Ene L, Duiculescu D, Ruta S M
Dr. Victor Babes Hospital for Infectious and Tropical Diseases, 281 Mihai Bravu Ave., District 3, 030303, Bucharest, Romania.
J Med Life. 2011 Nov 14;4(4):432-9. Epub 2011 Nov 24.
The central nervous system can act as a compartment in which HIV can replicate independently from plasma, and also as a sanctuary in which, under suboptimal drug pressure, HIV antiretroviral genetic variants can occur. Continuous replication of HIV in brain can contribute to neurocognitive impairment. Therefore, reaching adequate concentrations of antiretrovirals in the central nervous system might be essential in providing neuroprotection and improving neurocognition. Antiretrovirals have a restricted entry into the brain, due to several factors: the unique structure of the blood-brain barrier, and the existence of efficient efflux mechanisms. However, there is a high variability of antiretrovirals in reaching therapeutic drug concentrations in cerebrospinal fluid, that depend on the characteristics of the antiretrovirals (molecular weight, lipophilicity, protein binding) and on their capacity to be substrate for efflux transporters. The review aims to discuss the main mechanisms that interfere with antiretroviral penetration into central nervous system, and to summarize the current data concerning the penetrability of different antiretrovirals into the cerebrospinal fluid.
中枢神经系统可作为一个HIV能独立于血浆进行复制的隔室，也可作为一个庇护所，在药物压力欠佳的情况下，HIV抗逆转录病毒基因变异可能会在此出现。HIV在大脑中的持续复制会导致神经认知障碍。因此，在中枢神经系统中达到足够的抗逆转录病毒药物浓度对于提供神经保护和改善神经认知可能至关重要。由于多种因素，抗逆转录病毒药物进入大脑受到限制：血脑屏障的独特结构以及高效外排机制的存在。然而，抗逆转录病毒药物在脑脊液中达到治疗药物浓度的情况存在很大差异，这取决于抗逆转录病毒药物的特性（分子量、亲脂性、蛋白结合）及其作为外排转运体底物的能力。本综述旨在探讨干扰抗逆转录病毒药物进入中枢神经系统的主要机制，并总结有关不同抗逆转录病毒药物进入脑脊液渗透性的现有数据。
