HIV-1 MESSENGER-RNA IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS AS AN EARLY MARKER OF RISK FOR PROGRESSION TO AIDS

HIV-1 MESSENGER-RNA IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS AS AN EARLY MARKER OF RISK FOR PROGRESSION TO AIDS
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DOI:
10.7326/0003-4819-123-9-199511010-00001
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发表时间:
1995-11-01
影响因子:
39.2
通讯作者:
BALTIMORE, D
BALTIMORE, D
中科院分区:
医学1区
文献类型:
--
作者:
SAKSELA, K;STEVENS, CE;BALTIMORE, D

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目的:在一个长期随访的HIV感染者的大队列中,建立外周血单核细胞中人类免疫缺陷病毒1型(HIV-1)信使RNA(mRNA)表达作为进展为获得性免疫缺陷综合征(AIDS)风险的标志物。设计:对冷冻保存的编码标本进行回顾性检测。设置:纽约血液中心和洛克菲勒大学的研究实验室。患者:150名同性恋男性感染HIV-I,在检测时没有AIDS诊断。测量:使用逆转录酶启动的聚合酶链反应(PCR)定量外周血单个核细胞总RNA中的多剪接和未剪接HIV-I mRNA,并与随后8年的其他实验室数据和临床结果进行比较。尽管HIV-1 mRNA表达通常与免疫状态相关,但它与未来疾病进展相关,与采样时CD 4(+)细胞计数或其下降率无关。HIV-1 mRNA与CD 4(+)细胞计数高于中位数的患者疾病进展的相关性(>624 cells/mm(3))是特别值得注意的;在这个组中的CD 4(+)细胞计数的进一步变化没有统计学意义。外周血单个核细胞中HIV-1 mRNA的表达是未来HIV疾病进展的一个强有力的独立标志,即使是在T细胞亚群正常的人中。
Objective: To establish human immunodeficiency virus type 1 (HIV-1) messenger RNA (mRNA) expression in peripheral blood mononuclear cells as a marker of risk for progression to the acquired immunodeficiency syndrome (AIDS) in a large cohort of HIV-infected persons followed for a prolonged period.Design: Retrospective testing of cryopreserved, coded specimens.Setting: Research laboratories at the New York Blood Center and the Rockefeller University.Patients: 150 homosexual men infected with HIV-I who did not have an AIDS diagnosis at the time of testing.Measurements: Multiply spliced and unspliced HIV-I mRNAs in total peripheral blood mononuclear cell RNA were quantitated using reverse transcriptase-initiated polymerase chain reaction (PCR) and compared with other laboratory data and clinical outcome during the subsequent 8 years.Results: Although HIV-1 mRNA expression generally correlated with immunologic status, it was associated with future disease progression independently of CD4(+) cell counts or their rate of decrease at the time of sampling. The association of HIV-1 mRNA with disease progression in persons with CD4(+) cell counts higher than the median (>624 cells/mm(3)) was particularly noteworthy; further variation in the CD4(+) cell counts within this group was not prognostically significant.Conclusions: The expression of HIV-1 mRNA in peripheral blood mononuclear cells is a strong independent marker for future HIV disease progression, even in persons with normal T-cell subsets.