Impact of early cART in the gut during acute HIV infection
Impact of early cART in the gut during acute HIV infection
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DOI：
10.1172/jci.insight.87065
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发表时间：
2016-07-07
期刊：
影响因子：
8
通讯作者：
Estes, Jacob D.
中科院分区：
文献类型：
--
作者：
Deleage, Claire;Schuetz, Alexandra;Estes, Jacob D.
HIV感染后早期，胃肠道固有层(LP)中的CD4+T细胞大量减少，并伴有相关的上皮屏障损伤，导致微生物易位、全身炎症和免疫激活。在这项研究中，我们分析了一组泰国急性 HIV 感染患者胃肠道的这些早期事件，并确定了早期联合抗逆转录病毒治疗 (cART) 的效果。处于不同 Fiebig 阶段 (I-V) 的未感染 HIV 以及慢性和急性 HIV 感染的患者接受结肠活检，然后接受 cART。对横断面和纵向结肠活检标本（第0天至第96周）进行免疫组织化学和定量图像分析，以测量胃肠道损伤（多形核细胞浸润）、炎症（Mx1、TNF-α）、免疫激活（Ki-67）和LP中的CD4（+）T细胞群。与未感染 HIV 的对照参与者相比，在 cART 之前的所有急性感染组中，胃肠道损伤、免疫激活和炎症的程度显着增加，LP 中的 CD4(+) T 细胞显着减少。虽然大多数在急性感染期间接受治疗的患者在接受 cART 24 周后消化道炎症得到缓解，免疫激活回到基线水平，但大多数急性感染参与者在接受 cART 96 周后并未恢复其 CD4(+) T 细胞。
Early after HIV infection there is substantial depletion of CD4(+) T cells in the gastrointestinal (GI) tract lamina propria (LP), with associated epithelial barrier damage, leading to microbial translocation and systemic inflammation and immune activation. In this study, we analyzed these early events in the GI tract in a cohort of Thai acute HIV-infected patients and determined the effect of early combination antiretroviral treatment (cART). HIV-uninfected and chronically and acutely HIV-infected patients at different Fiebig stages (I-V) underwent colonic biopsies and then received cART. Immunohistochemistry and quantitative image analysis were performed on cross-sectional and longitudinal colon biopsy specimens (day 0 to week 96) to measure GI tract damage (infiltration of polymorphonuclear cells), inflammation (Mx1, TNF-alpha), immune activation (Ki-67), and the CD4(+) T cell population in the LP. The magnitude of GI tract damage, immune activation, and inflammation was significantly increased, with significantly depleted CD4(+) T cells in the LP in all acutely infected groups prior to cART compared with HIV-uninfected control participants. While most patients treated during acute infection resolved GI tract inflammation and immune activation back to baseline levels after 24 weeks of cART, most acutely infected participants did not restore their CD4(+) T cells after 96 weeks of cART.