Science2014-06-11 5:35 PM

长效药物可保护机体免受SHIV感染 Long-Acting Integrase Inhibitor Protects Macaques from Intrarectal Simian/Human Immunodeficiency Virus

论文摘要 

一种现在正在进行临床试验的防止HIV感染的强效药物被重新配制成了一种长效的注射药物。Chasity Andrews及其同事证明,新的配方可保护猕猴不受反复的直肠内猴/人类免疫缺陷病毒(SHIV)的感染。该药的疗效和安全性还没有在人类中进行过测试。但是研究人员希望该长效药物在未来有可能被用于每月一次或每三个月一次的注射治疗,而这可帮助人们遵循他们的治疗方案。接触前预防(PrEP)治疗的临床试验是建立在给予那些没有感染HIV但却有感染高风险者的每日用药量的基础之上的。但要求人们每日坚持接受治疗却是困难的。在感染前一周给予猕猴这种GSK744 LA 的注射用药可保护所有的猕猴经受住因反复接触低剂量SHIV而被感染的考验。该药物的功效会随时间的推移而下降,因为其在体内的浓度会下降。但研究人员提示,每3个月给一次药可能会在人体内提供类似水平的对HIV的防护。

Abstract 

GSK1265744 (GSK744) is an integrase strand-transfer inhibitor that has been formulated as a long-acting (LA) injectable suitable for monthly to quarterly clinical administration. GSK744 LA was administered at two time points 4 weeks apart beginning 1 week before virus administration, and macaques were challenged weekly for 8 weeks. GSK744 LA, at plasma concentrations achievable with quarterly injections in humans, protected all animals against repeated low-dose challenges. In a second experiment, macaques were given GSK744 LA 1 week before virus administration and challenged repeatedly until infection occurred. Protection decreased over time and correlated with the plasma drug levels. With a quarterly dosing schedule in humans, our results suggest that GSK744 LA could potentially decrease adherence problems associated with daily preexposure prophylaxis (PrEP).

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