Zhang L, Chung C, Hu B S, He T, Guo Y, Kim A J, Skulsky E, Jin X, Hurley A, Ramratnam B, Markowitz M, Ho D D
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.
J Clin Invest. 2000 Oct;106(7):839-45. doi: 10.1172/JCI10565.
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.
尽管接受了高效抗逆转录病毒疗法（HAART）的长期治疗，但具有传染性的HIV-1仍在继续复制，并潜伏在静息记忆CD4(+) T淋巴细胞中，这成为根除HIV-1的主要障碍。因此，在停用HAART后迅速出现病毒反弹并不奇怪。然而，反弹病毒的性质仍不明确。我们现在报告了8例患者中反弹病毒的基因特征，这些患者在大约3年的HAART治疗期间血浆病毒血症一直检测不到。利用HIV-1 env中广泛的长度多态性，我们发现，在5例治疗期间未出现HIV-1复制的患者中，反弹病毒与从潜伏库中分离出的病毒相同。在另外3例患者中，其中2例血浆病毒血症已清除，但仍有一些残留病毒复制，反弹病毒在基因上与潜伏库病毒不同，而是与在治疗过程中在淋巴组织中检测到的次要病毒变体相对应。我们得出结论，在HAART明显完全抑制HIV-1的情况下，治疗停止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HIV-1持续的低水平复制触发的，这种复制可能发生在淋巴组织中。
