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首页> 外文期刊>Current medicinal chemistry. Anti-infective agents >Molecular basis of antiretroviral drugs-associated long-term toxicity:how bad can good drugs be?
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Molecular basis of antiretroviral drugs-associated long-term toxicity:how bad can good drugs be?

机译：抗逆转录病毒药物相关的长期毒性的分子基础：好的药物有多糟糕？

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Highly active antiretroviral therapy (HAART) has dramatically decreased the morbidity and mortality related with HIV-1 infection. However, at the same time, the impossibility of eradicating the infection has made lifelong therapy with antiretrovirals necessary. This has caused the emergence of multiple side effects, including previously unseen and unexpected adverse drug reactions. In addition, the combination of different classes of drugs sometimes sharing common toxic mechanisms has made additive toxicity an increasing event. The purpose of the present work is to review the molecular mechanisms of action of the different antiretrovirals now used in clinical practice, and through these to gain insight into the potential mechanisms of antiretroviral drugs-associated toxicity. Two basic mechanisms of toxicity have been described associated with antiretroviral drugs; i.e. mitochondrial toxicity associated with the use of nucleoside reverse transcriptase inhibitors (NRTIs), and the metabolic toxicities associated with HIV-1 protease inhibitors. Both types of mechanisms eventually cause multiple clinical manifestations, and among them, the most important are the fat redistribution syndromes associated with HIV-1 infection and HAART. On the other hand, the growing knowledge about the pathogenic mechanisms of antiretroviral drugs-associated toxicities has promoted advances in the therapeutic approach, and overall, the design of new and promising antiretroviral drugs that may avoid some of the prior deleterious consequences of antiretroviral drug administration. In the context of long-term antiretroviral treatment for long-term surviving HIV-1 infected patients, this may be the best hope for the still growing number of infected patients worldwide.
机译：高效的抗逆转录病毒疗法（HAART）大大降低了与HIV-1感染相关的发病率和死亡率。然而，与此同时，不可能消除感染已使抗逆转录病毒药物终身治疗成为必要。这引起了多种副作用的出现，包括以前看不见和意外的药物不良反应。此外，有时具有共同毒性机制的不同类别药物的组合使加成毒性日益增加。本工作的目的是回顾目前临床实践中使用的不同抗逆转录病毒药物的分子作用机理，并通过这些分子机理深入了解抗逆转录病毒药物相关毒性的潜在机制。已经描述了与抗逆转录病毒药物有关的两种基本的毒性机理;即与使用核苷逆转录酶抑制剂（NRTIs）相关的线粒体毒性，以及与HIV-1蛋白酶抑制剂相关的代谢毒性。两种机制最终都会导致多种临床表现，其中最重要的是与HIV-1感染和HAART相关的脂肪再分配综合征。另一方面，对抗逆转录病毒药物相关毒性的致病机理的认识不断提高，促进了治疗方法的发展，总体而言，新的有前途的抗逆转录病毒药物的设计可以避免先前抗逆转录病毒药物管理带来的有害后果。对于长期存活的HIV-1感染患者进行长期抗逆转录病毒治疗，对于全世界仍在不断增加的感染患者，这可能是最大的希望。

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