PDF(Pubmed)
Abstract：
Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human immunodeficiency virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection from a fatal illness into a manageable chronic disorder. However, the presence of latent reservoirs, the multifaceted nature of HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict the efficacy of current cART targeting the distinct stages of the virus life cycle. Therefore, there is an unmet need for the discovery of new therapeutics that not only bypass the limitations of the current therapy but also protect the body\'s health at the same time. The main goal for complete HIV-1 eradication is purging latently infected cells from patients\' bodies. A potential strategy called \"lock-in and apoptosis\" targets the budding phase of the life cycle of the virus and leads to susceptibility to apoptosis of HIV-1 infected cells for the elimination of HIV-1 reservoirs and, ultimately, for complete eradication. The current work intends to present the main advantages and disadvantages of United States Food and Drug Administration (FDA)-approved anti-HIV-1 drugs as well as plausible strategies for the design and development of more anti-HIV-1 compounds with better potency, favorable pharmacokinetic profiles, and improved safety issues.
摘要：
获得性免疫缺陷综合征（AIDS）是人类免疫缺陷病毒（HIV-1）感染引起的巨大的全球健康威胁。到目前为止,抗逆转录病毒联合治疗(cART)的巨大进步已经将HIV-1感染从致命疾病转变为可控制的慢性疾病.然而,潜在水库的存在，艾滋病毒-1的多面性，耐药性，严重的脱靶效应，依从性差，和高成本限制了当前cART靶向病毒生命周期不同阶段的功效。因此,有一个未满足的需求，发现新的治疗方法，不仅绕过现有治疗的局限性，而且保护身体的健康，在同一时间。完全根除HIV-1的主要目标是从患者体内清除潜伏感染的细胞。一种称为“锁定和凋亡”的潜在策略针对病毒生命周期的萌芽阶段，并导致HIV-1感染细胞对细胞凋亡的敏感性，以消除HIV-1库，最终,彻底根除。目前的工作旨在介绍美国食品和药物管理局（FDA）批准的抗HIV-1药物的主要优点和缺点，以及设计和开发更多具有更好效力的抗HIV-1化合物的合理策略。有利的药代动力学特征，改善安全问题。
