Scott Yanille, Dezzutti Charlene S
University of Pittsburgh, Graduate School of Public Health, Pittsburgh, USA.
University of Pittsburgh, School of Medicine; Magee-Womens Research Institute. Pittsburgh, USA.
AIDS Rev. 2016 Jul-Sep;18(3):145-150.
Non-antiretroviral microbicide candidates were previously explored as a female-controlled method of preventing sexual transmission of HIV. These products contained non-HIV specific active compounds that were ultimately found to disrupt the vaginal epithelium, cause increased immune activation in the female genital tract, disturb vaginal flora, and/or cause other irritation that precluded their use as vaginal microbicides. Due to the failure of these first-generation candidates, there was a shift in focus to developing HIV pre-exposure prophylaxis and microbicides containing small-molecule antiretrovirals. Even with the limited success of the antiretroviral-based microbicides in clinical evaluations and no commercially available products, there has been significant progress in microbicide research. The lessons learned from previous trials have given rise to more rigorous preclinical evaluation that aims to be better at predicting microbicide efficacy and safety and to novel formulation and delivery technologies. These advances have resulted in renewed interest in developing non-antiretroviral-based microbicides, such as broadly neutralizing antibodies (for example, VRC01) and anti-viral proteins (for example, Griffithsin), as options for persons not wanting to use antiretroviral drugs, and for their potential to prevent multiple sexually transmitted infections.
非抗逆转录病毒杀微生物剂候选药物曾被探索作为一种由女性掌控的预防艾滋病毒性传播的方法。这些产品含有非艾滋病毒特异性活性化合物，最终发现它们会破坏阴道上皮，导致女性生殖道免疫激活增加，扰乱阴道菌群，和/或引起其他刺激，从而使其无法用作阴道杀微生物剂。由于这些第一代候选药物的失败，研究重点转向开发艾滋病毒暴露前预防药物和含有小分子抗逆转录病毒药物的杀微生物剂。尽管基于抗逆转录病毒的杀微生物剂在临床评估中取得的成功有限且尚无上市产品，但杀微生物剂研究仍取得了重大进展。从先前试验中吸取的经验教训催生了更严格的临床前评估，旨在更好地预测杀微生物剂的疗效和安全性，并催生了新型制剂和给药技术。这些进展使人们重新对开发基于非抗逆转录病毒的杀微生物剂产生兴趣，例如广泛中和抗体（例如，VRC01）和抗病毒蛋白（例如，格里菲斯素），它们可作为不愿使用抗逆转录病毒药物的人的选择，并且有可能预防多种性传播感染。
