Long-acting integrase inhibitor protects macaques from intrarectal simian/human immunodeficiency virus.
Long-acting integrase inhibitor protects macaques from intrarectal simian/human immunodeficiency virus.
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DOI：
10.1126/science.1248707
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发表时间：
2014-03-07
期刊：
影响因子：
--
通讯作者：
Ho DD
中科院分区：
文献类型：
--
作者：
Andrews CD;Spreen WR;Mohri H;Moss L;Ford S;Gettie A;Russell-Lodrigue K;Bohm RP;Cheng-Mayer C;Hong Z;Markowitz M;Ho DD
GSK1265744（GSK744）是一种整合酶链转移抑制剂，已被配制为长效（LA）注射剂，适用于每月至每季度的临床给药。在病毒施用前1周开始，在间隔4周的两个时间点施用GSK 744 LA，并且每周攻击猕猴，持续8周。GSK744 LA在人体中每季度注射一次可达到的血浆浓度下，可保护所有动物免受重复低剂量攻击。在第二个实验中，在病毒给药前1周给予猕猴GSK744 LA，并反复激发直至发生感染。保护作用随时间降低，并与血浆药物水平相关。在人类中采用季度给药计划，我们的研究结果表明，GSK744 LA可能会减少与每日暴露前预防（PrEP）相关的依从性问题。
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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