Andrews Chasity D, Bernard Leslie St, Poon Amanda Yee, Mohri Hiroshi, Gettie Natanya, Spreen William R, Gettie Agegnehu, Russell-Lodrigue Kasi, Blanchard James, Hong Zhi, Ho David D, Markowitz Martin
aAaron Diamond AIDS Research Center, The Rockefeller University, New York City, New York bViiV Healthcare, Research Triangle Park, North Carolina cTulane National Primate Research Center, Covington, Louisiana dGlaxoSmithKline, Research Triangle Park, North Carolina, USA.
AIDS. 2017 Feb 20;31(4):461-467. doi: 10.1097/QAD.0000000000001343.
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.
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.
Three groups of rhesus macaques (n = 8 per group) were injected intramuscularly 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.
CAB long acting was highly protective with 21 of the 24 CAB long-acting-treated 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.
These results support the clinical investigation of CAB long acting as PrEP in people who inject drugs.
在一个基于每次感染概率模拟输血的模型中，我们评估了长效卡博特韦（CAB；GSK1265744或GSK744）作为暴露前预防（PrEP）预防静脉注射猴免疫缺陷病毒（SIV）攻击的有效性。
长效CAB是一种整合酶链转移抑制剂，配制成200mg/ml的可注射纳米颗粒悬浮液，是一种有效的PrEP药物，可预防猕猴直肠和阴道猴/人免疫缺陷病毒传播。
三组恒河猴（每组n = 8只）在第2周接受长效CAB肌肉注射，并静脉注射17个动物感染剂量50%的SIVmac251进行攻击。第1组在第0周和第4周注射50mg/kg，以评估在模拟性传播的猕猴研究中使用的长效CAB剂量的保护效果。第2组在第0周注射50mg/kg，以评估第二次注射长效CAB对预防静脉攻击的必要性。第3组在第0周注射25mg/kg，在第4周注射50mg/kg，以将攻击时的CAB血浆浓度与保护作用相关联。另外5只猕猴未接受治疗作为对照。
长效CAB具有高度保护作用，24只接受长效CAB治疗的猕猴中有21只保持无病毒血症，保护率达88%。病毒攻击时的血浆CAB浓度似乎比第二次注射长效CAB维持治疗性血浆浓度对保护作用更重要。
这些结果支持对长效CAB作为注射吸毒者PrEP进行临床研究。
