Herrera Carolina, Shattock Robin J
Section of Infectious Diseases, Faculty of Medicine, St Mary's Campus, Imperial College, London, UK.
Curr HIV Res. 2012 Jan 1;10(1):42-52. doi: 10.2174/157016212799304607.
The new generation of microbicide candidates is based on the use of antiretroviral (ARV) drugs. The first compounds tested were selected among ARV classes that block the early stages of viral replication cycle, either entry/fusion or reverse transcription. Recently, an additional class of ARVs acting on a later step of viral replication has entered the microbicide pipeline, the protease inhibitors (PIs). This class of ARVs has shown strong potency in highly active antiretroviral therapy (HAART) against human immunodeficiency-1 virus (HIV-1) and lower levels of induced resistance compared to other ARV classes. As candidate microbicides, PIs will have to follow the guiding principles of microbicides being effective, safe, user-friendly and affordable. Hence, aspects including antiviral potency, adverse effects in mucosal tissues, formulation, pharmacology at mucosal sites, emergence of resistance, will have to be considered in the design of a PI-based microbicide. In addition, PIs will have to be tested for their capacity to be used in combination-based microbicides with other ARV classes and in combination with other preventive strategies, such as HIV-1 vaccines. Microbicides containing HIV PIs could also be potentially used against other pathologies specific to the female and/or male genital tract or colorectum.
新一代杀微生物剂候选药物基于抗逆转录病毒（ARV）药物的使用。最初测试的化合物是从阻断病毒复制周期早期阶段的ARV类别中挑选出来的，即进入/融合或逆转录阶段。最近，一类作用于病毒复制后期步骤的ARV，即蛋白酶抑制剂（PIs），也进入了杀微生物剂研发流程。这类ARV在高效抗逆转录病毒疗法（HAART）中对人类免疫缺陷病毒1型（HIV-1）显示出强大的效力，与其他ARV类别相比，诱导耐药性的水平较低。作为候选杀微生物剂，PIs必须遵循杀微生物剂有效、安全、用户友好且价格可承受的指导原则。因此，在设计基于PI的杀微生物剂时，必须考虑抗病毒效力、在粘膜组织中的不良反应、制剂、粘膜部位的药理学、耐药性的出现等方面。此外，还必须测试PIs与其他ARV类别联合使用以及与其他预防策略（如HIV-1疫苗）联合使用的能力。含有HIV PIs的杀微生物剂也可能潜在地用于对抗女性和/或男性生殖道或结肠直肠特有的其他疾病。
