Haas D W, Clough L A, Johnson B W, Harris V L, Spearman P, Wilkinson G R, Fletcher C V, Fiscus S, Raffanti S, Donlon R, McKinsey J, Nicotera J, Schmidt D, Shoup R E, Kates R E, Lloyd R M, Larder B
Division of Infectious Diseases, Department of Medicine and Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37212, USA.
AIDS Res Hum Retroviruses. 2000 Oct 10;16(15):1491-502. doi: 10.1089/088922200750006010.
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(0-8hr) 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.
确定脑脊液（CSF）中HIV-1 RNA的来源将有助于开展脑部治疗效果的研究。4名未接受过抗逆转录病毒药物治疗的成年人接受了两次为期48小时的超密集脑脊液采样程序，一次在基线期，另一次在开始使用司他夫定、拉米夫定和奈非那韦进行三联药物治疗后的第4天开始。在基线期，通过每天向脑脊液中输入至少10⁴至10⁶个HIV-1 RNA拷贝来维持脑脊液中HIV-1 RNA浓度恒定。从基线期到第5天，脑脊液中HIV-1 RNA拷贝数/毫升的变化范围为-0.38至-1.18 log₁₀，血浆中为-0.80至-1.33 log₁₀，脑脊液和血浆变化之间无相关性。脑脊液或血浆中均未出现基因型或表型病毒耐药的证据。关于药代动力学，司他夫定的脑脊液与血浆曲线下面积（AUC）平均比值为38.9%，拉米夫定为15.3%。奈非那韦及其活性代谢产物M8在脑脊液中无法准确定量，尽管血浆中M8峰值水平和AUC(0-8小时)与脑脊液中HIV-1 RNA下降相关。本研究支持超密集脑脊液采样在研究中枢神经系统中HIV-1发病机制和治疗方面的实用性，并提供了强有力的证据表明脑脊液中的HIV-1 RNA至少部分来源于血浆以外的其他来源。
