Short communication - Enhancement of HIV infection by cellulose sulfate
Short communication - Enhancement of HIV infection by cellulose sulfate
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DOI：
10.1089/aid.2008.0043
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发表时间：
2008-07-01
影响因子：
1.5
通讯作者：
Hamer, Dean
中科院分区：
文献类型：
--
作者：
Tao, Wang;Richards, Chris;Hamer, Dean
纤维素硫酸盐是一种从棉花中提取的多阴离子化合物，已被建议作为一种局部杀菌剂来减少艾滋病毒的性传播。然而，在早期数据显示使用杀菌剂的女性比使用安慰剂的女性更高的艾滋病毒感染率后，硫酸纤维素阴道凝胶制剂(Ushercell)的第三阶段临床试验不得不提前关闭。硫酸纤维素试验的意想不到的结果促使我们重新检查并尝试复制该化合物和其他聚阴离子的现有临床前数据。我们在这里表明，在体外，纤维素硫酸盐对HIV感染有两个阶段的作用：在高浓度时，它抑制感染，但在低浓度时，它显着且可重复地增加HIV感染。这种刺激作用对致性传播的R5嗜性病毒株是明显的，反映的是感染率而不是病毒生长，并在临床相关的化合物浓度下发生。对已发表研究的审查表明，在独立实验室以前的研究中，纤维素硫酸盐的两相效应是明显的，对其他多阴离子，如糊精硫酸盐和PRO2000也发现了这种效应。这些数据有助于理解Ushercell临床试验的失败，并表明硫酸纤维素对人体粘膜应用是不安全的。
Cellulose sulfate, a polyanionic compound derived from cotton, has been proposed as a topical microbicide to reduce the sexual transmission of HIV. However, a phase III clinical trial of a vaginal gel formulation of cellulose sulfate (Ushercell) had to be prematurely closed after early data indicated microbicide users had a higher rate of HIV infection than women using a placebo. The unexpected results of the cellulose sulfate trail prompted us to reexamine and attempt to replicate the available preclinical data for this compound and other polyanions. We show here that cellulose sulfate has a biphasic effect on HIV infection in vitro: at high concentrations it inhibits infection but at low concentrations it significantly and reproducibly increases HIV infection. This stimulatory effect is evident for the R5-tropic strains of virus responsible for sexual transmission, reflects the rate of infection rather than viral growth, and occurs at clinically relevant concentrations of the compound. An examination of published studies shows that the biphasic effect of cellulose sulfate was evident in previous research by independent laboratories and is also found for other polyanions such as dextrin sulfate and PRO2000. These data help in understanding the failure of the Ushercell clinical trial and indicate that cellulose sulfate is not safe for mucosal application in humans.