A long-term latent reservoir for HIV-1: discovery and clinical implications
A long-term latent reservoir for HIV-1: discovery and clinical implications
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DOI：
10.1093/jac/dkh292
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发表时间：
2004-07-01
影响因子：
5.2
通讯作者：
Siliciano, RF
中科院分区：
文献类型：
--
作者：
Siliciano, JD;Siliciano, RF
尽管高效抗逆转录病毒疗法（HAART）在治疗HIV-1感染方面取得了显著的成功，但现在看来，这种感染本质上是单用抗逆转录病毒疗法无法治愈的。主要原因是病毒可以在静息记忆CD 4细胞中以潜伏形式持续存在。当携带HIV-1基因组完整拷贝的受感染的CD 4（+）淋巴母细胞恢复到静息记忆状态时，这些细胞就会出现。在这种静息状态下，CD 4细胞对病毒基因表达的允许性最低，受感染的记忆细胞可以存活多年。在再次暴露于相关抗原或其他活化刺激物后，这些细胞可以开始再次产生病毒。稳定储层的存在在几个方面改变了处理策略。HAART不再以根除为目标。此外，该储存库还可作为野生型病毒和治疗期间出现的耐药变异的永久档案。因此，一旦对特定药物产生耐药性，患者将始终携带该耐药性。治疗中断会导致原始野生型病毒的重新出现，这种病毒的复制能力往往比耐药病毒更好。虽然HAART不能根除感染，但目前的治疗方案确实接近阻止病毒进化。在接受HAART治疗的患者血浆中发现的低水平游离病毒与潜伏库中的病毒相似，不含新的耐药突变。因此，尽管HAART不能根除，但用抗逆转录病毒药物终生控制感染是可能的。
Despite the remarkable success of highly active antiretroviral therapy (HAART) for the treatment of HIV-1 infection, it now appears that the infection is intrinsically incurable with antiretroviral therapy alone. The major reason is that the virus can persist in a latent form in resting memory CD4 cells. These cells arise when infected CD4(+) lymphoblasts carrying an integrated copy of the HIV-1 genome revert back to a resting memory state. In this resting state, CD4 cells are minimally permissive for virus gene expression, and infected memory cells can survive for many years. Following re-exposure to the relevant antigen or other activating stimuli, these cells can begin to produce virus again. The existence of a stable reservoir has altered treatment strategies in several ways. HAART is no longer given with the goal of eradication. In addition, the reservoir serves as a permanent archive for wild-type virus and for drug-resistant variants that arise during treatment. Thus, once resistance to a particular drug arises, the patient will always carry that resistance. Interruption in treatment results in the re-emergence of the original wild-type virus, which often replicates better than drug-resistant virus. Although HAART cannot eradicate the infection, current regimens do come close to stopping virus evolution. Free viruses found in the plasma at low levels in patients on HAART resemble viruses in the latent reservoir and do not contain new drug resistance mutations. Thus although HAART cannot produce eradication, lifetime control of the infection with antiretroviral drugs may be possible.