available knowledge and data to verify the assumptions undergirding our modeling framework, its quantitative predictions of overall PE are preliminary. Its current main applications are to supplement decisions to advance mAb regimens to efficacy trials, and to enable mAb regimen ranking by their potential for PE in humans. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2164-5515 2164-554X 21645515 |
| Relation: | https://doaj.org/toc/2164-5515; https://doaj.org/toc/2164-554X |
| DOI: | 10.1080/21645515.2018.1462640 |
| URL الوصول: | https://doaj.org/article/14375d417ee24111baa289d8eaaa14dd |
| رقم الأكسشن: | edsdoj.14375d417ee24111baa289d8eaaa14dd |
| قاعدة البيانات: | Directory of Open Access Journals |
PDF full text from Publisher | تدمد: | 21645515 2164554X |
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| DOI: | 10.1080/21645515.2018.1462640 |