Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy
Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy
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DOI：
10.1056/nejm199905273402102
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发表时间：
1999-05-27
影响因子：
158.5
通讯作者：
Wolinsky, SM
中科院分区：
文献类型：
--
作者：
Furtado, MR;Callaway, DS;Wolinsky, SM
背景和方法虽然有效的抗逆转录病毒治疗可以控制人类免疫缺陷病毒1型（HIV-1）的感染，但感染性病毒的长期储存库仍然存在于CD 4 + T细胞中。我们通过测量HIV-1复制所必需的细胞相关病毒DNA和信使RNA（mRNA）的水平来研究这种病毒库。大约每6个月，我们从5名长期HIV-1感染的男性外周血单核细胞中获得样本，这些男性在用强效抗逆转录病毒药物治疗期间有20个月或更长时间的血浆HIV-1 RNA水平检测不到，治疗前，血浆HIV-1 RNA水平与细胞相关的未整合HIV-1 DNA和未剪接的病毒mRNA水平相关。治疗后，HIV-1 RNA的血浆水平下降了2.7 log以上，达到无法检测的水平。细胞相关整合和未整合的HIV-1 DNA和mRNA的减少分两个阶段发生。第一阶段发生在治疗的最初500天，其特征是DNA和mRNA水平大幅下降，但未达到不可检测的水平。细胞相关的未整合的病毒DNA、整合的前病毒DNA和未剪接的病毒mRNA的浓度降低了1.25至1.46 log。第二阶段发生在随后的300天或更长时间的治疗期间，其特征是HIV-1 DNA和未剪接mRNA水平的平台期。在最初的快速下降后，未剪接的病毒mRNA（活性病毒转录的措施）的比例稳定，并保持大于零，在每个measurement.Conclusions治疗有效的抗逆转录病毒药物和抑制血浆HIV-1 RNA检测不到的水平为20个月或更长时间，HIV-1转录持续在外周血单核细胞。除非HIV DNA和mRNA的准稳态水平最终随着治疗时间的延长而消失，否则这些发现表明，HIV-1感染无法通过目前的治疗根除。（N Engl J Med 1999;340：1614-22.）(C)1999年，马萨诸塞州医学会。
Background and Methods Although potent antiretroviral therapy can control infection with human immunodeficiency virus type 1 (HIV-1), a long-lived reservoir of infectious virus persists in CD4+ T cells. We investigated this viral reservoir by measuring the levels of cell-associated viral DNA and messenger RNA (mRNA) that are essential for HIV-1 replication. Approximately every 6 months, we obtained samples of peripheral-blood mononuclear cells from five men with long-standing HIV-1 infection who had had undetectable levels of plasma HIV-1 RNA for 20 months or more during treatment with potent antiretroviral drugs.Results Before treatment, plasma levels of HIV-1 RNA correlated with the levels of cell-associated unintegrated HIV-1 DNA and unspliced viral mRNA. After treatment, plasma levels of HIV-1 RNA fell by more than 2.7 log to undetectable levels. The decrease in cell-associated integrated and unintegrated HIV-1 DNA and mRNA occurred in two phases. The first phase occurred during the initial 500 days of treatment and was characterized by substantial decreases in the levels of DNA and mRNA, but not to undetectable levels. The concentrations of cell-associated unintegrated viral DNA, integrated proviral DNA, and unspliced viral mRNA decreased by 1.25 to 1.46 log. The second phase occurred during the subsequent 300 days or more of treatment and was characterized by a plateau in the levels of HIV-1 DNA and unspliced mRNA. After an initial rapid decline, the ratio of unspliced to multiply spliced viral mRNA (a measure of active viral transcription) stabilized and remained greater than zero at each measurement.Conclusions Despite treatment with potent antiretroviral drugs and the suppression of plasma HIV-1 RNA to undetectable levels for 20 months or more, HIV-1 transcription persists in peripheral-blood mononuclear cells. Unless the quasi-steady state levels of HIV DNA and mRNA eventually disappear with longer periods of therapy, these findings suggest that HIV-1 infection cannot be eradicated with current treatments. (N Engl J Med 1999;340:1614-22.) (C) 1999, Massachusetts Medical Society.