Department of Pharmacology, Maulana Azad Medical College, New Delhi, India.
Expert Opin Pharmacother. 2011 Jan;12(1):31-46. doi: 10.1517/14656566.2010.509345. Epub 2010 Aug 10.
Acquired immunodeficiency syndrome (AIDS) is one of the leading causes of death worldwide. Although the combination therapies of highly active antiretroviral therapy (HAART) have significantly contributed to virological suppression, improved immune function and quality of life, issues such as tolerability, drug-drug interactions and cross-resistance amongst members of a particular drug class still pose a significant barrier to long-term successful treatment. There is a constant need for newer anti HIV drugs with increased potency and improved pharmacokinetic properties either in the existing classes or drugs from new classes that target several new steps in HIV replication cycle.
The authors have discussed newer antiretroviral drugs belonging to second-generation nucleoside analog reverse transcriptase inhibitors (amdoxovir, elvucitabine, apricitabine, racivir), non-nucleoside analog reverse transcriptase inhibitors (etravirine, rilpivirine), protease inhibitors (darunavir, tipranavir) as well as emerging new classes, i.e., fusion inhibitors (enfuvirtide, sifuvirtide), CCR5 inhibitors (maraviroc, vicriviroc, PRO 140, PRO 542), CD4-receptor inhibitors (ibalizumab), integrase inhibitors (raltegravir, elvitegravir, GSK-1349572), maturation inhibitors (bevirimat), cobicistat (pharmacoenhancer), lens epithelium-derived growth factor inhibitors and capsid assembly inhibitors.
The reader will gain an understanding of the mechanism of action, mechanism of resistance, stages of development and important clinical trials related to the newer antiretroviral drugs and future potential of these drugs.
The initial clinical trial data of these newer drugs are very encouraging for the long-term successful control of HIV in both treatment-naïve and treatment-experienced patients.
艾滋病(AIDS)是世界范围内导致死亡的主要原因之一。尽管高效抗逆转录病毒疗法(HAART)的联合治疗方案极大地促进了病毒学抑制、免疫功能改善和生活质量提高,但在特定药物类别成员之间的耐受性、药物相互作用和交叉耐药等问题仍然是长期成功治疗的重大障碍。人们一直需要具有更高效力和改善药代动力学特性的新型抗 HIV 药物,这些药物可以是现有类别中的新药,也可以是针对 HIV 复制周期中几个新步骤的新型类别药物。
作者讨论了属于第二代核苷类似物逆转录酶抑制剂(amdoxovir、elvucitabine、apricitabine、racivir)、非核苷类似物逆转录酶抑制剂(etravirine、rilpivirine)、蛋白酶抑制剂(darunavir、tipranavir)以及新兴的新型类别药物,如融合抑制剂(enfuvirtide、sifuvirtide)、CCR5 抑制剂(maraviroc、vicriviroc、PRO 140、PRO 542)、CD4 受体抑制剂(ibalizumab)、整合酶抑制剂(raltegravir、elvitegravir、GSK-1349572)、成熟抑制剂(bevirimat)、cobicistat(药效增强剂)、晶状体上皮衍生生长因子抑制剂和衣壳装配抑制剂的新型抗逆转录病毒药物。
读者将了解新型抗逆转录病毒药物的作用机制、耐药机制、研发阶段以及与这些药物相关的重要临床试验和未来潜力。
这些新型药物的初步临床试验数据非常令人鼓舞,它们有望在治疗初治和治疗经验丰富的患者中实现 HIV 的长期成功控制。