Gaikwad Shraddha Y, Phatak Pallavi, Mukherjee Anupam
Division of Virology, ICMR-National AIDS Research Institute, Pune, MH, India.
Heliyon. 2023 May 5;9(5):e16027. doi: 10.1016/j.heliyon.2023.e16027. eCollection 2023 May.
The advent of Highly Active Antiretroviral Therapy has majorly contributed towards reducing the morbidity and mortality associated with HIV infected people, thus improving the quality of their life. Still, the eradication of HIV infection has not been achieved due to some important limitations such as non-adherence to therapy, cellular toxicity, restricted bioavailability of antiretroviral drugs and emergence of drug resistant viruses. Moreover, persistence of latent HIV-reservoirs even under antiviral-drug pressure is the major obstacle in HIV cure. Currently used antiretrovirals can suppress the viral replication in activated CD4 cells, however, it has been observed that the available antiretroviral therapy appears inadequate to reduce latent reservoirs established in resting memory CD4 T cells. Therefore, for eradication or reduction of latent reservoirs many immunotherapeutic and pharmacologic approaches including latency reversing agents are being studied constantly. Additionally, promising therapeutic strategies including discovery of novel drugs and drug targets are continuously being explored. Therefore, preclinical testing has become an important step of drug development process, continuously demanding innovative, but less time consuming evaluation strategies. Present review attempts to gather and line-up the information on existing cell-based methodologies applied for assessing drug candidates for their antiretroviral potential. Further, we intend to outline the advanced and reliable cell based methodologies that would expedite the process of discovery and development of antiretrovirals.
高效抗逆转录病毒疗法的出现极大地有助于降低与艾滋病毒感染者相关的发病率和死亡率，从而改善他们的生活质量。然而，由于一些重要的局限性，如不坚持治疗、细胞毒性、抗逆转录病毒药物的生物利用度受限以及耐药病毒的出现，艾滋病毒感染尚未得到根除。此外，即使在抗病毒药物压力下，潜伏性艾滋病毒储存库的持续存在也是治愈艾滋病毒的主要障碍。目前使用的抗逆转录病毒药物可以抑制活化的CD4细胞中的病毒复制，然而，据观察，现有的抗逆转录病毒疗法似乎不足以减少在静息记忆CD4 T细胞中建立的潜伏储存库。因此，为了根除或减少潜伏储存库，包括潜伏期逆转剂在内的许多免疫治疗和药理学方法正在不断研究。此外，包括发现新药和药物靶点在内的有前景的治疗策略也在不断探索。因此，临床前测试已成为药物开发过程中的一个重要步骤，不断需要创新但耗时较少的评估策略。本综述试图收集并整理有关用于评估候选药物抗逆转录病毒潜力的现有基于细胞的方法的信息。此外，我们打算概述先进且可靠的基于细胞的方法，这些方法将加快抗逆转录病毒药物的发现和开发过程。
