Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults.
Temporal Patterns and Drug Resistance in CSF Viral Escape Among ART-Experienced HIV-1 Infected Adults.
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DOI：
10.1097/qai.0000000000001362
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发表时间：
2017-06-01
期刊：
影响因子：
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通讯作者：
Gabuzda D
中科院分区：
文献类型：
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作者：
Mukerji SS;Misra V;Lorenz D;Cervantes-Arslanian AM;Lyons J;Chalkias S;Wurcel A;Burke D;Venna N;Morgello S;Koralnik IJ;Gabuzda D
补充数字内容可在正文中找到。在HIV-1感染的成年人中，脑脊液(CSF)病毒逃逸是一个日益被认识的临床事件。我们分析了纵向数据和耐药性突变，以描述接受抗逆转录病毒治疗的HIV-1感染患者的概况，这些患者的脑脊液和血浆中HIV-1RNA水平不一致。从2005年到2016年，从波士顿医院和国家神经艾滋病组织联盟(NNTC)发现了41例脑脊液逃逸病例，这些病例被定义为当血浆水平无法检测到时可检测到的脑脊液HIV-1 RNA，或者脑脊液中的HIV-1 RNA比血浆高0.5对数。据估计，波士顿和NNTC人群的脑脊液逃逸患病率分别为6.0%和6.8%；中位年龄为50岁，HIV-1感染持续时间为17年，CD4计数为329个/mm3，CD4最低值为21个/mm3。30例有神经系统症状，4例有反复脑脊液逃逸。根据过去24个月的血浆HIV-1RNA水平将病例分为三个亚型：高度病毒血症(1000拷贝/毫升)、低度病毒血症(LLV：51-999拷贝/毫升)和血浆抑制伴脑脊液闪光或逃逸(CSFRNA和≥200拷贝/毫升)。高度病毒血症患者报告更多的药物滥用，而LLV或血浆抑制患者更有神经症状(81%对53%)；75%的重复脑脊液逃逸病例被归类为LLV。当血浆≤水平为每毫升50个拷贝时，74%的脑脊液样本中发现M184V/I突变。在脑脊液逃逸中经常观察到的特征包括HIV-1感染和15年，既往LLV，以及脑脊液中M184V/I突变。基于先前血浆HIV RNA水平的分类为确定病因和测试治疗方法提供了有用的概念框架。
Supplemental Digital Content is Available in the Text. Cerebrospinal fluid (CSF) viral escape is an increasingly recognized clinical event among HIV-1-infected adults. We analyzed longitudinal data and drug-resistance mutations to characterize profiles of HIV-1-infected patients on antiretroviral therapy with discordant CSF and plasma HIV-1 RNA levels. Forty-one cases of CSF escape defined as detectable CSF HIV-1 RNA when plasma levels were undetectable, or HIV-1 RNA >0.5-log higher in CSF than plasma were identified from Boston Hospitals and National NeuroAIDS Tissue Consortium (NNTC) from 2005 to 2016. Estimated prevalence of CSF escape in Boston and NNTC cohorts was 6.0% and 6.8%, respectively; median age was 50, duration of HIV-1 infection 17 years, CD4 count 329 cells/mm3 and CD4 nadir 21 cells/mm3. Neurological symptoms were present in 30 cases; 4 had repeat episodes of CSF escape. Cases were classified into subtypes based plasma HIV-1 RNA levels in the preceding 24 months: high-level viremia (1000 copies/mL), low-level viremia (LLV: 51–999 copies/mL), and plasma suppression with CSF blip or escape (CSF RNA <200 or ≥200 copies/mL). High-level viremia cases reported more substance abuse, whereas LLV or plasma suppression cases were more neurosymptomatic (81% vs. 53%); 75% of repeat CSF escape cases were classified LLV. M184V/I mutations were identified in 74% of CSF samples when plasma levels were ≤50 copies per milliliter. Characteristics frequently observed in CSF escape include HIV-1 infection >15 years, previous LLV, and M184V/I mutations in CSF. Classification based on preceding plasma HIV RNA levels provides a useful conceptual framework to identify causal factors and test therapeutics.