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PNAS:HIV-1在长期接受抗逆转录病毒疗法的病人体内持续存在

来源:EurekAlert 2013-11-26 09:32

艾滋病病毒1型(HIV-1)是否会在接受抑制性抗逆转录病毒疗法的病人体内继续复制并且这种复制是否造成了艾滋病病毒1型(HIV-1)在病人体内持续存,答案仍不清楚,但是一项对接受长期抗逆转录病毒疗法的8名病人的研究揭示出,随着时间推移,这种病毒很少或者没有在潜伏感染的T细胞中进化,这提示并不存在不断的病毒复制。

联合高效抗逆转录病毒疗法(cART)抑制了艾滋病病毒1型(HIV-1)在血液中的浓度,但是没有完全清除这种病毒。为了更好地理解在联合高效抗逆转录病毒疗法(cART)治疗期间艾滋病病毒1型(HIV-1)持续存在的机制,Lina Josefsson及其同事分析了来自接受联合高效抗逆转录病毒疗法(cART)4到12年的8名病人的血样和肠相关淋巴样组织(GALT)——它们是这种病毒可能的储存库——中分离出的CD4+ T细胞和骨髓细胞中的艾滋病病毒1型(HIV-1) DNA。

这组作者发现,在长期抗逆转录病毒治疗之后,记忆T细胞和原生T细胞都有艾滋病病毒1型(HIV-1)的DNA。这组作者还观察到,与在感染后的1-3个月开始治疗的病人的细胞相比,从感染之后的1年以上开始治疗的病人收集到的T细胞有更高的感染频率,这提示早治疗可能导致HIV-1型的储存库较小。此外,开始联合高效抗逆转录病毒疗法(cART)治疗前在血浆中的艾滋病病毒1型(HIV-1)种群在遗传上类似于接受了4-12年的抗逆转录病毒疗法的受感染T细胞中的病毒种群。

这组作者说,这些发现提示病毒复制可能不是艾滋病病毒1型(HIV-1)在接受联合高效抗逆转录病毒疗法(cART)的病人体内持续存在的主要原因。(生物谷Bioon.com)

生物谷推荐的英文摘要

Proceedings of the National Academy of the Sciences of the United States of America              doi: 10.1073/pnas.1308313110

The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time

Lina Josefssona,b,1, Susanne von Stockenstroma,b, Nuno R. Fariac, Elizabeth Sinclaird, Peter Bacchettie, Maudi Killiand, Lorrie Eplingd, Alice Tand, Terence Hod, Philippe Lemeyc, Wei Shaof, Peter W. Huntd, Ma Somsoukd, Will Wylieg, Daniel C. Douekg, Lisa Loebd, Jeff Custerd, Rebecca Hohd, Lauren Pooled, Steven G. Deeksd, Frederick Hechtd,2, and Sarah Palmera,b,h,i,2

The source and dynamics of persistent HIV-1 during long-term combinational antiretroviral therapy (cART) are critical to understanding the barriers to curing HIV-1 infection. To address this issue, we isolated and genetically characterized HIV-1 DNA from na?ve and memory T cells from peripheral blood and gut-associated lymphoid tissue (GALT) from eight patients after 4–12 y of suppressive cART. Our detailed analysis of these eight patients indicates that persistent HIV-1 in peripheral blood and GALT is found primarily in memory CD4+ T cells [CD45RO+/CD27(+/?)]. The HIV-1 infection frequency of CD4+ T cells from peripheral blood and GALT was higher in patients who initiated treatment during chronic compared with acute/early infection, indicating that early initiation of therapy results in lower HIV-1 reservoir size in blood and gut. Phylogenetic analysis revealed an HIV-1 genetic change between RNA sequences isolated before initiation of cART and intracellular HIV-1 sequences from the T-cell subsets after 4–12 y of suppressive cART in four of the eight patients. However, evolutionary rate analyses estimated no greater than three nucleotide substitutions per gene region analyzed during all of the 4–12 y of suppressive therapy. We also identified a clearly replication-incompetent viral sequence in multiple memory T cells in one patient, strongly supporting asynchronous cell replication of a cell containing integrated HIV-1 DNA as the source. This study indicates that persistence of a remarkably stable population of infected memory cells will be the primary barrier to a cure, and, with little evidence of viral replication, this population could be maintained by homeostatic cell proliferation or other processes.

推荐阅读:

生物谷特别策划:关注艾滋病 关注抗艾研发进展特别专题  http://www.bioon.com/z/HIV201311/

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