Genetic characterization of rebounding HIV-1 after cessation of highly active antiretroviral therapy.
Genetic characterization of rebounding HIV-1 after cessation of highly active antiretroviral therapy.
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DOI：
10.1172/jci10565
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发表时间：
2000-10
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影响因子：
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通讯作者：
Linqi Zhang;Chris Chung;Bor-shen Hu;T. He;Yong Guo;A. Kim;Eva Skulsky;Xia Jin;A. Hurley;B. Ramratnam;M. Markowitz;D. Ho
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文献类型：
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作者：
Linqi Zhang;Chris Chung;Bor-shen Hu;T. He;Yong Guo;A. Kim;Eva Skulsky;Xia Jin;A. Hurley;B. Ramratnam;M. Markowitz;D. Ho
尽管长期接受高效抗逆转录病毒疗法(HAART)治疗，但传染性HIV-1继续复制并潜伏在静止的记忆CD4(+)T淋巴细胞中，为根除HIV-1制造了主要障碍。因此，在终止HAART后观察到病毒迅速反弹也就不足为奇了。然而，反弹病毒的性质仍未确定。我们现在报告了8名患者的反弹病毒的基因特征，在大约3年的HAART中，这些患者的血浆病毒血症是无法检测到的。利用HIV-1 env的广泛长度多态，我们发现在5名在治疗过程中没有表现出HIV-1复制的患者中，反弹病毒与从潜伏库分离的病毒相同。在另外三名患者中，其中两名患者没有血浆病毒血症，但显示出一些残留的病毒复制，反弹病毒在基因上不同于潜伏的蓄积病毒，与治疗过程中在淋巴组织中检测到的微小病毒变异相对应。我们的结论是，在HAART明显完全抑制HIV-1的病例中，停止治疗后的病毒反弹可能源于潜伏库中病毒的激活。然而，在化疗不完全抑制的患者中，病毒反弹可能是由持续的、低水平的HIV-1复制引发的，可能发生在淋巴组织中。
Despite prolonged treatment with highly active antiretroviral therapy (HAART), infectious HIV-1 continues to replicate and to reside latently in resting memory CD4(+) T lymphocytes, creating a major obstacle to HIV-1 eradication. It is therefore not surprising to observe a prompt viral rebound after discontinuation of HAART. The nature of the rebounding virus, however, remains undefined. We now report on the genetic characterization of rebounding viruses in eight patients in whom plasma viremia was undetectable throughout about 3 years of HAART. Taking advantage of the extensive length polymorphism in HIV-1 env, we found that in five patients who did not show HIV-1 replication during treatment, the rebound virus was identical to those isolated from the latent reservoir. In three other patients, two of whom had been free of plasma viremia but had showed some residual viral replication, the rebound virus was genetically different from the latent reservoir virus, corresponding instead to minor viral variants detected during the course of treatment in lymphoid tissues. We conclude that in cases with apparent complete HIV-1 suppression by HAART, viral rebound after cessation of therapy could have originated from the activation of virus from the latent reservoir. In patients with incomplete suppression by chemotherapy, however, the viral rebound is likely triggered by ongoing, low-level replication of HIV-1, perhaps occurring in lymphoid tissues.