Cabotegravir long acting injection protects macaques against intravenous challenge with SIVmac251
Cabotegravir long acting injection protects macaques against intravenous challenge with SIVmac251
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DOI：
10.1097/qad.0000000000001343
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发表时间：
2017-02-20
期刊：
影响因子：
3.8
通讯作者：
Markowitz, Martin
中科院分区：
文献类型：
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作者：
Andrews, Chasity D.;Bernard, Leslie St.;Markowitz, Martin
目的：我们评估了cabotegravir（CAB; GSK 1265744或GSK 744）在基于每行为感染概率模拟输血的模型中长期充当针对静脉内猿猴免疫缺陷病毒（SIV）攻击的暴露前预防（PrEP）。设计：CAB长效是一种整合酶链转移抑制剂，配制为200 mg/ml可注射的纳米颗粒悬浮液，其是针对猕猴中的直肠和阴道猿猴/人类免疫缺陷病毒传播的有效PrEP剂。三组恒河猴（每组n = 8）肌肉内注射CAB长效剂，并在第2周静脉内用17只动物感染剂量的50%SIVmac 251攻击。第1组在第0周和第4周注射50 mg/kg，以评价模拟性传播的猕猴研究中使用的CAB长效剂量的保护效力。第2组在第0周注射50 mg/kg CAB，以评估第二次注射CAB长效保护对抗静脉内攻击的必要性。第3组在第0周注射25 mg/kg，第4周注射50 mg/kg，以将攻击时的CAB血浆浓度与保护作用相关联。五个额外的猕猴仍然未经处理的controls.Results：CAB长效是高度保护与21的24 CAB long-actingtreated猕猴剩余aviremic，导致88%的保护。血浆CAB浓度在病毒的挑战时间似乎是更重要的保护比维持治疗血浆浓度与第二CAB长效injection.Conclusion：这些结果支持CAB长期充当PrEP在注射药物的人的临床调查。版权所有（C）2017威科医疗集团All rights reserved.
Objective: We evaluated the effectiveness of cabotegravir (CAB; GSK1265744 or GSK744) long acting as preexposure prophylaxis (PrEP) against intravenous simian immunodeficiency virus (SIV) challenge in a model that mimics blood transfusions based on the per-act probability of infection.Design: CAB long acting is an integrase strand transfer inhibitor formulated as a 200 mg/ml injectable nanoparticle suspension that is an effective PrEP agent against rectal and vaginal simian/human immunodeficiency virus transmission in macaques.Methods: Three groups of rhesus macaques (n = 8 per group) were injected intramus-cularly with CAB long acting and challenged intravenously with 17 animal infectious dose 50% SIVmac251 on week 2. Group 1 was injected with 50 mg/kg on week 0 and 4 to evaluate the protective efficacy of the CAB long-acting dose used in macaque studies mimicking sexual transmission. Group 2 was injected with 50 mg/kg on week 0 to evaluate the necessity of the second injection of CAB long acting for protection against intravenous challenge. Group 3 was injected with 25 mg/kg on week 0 and 50 mg/kg on week 4 to correlate CAB plasma concentrations at the time of challenge with protection. Five additional macaques remained untreated as controls.Results: CAB long acting was highly protective with 21 of the 24 CAB long-actingtreated macaques remaining aviremic, resulting in 88% protection. The plasma CAB concentration at the time of virus challenge appeared to be more important for protection than sustaining therapeutic plasma concentrations with the second CAB long acting injection.Conclusion: These results support the clinical investigation of CAB long acting as PrEP in people who inject drugs. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.