HIV-1 resistant strains acquired at the time of primary infection massively fuel the cellular reservoir and persist for lengthy periods of time
HIV-1 resistant strains acquired at the time of primary infection massively fuel the cellular reservoir and persist for lengthy periods of time
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DOI：
10.1097/01.aids.0000199820.47703.a0
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发表时间：
2006-01-09
期刊：
影响因子：
3.8
通讯作者：
Chaix, ML
中科院分区：
文献类型：
--
作者：
Ghosn, J;Pellegrin, I;Chaix, ML
目的：在原发性HIV-1感染（PHI）时获得耐药株的患者中病毒储库的早期建立的表征，以及循环病毒体和细胞内HIV株中耐药突变的纵向分析。比较HIV RNA和外周血单个核细胞（PBMC）的耐药性。入组Primo队列的44例患者在发生PHI时的HIV DNA，这些患者的血浆HIV-1对至少一种抗逆转录病毒药物耐药。在10例患者的亚组中，对血浆HIV RNA和PBMC HIV DNA中的病毒载量和耐药基因型进行了至少24个月的纵向监测。结果：44例患者的基线耐药谱在配对HIV RNA和PBMC HIV DNA中均一致。在5名未经治疗的患者中，所有耐药相关突变在血浆和PBMC中持续2年以上。在开始经验性HAART治疗的5名患者中，2名患者在第6个月时检测不到HIV RNA，PBMC HIV DNA中长期存在存档的耐药突变。在其他三名患者中观察到病毒学失败，导致其中两名患者在HIV RNA和HIV DNA中积累了额外的耐药性突变。HIV DNA克隆的系统发育分析显示，在基线时，在细胞库中存在高度同质和完全耐药的准种。结论：在PHI时获得的HIV耐药株大量地为细胞库提供燃料，并且它们的长期持久性是由占主导地位的同质和耐药病毒群体的早期扩张所支持的。治疗患者的结果表明，经典的经验性三联疗法可能是次优的。(C)2006年利平科特威廉姆斯&威尔金斯。
Objective: Characterization of the early establishment of the viral reservoir in patients acquiring resistant strains at primary HIV-1 infection (PHI), and longitudinal analysis of resistance mutations in circulating virions and intracellular HIV strains.Patients and methods: Drug-resistance was compared between HIV RNA and peripheral blood mononuclear cell (PBMC)-HIV DNA at the time of PHI in 44 patients enrolled in the Primo Cohort and harbouring plasma HIV-1 resistant to at least one antiretroviral drug. Longitudinal monitoring of viral load and resistance genotype was performed in plasma-HIV RNA and PBMC HIV DNA for at least 24 months in a subset of 10 patients. Phylogenetic analysis of HIV DNA protease gene clones was used to explore the diversity of quasi-species at baseline.Results: Baseline resistance profile was identical in paired HIV RNA and PBMC HIV DNA for all 44 patients. All resistance-associated mutations persisted in plasma and PBMC over 2 years in the five untreated patients. Of the five patients started on empirical HAART, two achieved undetectable HIV RNA at month 6, with long-term persistence of archived drug-resistance mutations in PBMC HIV DNA. Virological failure was observed in the other three patients, resulting in the accumulation of additional drug-resistance mutations in HIV RNA and HIV DNA for two of them. Phylogenetic analysis of HIV DNA clones showed highly homogenous and exclusively resistant quasi-species in the cellular reservoir at baseline.Conclusion: HIV resistant strains acquired at the time of PHI massively fuel the cellular reservoir, and their prolonged persistence is supported by the early expansion of a dominant homogenous and resistant viral Population. Results in treated patients showed that classical empirical triple-combination may be suboptimal. (C) 2006 Lippincott Williams & Wilkins.