Efficacy of cerebrospinal fluid (CSF)-penetrating antiretroviral drugs against HIV in the neurological compartment: Different patterns of phenotypic resistance in CSF and plasma
Efficacy of cerebrospinal fluid (CSF)-penetrating antiretroviral drugs against HIV in the neurological compartment: Different patterns of phenotypic resistance in CSF and plasma
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DOI：
10.1086/498310
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发表时间：
2005-12-15
影响因子：
11.8
通讯作者：
Piscitelli, SC
中科院分区：
文献类型：
--
作者：
Antinori, A;Perno, CF;Piscitelli, SC
背景资料。需要进一步研究人类免疫缺陷病毒(HIV)感染患者群体中多种药物的脑脊液浓度、HIV在血浆和脑脊液中的虚拟表型分布，以及这些表型与抗逆转录病毒治疗的相关性。同时测定了接受高效抗逆转录病毒治疗(HAART)的一大群HIV感染者的脑脊液和血浆中的药物浓度。样品的分析使用了一种有效的方法，该方法由液相色谱和质谱仪组成。对于病毒水平可检测到的患者，进行基因分型分析，然后进行虚拟表型研究。这项研究包括63名艾滋病毒感染患者，其中78%受到神经疾病的影响。脑脊液标本中未检测到地达诺辛、法韦仑、奈非那韦以及同时使用利托那韦和沙奎那韦的药物浓度。脑脊液浓度较高的是奈韦拉平，脑脊液与血浆浓度的中位数比为0.63，其次是拉米夫定(0.23)、司他夫定(0.20)和吲哚那韦(0.11)。在从脑脊液样本和血浆样本中获得病毒虚拟表型数据的40名患者中，有18名患者注意到至少有一种药物的脑脊液病毒和血浆病毒之间的耐药性倍数变化不同。与耐药倍数变化差异相关的因素是患者接触过的药物数量(P=.02)和是否存在神经疾病(P=.05)。治疗时间与脑脊液和血浆分离株的耐药性倍数变化之间存在显著的相关性。抗逆转录病毒药物在脑脊液中的渗透程度不同，有几种药物只能达到较低的脑脊液浓度。脑脊液分离株与血浆分离株具有不同的耐药性。对于疾病的脑脊液表现，有效的治疗决策可能需要更好地了解药物渗透和脑脊液中艾滋病毒的药物敏感性。
Background. Cerebrospinal fluid (CSF) concentrations of multiple drugs in a large human immunodeficiency virus (HIV)-infected patient population, the virtual phenotype profiles for HIV in the plasma and CSF compartments, and the correlation of these profiles with exposure to antiretroviral therapy need to be further investigated.Methods. Drug concentrations in CSF and plasma were concomitantly determined for a large group of HIV-infected individuals receiving highly active antiretroviral therapy (HAART). Samples were analyzed using a validated method consisting of liquid chromatography with mass spectrometry. For patients with detectable levels of virus, genotypic analysis was performed, followed by a virtual phenotype study.Results. Sixty-three HIV-infected patients were included in the study, 78% of whom were affected by neurological disease. Drug concentrations in CSF specimens were undetectable for didanosine, efavirenz, nelfinavir, and concomitantly administered ritonavir and saquinavir. CSF concentrations were higher for nevirapine, with a median CSF-to-plasma concentration ratio of 0.63, followed by lamivudine (0.23), stavudine (0.20), and indinavir (0.11). In 18 of the 40 patients with virtual phenotype data available for virus recovered from CSF samples and from plasma samples, differences in fold-change of resistance between the CSF virus and the plasma virus were noted for at least 1 drug. Factors associated with having differences in fold-change of resistance were number of drugs to which the patient had been exposed (P = .02) and presence of neurological disease (P = .05). A significant association was found between duration of therapy and fold-change of resistance in CSF and plasma isolates.Conclusions. Antiretrovirals have different levels of penetration in the CSF, with several drugs achieving only low CSF concentrations. CSF isolates have different resistance profiles than do plasma isolates. Effective treatment decisions for CSF manifestations of disease may require better knowledge of drug penetration and the drug susceptibility of HIV in the CSF.