Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues
Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues
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DOI：
10.1073/pnas.1318249111
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发表时间：
2014-02-11
影响因子：
11.1
通讯作者：
Schacker, Timothy W.
中科院分区：
文献类型：
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作者：
Fletcher, Courtney V.;Staskus, Kathryn;Schacker, Timothy W.
抗逆转录病毒治疗可以将外周血中的HIV-1降低到无法检测到的水平，但治疗对抑制淋巴组织储存库中的复制的有效性尚未确定。在这里，我们在治疗前和治疗6个月期间采集的淋巴结样本中显示，五种最常用的抗逆转录病毒药物的组织浓度远低于外周血中的浓度。这些较低的浓度与持续的病毒复制有关，通过滤泡树突状细胞网络病毒粒子池的缓慢衰退或增加来衡量，并与在高产感染细胞中检测到病毒RNA有关。与明显低于最佳药物浓度相关的持续复制的证据表明，需要开发和评估新的治疗策略，以完全抑制淋巴组织中的病毒复制。这些策略可以避免由低水平病毒复制直接或间接驱动的慢性免疫激活的长期临床后果，从而改善免疫重建。
Antiretroviral therapy can reduce HIV-1 to undetectable levels in peripheral blood, but the effectiveness of treatment in suppressing replication in lymphoid tissue reservoirs has not been determined. Here we show in lymph node samples obtained before and during 6 mo of treatment that the tissue concentrations of five of the most frequently used antiretroviral drugs are much lower than in peripheral blood. These lower concentrations correlated with continued virus replication measured by the slower decay or increases in the follicular dendritic cell network pool of virions and with detection of viral RNA in productively infected cells. The evidence of persistent replication associated with apparently suboptimal drug concentrations argues for development and evaluation of novel therapeutic strategies that will fully suppress viral replication in lymphatic tissues. These strategies could avert the long-term clinical consequences of chronic immune activation driven directly or indirectly by low-level viral replication to thereby improve immune reconstitution.