Immunological biomarkers predict HIV-1 viral rebound after treatment interruption.
Immunological biomarkers predict HIV-1 viral rebound after treatment interruption.
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DOI：
10.1038/ncomms9495
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发表时间：
2015-10-09
影响因子：
16.6
通讯作者：
Frater J
中科院分区：
文献类型：
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作者：
Hurst J;Hoffmann M;Pace M;Williams JP;Thornhill J;Hamlyn E;Meyerowitz J;Willberg C;Koelsch KK;Robinson N;Brown H;Fisher M;Kinloch S;Cooper DA;Schechter M;Tambussi G;Fidler S;Babiker A;Weber J;Kelleher AD;Phillips RE;Frater J
在传播后的几周内用抗逆转录病毒疗法（ART）治疗HIV-1感染可能会在某些患者中诱导“治疗后控制”（PTC）状态，当ART停止时，病毒血症仍然无法检测到。解释PTC可以帮助我们理解维持病毒持久性的过程。在这里，我们表明，免疫学生物标志物可以预测停止抗逆转录病毒治疗后病毒反弹的时间，通过分析一项随机研究的数据，主要是HIV-1感染合并治疗中断（TI）后48周的抗逆转录病毒治疗（SPARTAC试验）。在ART之前测量的T细胞耗竭标志物PD-1、Tim-3和Lag-3强烈预测病毒血症恢复的时间。这些数据表明，T细胞耗竭标记物可以识别那些潜伏感染的细胞具有更高的病毒转录倾向。我们的研究结果可能为理解PTC的潜在机制开辟新的途径，并最终根除HIV-1。在一些HIV-1感染者中，抗逆转录病毒治疗后病毒血症仍然检测不到，但这些患者中哪些会出现病毒反弹很难预测。在这里，作者表明，治疗前的T细胞耗竭标志物预测病毒反弹的时间较短。
Treatment of HIV-1 infection with antiretroviral therapy (ART) in the weeks following transmission may induce a state of ‘post-treatment control' (PTC) in some patients, in whom viraemia remains undetectable when ART is stopped. Explaining PTC could help our understanding of the processes that maintain viral persistence. Here we show that immunological biomarkers can predict time to viral rebound after stopping ART by analysing data from a randomized study of primary HIV-1 infection incorporating a treatment interruption (TI) after 48 weeks of ART (the SPARTAC trial). T-cell exhaustion markers PD-1, Tim-3 and Lag-3 measured prior to ART strongly predict time to the return of viraemia. These data indicate that T-cell exhaustion markers may identify those latently infected cells with a higher proclivity to viral transcription. Our results may open new avenues for understanding the mechanisms underlying PTC, and eventually HIV-1 eradication. In some HIV-1-infected individuals, viraemia remains undetectable after antiretroviral treatment, but which of these patients will experience viral rebound is difficult to predict. Here the authors show that T cell exhaustion markers before treatment are predictive of shorter time to viral rebound.