Antiviral Pharmacology Laboratory, University of Nebraska Medical Center, College of Pharmacy, Omaha, NE 68198, USA.
Curr Opin HIV AIDS. 2013 May;8(3):190-5. doi: 10.1097/COH.0b013e32835fc68a.
Current antiretroviral treatment regimens represent significant improvements in the management of HIV-1 infection; however, these regimens have not achieved a functional or sterilizing cure. One barrier to achieving a cure may be suboptimal antiretroviral concentrations in sanctuary sites throughout the body, including the central nervous system, gut-associated lymphoid tissue, lymph nodes, and tissue macrophages. This review will focus on the problems associated with achieving effective concentrations in these restricted sanctuary sites, and potential strategies to overcome these barriers.
Sufficient data exist to conclude that antiretroviral drug distribution is not uniform throughout the body. Low tissue/reservoir concentrations may be associated with viral replication. Multiple means to increase drug concentrations in sanctuary sites are being investigated, including modification of currently utilized drugs, blockade of transporters and enzymes that affect drug metabolism and pharmacokinetics, and local drug administration. Accumulating data suggest these methods increase antiretroviral concentrations in reservoirs of viral replication. No method has yet resulted in the complete clearance of HIV.
New strategies for increasing antiretroviral concentrations in predominant sites of viral replication may provide more effective means for elimination of viral sanctuaries. Additional research is necessary to optimize antiretroviral tissue distribution in order to inhibit virus replication fully, and avoid resistance and replenishment of viral reservoirs that may persist in the face of antiretroviral therapy.
目前的抗逆转录病毒治疗方案代表了 HIV-1 感染管理的重大进展；然而，这些方案并未实现功能性或杀菌性治愈。实现治愈的一个障碍可能是全身避难所部位（包括中枢神经系统、肠道相关淋巴组织、淋巴结和组织巨噬细胞）的抗逆转录病毒浓度不理想。这篇综述将重点讨论在这些受限的避难所部位实现有效浓度的问题，以及克服这些障碍的潜在策略。
有足够的数据得出结论，抗逆转录病毒药物在全身的分布并不均匀。组织/储存浓度低可能与病毒复制有关。正在研究多种增加避难所部位药物浓度的方法，包括对现有药物进行修饰、阻断影响药物代谢和药代动力学的转运体和酶，以及局部给药。越来越多的数据表明，这些方法增加了病毒复制的储库中的抗逆转录病毒浓度。目前还没有一种方法能完全清除 HIV。
增加主要病毒复制部位抗逆转录病毒浓度的新策略可能为消除病毒避难所提供更有效的方法。为了完全抑制病毒复制，避免耐药性和可能在抗逆转录病毒治疗下持续存在的病毒储存库的补充，有必要进一步研究优化抗逆转录病毒的组织分布。
