Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system
Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system
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DOI：
10.1001/archneurol.2007.31
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发表时间：
2008-01-01
影响因子：
--
通讯作者：
Ellis, Ronald J.
中科院分区：
文献类型：
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作者：
Letendre, Scott;Marquie-Beck, Jennifer;Ellis, Ronald J.
目的：为了评估是否渗透到中枢神经系统（CNS）的组合方案，估计由CNS渗透有效性（CPE）秩，与较低的脑脊液（CSF）viral load.Design：数据进行了分析，从467名参与者谁是人类免疫缺陷病毒（HIV）血清阳性，谁报告抗逆转录病毒（ARV）药物的使用。在临床研究中，根据其化学性质、CSF中的浓度和/或CNS中的有效性，将单个ARV药物的渗透等级指定为0（低）、0.5（中等）或1（高）。CPE等级通过将每个ARV在该方案中的个体渗透等级相加来计算。结果：CPE等级的中位数为1.5（四分位数间距，1-2）。较低的CPE等级与较高的CSF病毒载量相关。排名小于2与可检测到CSF病毒载量的几率增加88%相关。在多变量回归分析中，较低的CPE等级与可检测的CSF病毒载量相关，即使在调整了ARV药物的总数，ARV药物依从性，血浆病毒载量，持续时间和类型的当前方案，和CD 4 counter.Conclusions：Poplantation的ARV药物渗透到中枢神经系统似乎允许继续在中枢神经系统中复制的HIV病毒载量较高。由于抑制HIV在CNS中的复制可能是治疗HIV相关神经认知障碍患者的关键，因此应在共识治疗指南中考虑解释CNS渗透的ARV治疗策略，并在临床研究中进行验证。
Objective: To evaluate whether penetration of a combination regimen into the central nervous system (CNS); as estimated by the CNS Penetration-Effectiveness (CPE) rank, is associated with lower cerebrospinal fluid (CSF) viral load.Design: Data were analyzed from 467 participants who were human immunodeficiency virus (HIV) seropositive and who reported antiretroviral (ARV) drug use. Individual ARV drugs were assigned a penetration rank of 0 (low), 0.5 (intermediate), or 1 (high) based on their chemical properties, concentrations in CSF, and/or effectiveness in the CNS in clinical studies. The CPE rank was calculated by summing the individual penetration ranks for each ARV in the regimen.Results: The median CPE rank was 1.5 (interquartile range, 1-2). Lower CPE ranks correlated with higher CSF viral loads. Ranks less than 2 were associated with an 88% increase in the odds of detectable CSF viral load. In multivariate regression, lower CPE ranks were associated with detectable CSF viral loads even after adjusting for total number of ARV drugs, ARV drug adherence, plasma viral load, duration and type of the current regimen, and CD4 count.Conclusions: Poorer penetration of ARV drugs into the CNS appears to allow continued HIV replication in the CNS as indicated by higher CSF HIV viral loads. Because inhibition of HIV replication in the CNS is probably critical in treating patients who have HIV-associated neurocognitive disorders, ARV treatment strategies that account for CNS penetration should be considered in consensus treatment guidelines and validated in clinical studies.