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在原发性HIV-1感染期间,潜伏感染的静止CD4(+) T细胞池的早期建立。

Early establishment of a pool of latently infected, resting CD4(+) T cells during primary HIV-1 infection.

作者信息

Chun T W, Engel D, Berrey M M, Shea T, Corey L, Fauci A S

机构信息

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

出版信息

Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8869-73. doi: 10.1073/pnas.95.15.8869.

Abstract

The presence of latently infected, resting CD4(+) T cells carrying replication-competent HIV-1 has been demonstrated in chronically infected individuals who are antiretroviral therapy naive as well as in those who are receiving highly active antiretroviral therapy (HAART). It is not clear, however, whether the establishment of a pool of latently infected CD4(+) T cells can be blocked by early initiation of HAART after primary infection. The present study demonstrates that initiation of HAART in infected individuals as early as 10 days after the onset of symptoms of primary HIV-1 infection did not prevent generation of latently infected, resting CD4(+) T cells carrying integrated HIV-1 DNA as well as infectious HIV-1 despite the successful control of plasma viremia shortly after institution of HAART. Furthermore, there was no correlation between either the duration of HAART at the time of study (range: 0.2-17 months) or the time of initiation of HAART after the onset of symptoms of primary HIV-1 infection (range: 0.3-4 months) and the frequencies of resting CD4(+) T cells carrying either integrated HIV-1 DNA or infectious virus. These results underscore the rapidity with which latent reservoirs are established in primary HIV-1 infection and indicate that it is unlikely that early treatment during primary infection can prevent establishment of a pool of latently infected, resting CD4(+) T cells as long as treatment is initiated after plasma viremia becomes evident.

摘要

在未接受抗逆转录病毒治疗的慢性感染个体以及接受高效抗逆转录病毒治疗(HAART)的个体中,均已证实存在携带具有复制能力的HIV-1的潜伏感染静止CD4(+) T细胞。然而,原发性感染后尽早开始HAART是否能阻止潜伏感染的CD4(+) T细胞库的建立尚不清楚。本研究表明,在原发性HIV-1感染症状出现后仅10天就对感染个体开始HAART治疗,尽管在开始HAART治疗后不久血浆病毒血症得到了成功控制,但仍无法阻止携带整合型HIV-1 DNA以及传染性HIV-1的潜伏感染静止CD4(+) T细胞的产生。此外,研究时HAART的持续时间(范围:0.2 - 17个月)或原发性HIV-1感染症状出现后开始HAART的时间(范围:0.3 - 4个月)与携带整合型HIV-1 DNA或传染性病毒的静止CD4(+) T细胞的频率之间均无相关性。这些结果强调了在原发性HIV-1感染中潜伏储存库建立的速度之快,并表明只要在血浆病毒血症明显后开始治疗,原发性感染期间的早期治疗就不太可能阻止潜伏感染静止CD4(+) T细胞库的建立。

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