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JID:结核和进展型HIV共感染者ART治疗后的早期免疫失败与早期死亡相关

2013-09-27 MedSci MedSci原创

虽然资源有限地区的HIV患者接触抗逆转录病毒治疗(ART)的机会不断地增大,但是,有1/4的患者在治疗初期就发生死亡。进展型HIV疾病与ART起始后的早期死亡有关。然而,对于早期死亡的患者,尚不清楚其在死亡之前是否抑制了病毒的复制。人们猜测炎症细胞因子的迅速上升和病原特异性免疫反应(以免疫重建炎症综合症为特点)是引起早期死亡的原因,对于有活性机会性感染的患者来说尤其如此,如结核与进展型HIV。然而

虽然资源有限地区的HIV患者接触抗逆转录病毒治疗(ART)的机会不断地增大,但是,有1/4的患者在治疗初期就发生死亡。进展型HIV疾病与ART起始后的早期死亡有关。然而,对于早期死亡的患者,尚不清楚其在死亡之前是否抑制了病毒的复制。

人们猜测炎症细胞因子的迅速上升和病原特异性免疫反应(以免疫重建炎症综合症为特点)是引起早期死亡的原因,对于有活性机会性感染的患者来说尤其如此,如结核与进展型HIV。然而,结核免疫重建炎症综合症的患者只有少数死于综合征。

相反地,ART中延迟的免疫复苏与HIV相关死亡率的升高有关,这可能对于HIV和结核共感染的患者是有害的。为了证实免疫复苏的失败与ART早期死亡率的升高有关,来自美国宾州大学费雷尔曼医学院感染疾病部门的Shruthi Ravimohan等人进行了一项研究,研究结果在线发表于2013年8月23日的Journal of Infectious Diseases。研究发现,伴有结核的进展型HIV患者治疗后的早期死亡与早期免疫的失败相关。【原文下载】

研究者检测了ART开始4周后的HIV-1RNA和CD4+T细胞数在血浆中的变化与患肺结核成年人早期死亡的关系,并且ART之前的CD4数小于等于125cells/μL,他们采用IFN-γ酶联免疫吸附斑点试验测定纯化蛋白衍生物(PPD)特异性免疫复苏。此外,研究者还测定了IL-6、C反应蛋白和可溶的CD4水平,采用多元回归分析分析了治疗和治疗后4周后的CD4+数和病毒载量水平。

结果显示,ART之前的CD4+细胞数和病毒反应都与早期死亡无关,而早期免疫反应与早期死亡相关。回归分析显示,在治疗前至治疗后4周内,CD4+数每升高20 cells/μL与死亡率下降40%独立相关。

在死亡病例中,PPD特异性免疫复苏水平较低,但是免疫活化水平较高。研究发现,虽然存在病毒学抑制,但是早期免疫的失败与进展型HIV和结核病共感染者开始ART后的早期死亡有关。

原文下载

Ravimohan S, Tamuhla N, Steenhoff AP, Letlhogile R, Makutu DK, Nfanyana K, Rantleru T, Tierney A, Nkakana K, Schwartz AB, Gross R, Macgregor RR, Bellamy SL, Frank I, Weissman D, Bisson GP.Early Immunologic Failure is Associated With Early Mortality Among Advanced HIV-Infected Adults Initiating Antiretroviral Therapy With Active Tuberculosis.J Infect Dis. 2013 Aug 23.



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    2013-09-29 zhaojie88
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