Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection

Kinetics of response in lymphoid tissues to antiretroviral therapy of HIV-1 infection
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DOI:
10.1126/science.276.5314.960
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发表时间:
1997-05-09
期刊:
影响因子:
56.9
通讯作者:
Haase, AT
Haase, AT
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Cavert, W;Notermans, DW;Haase, AT

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在产生和储存人类免疫缺陷病毒1型(HIV-1)的淋巴组织中,用病毒蛋白酶和逆转录酶抑制剂进行三种药物治疗可显著降低病毒负担。这是通过原位杂交和计算机定量分析以前未治疗的成人的一系列扁桃体活检显示的。产生性单核细胞(MNCs)的频率最初减少,半衰期约为1天。令人惊讶的是,被困在滤泡树突状细胞(fdc)上的病毒中HIV-1 RNA的数量几乎同样迅速下降。24周后,每个细胞中HIV-1 RNA拷贝数非常少的MNCs仍然可以检测到,前病毒DNA也是如此;然而,与fdc相关的病毒数量减少了大于或等于3.4 log单位。因此,6个月的强效治疗控制了活跃的复制,并从次级淋巴组织库中清除了99.9%的乙肝病毒。
In lymphoid tissue, where human immunodeficiency virus-type 1 (HIV-1) is produced and stored, three-drug treatment with viral protease and reverse transcriptase inhibitors markedly reduced viral burden. This was shown by in situ hybridization and computerized quantitative analysis of serial tonsil biopsies from previously untreated adults. The frequency of productive mononuclear cells (MNCs) initially diminished with a half-life of about 1 day. Surprisingly, the amount of HIV-1 RNA in virus trapped on follicular dendritic cells (FDCs) decreased almost as quickly. After 24 weeks, MNCs with very few copies of HIV-1 RNA per cell were still detectable, as was proviral DNA; however, the amount of FDC-associated virus decreased by greater than or equal to 3.4 log units. Thus, 6 months of potent therapy controlled active replication and cleared >99.9 percent of virus from the secondary lymphoid tissue reservoir.