Vaginal microbicides and the prevention of HIV transmission.
Vaginal microbicides and the prevention of HIV transmission.
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DOI：
10.1016/s1473-3099(08)70254-8
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发表时间：
2008-11
影响因子：
56.3
通讯作者：
Justman, Jessica
中科院分区：
文献类型：
--
作者：
Cutler, Blayne;Justman, Jessica
在全世界，艾滋病毒感染者中有近一半是妇女，她们主要通过异性性接触感染病毒。由于艾滋病毒疫苗可能需要数年时间，目前正在研究将阴道或直肠施用的局部杀微生物剂制剂作为预防艾滋病毒的另一种策略。一项关于预防阴道HIV传播的杀微生物剂开发的临床前和临床研究综述产生了118项研究：73项临床前研究和45项临床研究。临床前研究包括体外试验和宫颈外植体模型以及动物模型。临床研究包括I期和II/IIb期安全性研究以及III期疗效研究。尽管大多数I期和II期临床试验发现杀微生物剂化合物是安全的，耐受性良好，但迄今为止完成的III期试验尚未证明其在预防艾滋病毒传播方面的功效。局部杀微生物剂根据其破坏艾滋病毒性传播途径的位置分为五类。这些类别包括表面活性剂/膜破坏剂，阴道环境保护剂，病毒进入抑制剂，逆转录酶抑制剂，和第五组，其机制是未知的。杀微生物剂的发展轨迹一直朝着阻断更特异性的病毒-宿主细胞相互作用的药剂发展。杀微生物剂临床试验面临着科学和伦理上的复杂问题，例如安慰剂凝胶的选择，病毒耐药性的可能性，以及艾滋病毒感染者的参与。联合药物的评估将最有可能推进这一领域的研究。
Worldwide, nearly half of all individuals living with HIV are now women, who acquire the virus largely by heterosexual exposure. With an HIV vaccine likely to be years away, topical microbicide formulations applied vaginally or rectally are being investigated as another strategy for HIV prevention. A review of preclinical and clinical research on the development of microbicides formulated to prevent vaginal HIV transmission yielded 118 studies: 73 preclinical and 45 clinical. Preclinical research included in-vitro assays and cervical explant models, as well as animal models. Clinical research included phase I and II/IIb safety studies, and phase III efficacy studies. Whereas most phase I and phase II clinical trials have found microbicide compounds to be safe and well tolerated, phase III trials completed to date have not demonstrated efficacy in preventing HIV transmission. Topical microbicides are grouped into five classes of agents, based on where they disrupt the pathway of sexual transmission of HIV. These classes include surfactants/membrane disruptors, vaginal milieu protectors, viral entry inhibitors, reverse transcriptase inhibitors, and a fifth group whose mechanism is unknown. The trajectory of microbicide development has been toward agents that block more specific virus—host cell interactions. Microbicide clinical trials face scientifically and ethically complex issues, such as the choice of placebo gel, the potential for viral resistance, and the inclusion of HIV-infected participants. Assessment of combination agents will most likely advance this field of research.