Calcagno Andrea, Di Perri Giovanni, Bonora Stefano
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, c/o Ospedale Amedeo di Savoia, C.so Svizzera 164, 10159, Torino, Italy,
Clin Pharmacokinet. 2014 Oct;53(10):891-906. doi: 10.1007/s40262-014-0171-0.
HIV-positive patients may be effectively treated with highly active antiretroviral therapy and such a strategy is associated with striking immune recovery and viral load reduction to very low levels. Despite undeniable results, the central nervous system (CNS) is commonly affected during the course of HIV infection, with neurocognitive disorders being as prevalent as 20-50 % of treated subjects. This review discusses the pathophysiology of CNS infection by HIV and the barriers to efficacious control of such a mechanism, including the available data on compartmental drug penetration and on pharmacokinetic/pharmacodynamic relationships. In the reviewed articles, a high variability in drug transfer to the CNS is highlighted with several mechanisms as well as methodological issues potentially influencing the observed results. Nevirapine and zidovudine showed the highest cerebrospinal fluid (CSF) to plasma ratios, although target concentrations are currently unknown for the CNS. The use of the composite CSF concentration effectiveness score has been associated with better virological outcomes (lower HIV RNA) but has been inconsistently associated with neurocognitive outcomes. These findings support the CNS effectiveness of commonly used highly antiretroviral therapies. The use of antiretroviral drugs with increased CSF penetration and/or effectiveness in treating or preventing neurocognitive disorders however needs to be assessed in well-designed prospective studies.
HIV阳性患者可通过高效抗逆转录病毒疗法得到有效治疗，这种治疗策略可使免疫系统显著恢复，并将病毒载量降至极低水平。尽管取得了不可否认的治疗效果，但在HIV感染过程中，中枢神经系统（CNS）通常会受到影响，神经认知障碍在接受治疗的患者中普遍存在，发生率为20%-50%。本综述讨论了HIV感染中枢神经系统的病理生理学以及有效控制这种机制的障碍，包括关于药物在脑内分布的穿透情况以及药代动力学/药效学关系的现有数据。在所综述的文章中，强调了药物向中枢神经系统转移的高度变异性，其中有几种机制以及方法学问题可能会影响观察结果。奈韦拉平和齐多夫定的脑脊液（CSF）与血浆比值最高，不过目前尚不清楚中枢神经系统的目标浓度。使用复合脑脊液浓度有效性评分与更好的病毒学结果（更低的HIV RNA水平）相关，但与神经认知结果的相关性并不一致。这些发现支持了常用高效抗逆转录病毒疗法对中枢神经系统的有效性。然而，需要在精心设计的前瞻性研究中评估使用脑脊液穿透性增加和/或对治疗或预防神经认知障碍有效的抗逆转录病毒药物的效果。
