Evidence of a source of HIV type 1 within the central nervous system by ultraintensive sampling of cerebrospinal fluid and plasma
Evidence of a source of HIV type 1 within the central nervous system by ultraintensive sampling of cerebrospinal fluid and plasma
复制标题
DOI：
10.1089/088922200750006010
复制
发表时间：
2000-10-01
影响因子：
1.5
通讯作者：
Larder, B
中科院分区：
文献类型：
--
作者：
Haas, DW;Clough, LA;Larder, B
确定脑脊液（CSF）中HIV-1 RNA的来源将有助于研究脑中的治疗效果。4名未接受过抗逆转录病毒药物治疗的成人接受了两次48小时超密集CSF采样程序，一次在基线，另一次在开始司他夫定、拉米夫定和奈非那韦三联疗法后第4天开始。基线时，通过每日至少10（4）至10（6）个HIV-1 RNA拷贝进入CSF，维持CSF HIV-1 RNA浓度恒定。从基线至第5天的变化范围为CSF中-0.38至-1.18 log（10）HIV-1 RNA拷贝/ml，血浆中-0.80至-1.33 log（10）HIV-1 RNA拷贝/ml，CSF和血浆变化之间无相关性。CSF或血浆中均无基因型或表型病毒耐药的证据。关于药代动力学，司他夫定和拉米夫定的平均CSF-血浆曲线下面积（AUC）比分别为38.9%和15.3%。尽管血浆M8峰水平和AUC（0-8）hr与CSF HIV-1 RNA下降相关，但无法准确定量CSF中的奈非那韦及其活性代谢产物M8。这项研究支持超密集CSF采样用于研究HIV-1在中枢神经系统中的发病机制和治疗，并提供了强有力的证据表明CSF中的HIV-1 RNA至少部分来自血浆以外的来源。
Defining the source of HIV-1 RNA in cerebrospinal fluid (CSF) will facilitate studies of treatment efficacy in the brain. Four antiretroviral drug-naive adults underwent two 48-hr ultraintensive CSF sampling procedures, once at baseline and again beginning on day 4 after initiating three-drug therapy with stavudine, lamivudine, and nelfinavir. At baseline, constant CSF HIV-1 RNA concentrations were maintained by daily entry of at least 10(4) to 10(6) HIV-1 RNA copies into CSF. Change from baseline to day 5 ranged from -0.38 to -1.18 log(10) HIV-1 RNA copies/ml in CSF, and from -0.80 to -1.33 log(10) HIV-1 RNA copies/ml in plasma, with no correlation between CSF and plasma changes. There was no evidence of genotypic or phenotypic viral resistance in either CSF or plasma. With regard to pharmacokinetics, mean CSF-to-plasma area-under-the-curve (AUC) ratios were 38.9% for stavudine and 15.3% for lamivudine. Nelfinavir and its active M8 metabolite could not be accurately quantified in CSF, although plasma M8 peak level and AUC(0-8) hr correlated with CSF HIV-1 RNA decline. This study supports the utility of ultraintensive CSF sampling for studying HIV-1 pathogenesis and therapy in the CNS, and provides strong evidence that HIV-1 RNA in CSF arises, at least in part, from a source other than plasma.