Concurrent measures of total and integrated HIV DNA monitor reservoirs and ongoing replication in eradication trials.
Concurrent measures of total and integrated HIV DNA monitor reservoirs and ongoing replication in eradication trials.
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DOI：
10.1097/qad.0b013e32835a5c2f
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发表时间：
2012-11-28
期刊：
影响因子：
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通讯作者：
O'Doherty U
中科院分区：
文献类型：
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作者：
Mexas AM;Graf EH;Pace MJ;Yu JJ;Papasavvas E;Azzoni L;Busch MP;Di Mascio M;Foulkes AS;Migueles SA;Montaner LJ;O'Doherty U
目的：针对HIV储存库的兴趣正在推动可能减少储存库大小和/或诱导病毒复制的试验。因此，我们的目标是制定策略，以敏感地测量这些参数的变化在患者接受和停止抗逆转录病毒治疗（ART）。实现这些目标可能有助于评估未来临床试验的效果。设计：为了确定总HIV和整合HIV DNA的测量值与它们作为库大小和正在进行复制的标记物之间的关系，在ART治疗的第一年、长期有效的ART治疗期间和针对库的临床试验期间测量了这些参数。方法：采用定量PCR技术对患者标本进行HIV总DNA和整合DNA检测。同时监测CD4+ T细胞计数和血浆病毒血症。结果：在抗逆转录病毒治疗的第一年，未整合的HIV DNA无法检测到。在接受抗逆转录病毒治疗的控制良好的患者中，总HIV和综合HIV DNA水平一般相等，低水平的血浆病毒血症与综合措施的相关性最好。最后，在干扰素-α单药治疗期间控制血浆病毒血症（< 400拷贝/ml）的患者，随着时间的推移，整合HIV DNA水平下降，但不是总HIV DNA水平下降，而总HIV DNA与整合HIV DNA的比例上升。结论：我们的研究结果表明，非整合HIV DNA的出现反映了残留的HIV表达和重新转录，为干扰素-α减少HIV库的机制提供了新的见解。我们的结论是，同时测量总HIV和整合HIV DNA提供了关于库大小和正在进行的HIV试验复制的信息。
Objectives:Interest in targeting HIV reservoirs is fueling trials that may decrease reservoir size and/or induce viral replication. Therefore, we aimed to develop strategies to sensitively measure changes in these parameters in patients on and off antiretroviral therapy (ART). Achieving these goals may help evaluate the effects of future clinical trials.Design:To determine the relationship between measurements of total and integrated HIV DNA and their role as markers of reservoir size and ongoing replication, these parameters were measured during the first year of ART, during long-term effective ART, and during a clinical trial aimed at targeting reservoirs.Methods:Total and integrated HIV DNA were measured in patient samples using quantitative PCR techniques. CD4+ T cell counts and plasma viremia were also monitored.Results:Unintegrated HIV DNA became undetectable during the first year of ART. Total and integrated HIV DNA levels were generally equal in well controlled patients on ART, and low-level plasma viremia correlated best with integration measures. Finally, patients who controlled plasma viremia (< 400 copies/ml) during interferon-α monotherapy exhibited a decrease in the level of integrated but not total HIV DNA and a rise in the ratio of total to integrated HIV DNA over time.Conclusion:Our findings suggest that appearance of unintegrated HIV DNA reflects residual HIV expression and de-novo reverse transcription, providing insight into the mechanism by which interferon-α reduces the HIV reservoir. We conclude that concurrent measurements of total and integrated HIV DNA provide information regarding reservoir size and ongoing replication in trials targeting HIV.