Cerebrospinal fluid response to structured treatment interruption after virological failure
Cerebrospinal fluid response to structured treatment interruption after virological failure
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DOI：
10.1097/00002030-200107060-00006
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发表时间：
2001-07-06
期刊：
影响因子：
3.8
通讯作者：
Deeks, SG
中科院分区：
文献类型：
--
作者：
Price, RW;Paxinos, EE;Deeks, SG
目的结构化抗逆转录病毒治疗中断（STI）已被提倡作为HIV-1感染的治疗策略。我们报告了在病毒学失败后进行性传播感染期间进行连续腰椎穿刺（LPs）的5例患者脑脊液（CSF） HIV-1感染的初步观察。设计和方法在这项前瞻性观察性研究中，我们量化了HIV-1 RNA浓度，并评估了治疗中断期间脑脊液和血浆中表型药物敏感性谱和基因型抗病毒药物耐药性突变。同时计数脑脊液白细胞，监测患者神经系统状态。结果4例患者脑脊液HIV-1浓度升高速度快于血浆，导致血浆与脑脊液病毒载量之比（pVL:cVL）降低。3例患者出现无症状的脑脊液淋巴细胞增多症。在所有患者中，主要的HIV-1准种同时在脑脊液和血浆中从耐药表型转变为更敏感的表型，与耐药相关的基因型发生相同且同时的变化。结论STI可能伴随着先前未被认识到的组织病毒暴露和淋巴细胞流量的变化。因此，尽管持续的血浆病毒血症证明了“病毒学失败”，但在其中断之前持续的抗逆转录病毒治疗似乎抑制了CSF HIV-1感染（实际上比血浆更有效）并抑制了淋巴细胞进入CSF的运输。脑脊液和血浆中耐药突变的同时变化可能是由于预先存在的毒株的重新出现和过度生长，病毒在这两个区室之间随时交换，或促进或引发局部脑脊液淋巴细胞增多。(C) 2001 Lippincott Williams & Wilkins。
Objective Structured antiretroviral treatment interruption (STI) has been advocated as a therapeutic strategy for HIV-1 infection. We report initial observations of cerebrospinal fluid (CSF) HIV-1 infection in five patients undergoing serial lumbar punctures (LPs) during STI undertaken following virological failure.Design and methods In this prospective observational study we quantified HIV-1 RNA concentrations and assessed both phenotypic drug susceptibility profiles and genotypic antiviral drug resistance mutations in CSF and plasma during the period of treatment interruption. CSF white blood cells were also counted, and patients' neurological status monitored.Results In four of the patients, CSF HIV-1 concentration increased more rapidly than that of the plasma, with consequent reduction in the ratio between plasma and CSF viral loads (pVL :cVL). Three individuals developed robust, though asymptomatic CSF lymphocytic pleocytosis. In all patients the predominant HIV-1 quasispecies shifted simultaneously in CSF and plasma from a drug-resistant to a more drug-susceptible phenotype with identical and simultaneous changes in genotypes associated with drug resistance.Conclusions STI may be accompanied by previously unrecognized changes in tissue viral exposures and lymphocyte traffic. Hence, despite 'virological failure' as evidenced by persistent plasma viremia, ongoing antiretroviral treatment prior to its interruption appeared to suppress CSF HIV-1 infection (indeed more effectively than that of plasma) and restrain lymphocyte traffic into the CSF. Simultaneous change of resistance mutations in CSF and plasma was likely due to re-emergence and overgrowth of pre-existing strains with ready exchange of virus between these two compartments, either facilitated by or provoking a local CSF lymphocytosis. (C) 2001 Lippincott Williams & Wilkins.