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本文引用的文献

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Causes and Timing of Mortality and Morbidity Among Late Presenters Starting Antiretroviral Therapy in the REALITY Trial.REALITY 试验中晚期开始抗逆转录病毒治疗者的死亡率和发病率的原因和时间。
Clin Infect Dis. 2018 Mar 4;66(suppl_2):S132-S139. doi: 10.1093/cid/cix1141.
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The Enduring Challenge of Advanced HIV Infection.晚期HIV感染的持久挑战
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Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[F]fluoro-D-glucose positron emission and computed tomography.利用2-脱氧-2-[F]氟-D-葡萄糖正电子发射断层扫描和计算机断层扫描对进展性HIV相关结核病进行特征分析。
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Curr Opin HIV AIDS. 2016 Mar;11(2):191-200. doi: 10.1097/COH.0000000000000241.
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Infection with Mycobacterium tuberculosis induces the Warburg effect in mouse lungs.结核分枝杆菌感染可诱导小鼠肺部发生瓦伯格效应。
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18F-氟代脱氧葡萄糖正电子发射断层扫描-计算机断层扫描在人类免疫缺陷病毒相关免疫重建炎症综合征中的代谢活性增加。

Increased Metabolic Activity on 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Human Immunodeficiency Virus-Associated Immune Reconstitution Inflammatory Syndrome.

机构信息

Center for Infectious Diseases Imaging, Clinical Center, National Institutes of Health (NIH).

Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda.

出版信息

Clin Infect Dis. 2019 Jan 7;68(2):229-238. doi: 10.1093/cid/ciy454.

DOI:10.1093/cid/ciy454
PMID:30215671
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6321853/
Abstract

BACKGROUND

Immune reconstitution inflammatory syndrome (IRIS) represents an unexpected inflammatory response shortly after initiation of antiretroviral therapy (ART) in some human immunodeficiency virus (HIV)-infected patients with underlying neoplasia or opportunistic infections, including tuberculosis. We hypothesized that IRIS is associated with increased glycolysis and that 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) could help identify high-risk subjects.

METHODS

In this prospective cohort study, 30 HIV-infected patients (CD4+ count <100 cells/µL) underwent FDG-PET/CT scans at baseline and 4-8 weeks after ART initiation. Ten patients developed IRIS (6 mycobacterial).

RESULTS

At baseline, total glycolytic activity, total lesion volume, and maximum standardized uptake values (SUVs) of pathologic FDG uptake (reflective of opportunistic disease burden) were significantly higher in IRIS vs non-IRIS (P = .010, .017, and .029, respectively) and significantly correlated with soluble inflammatory biomarkers (interferon-γ, myeloperoxidase, tumor necrosis factor, interleukin 6, soluble CD14). Baseline bone marrow (BM) and spleen FDG uptake was higher in mycobacterial IRIS specifically. After ART initiation, BM and spleen mean SUV decreased in non-IRIS (P = .004, .013) but not IRIS subjects. Our results were supported by significantly higher glucose transporter 1 (Glut-1) expression of CD4+ cells and monocytes after ART initiation in IRIS/mycobacterial IRIS compared with non-IRIS patients.

CONCLUSIONS

We conclude that increased pathologic metabolic activity on FDG-PET/CT prior to ART initiation is associated with IRIS development and correlates with inflammatory biomarkers. Abnormally elevated BM and spleen metabolism is associated with mycobacterial IRIS, HIV viremia, and Glut-1 expression on CD4+ cells and monocytes.

CLINICAL TRIALS REGISTRATION

NCT02147405.

摘要

背景

免疫重建炎症综合征（IRIS）代表了一些患有潜在肿瘤或机会性感染（包括结核病）的人类免疫缺陷病毒（HIV）感染患者在开始抗逆转录病毒治疗（ART）后不久出现的意外炎症反应。我们假设 IRIS 与糖酵解增加有关，18F-氟脱氧葡萄糖（FDG）正电子发射断层扫描-计算机断层扫描（PET/CT）可以帮助识别高风险患者。

方法

在这项前瞻性队列研究中，30 名 HIV 感染患者（CD4+计数<100 个/μL）在开始 ART 前后 4-8 周进行 FDG-PET/CT 扫描。10 名患者发生了 IRIS（6 例分枝杆菌）。

结果

在基线时，IRIS 组的总糖酵解活性、总病变体积和最大标准化摄取值（SUV）（反映机会性疾病负担）明显高于非 IRIS 组（P=0.010、0.017 和 0.029），并与可溶性炎症生物标志物（干扰素-γ、髓过氧化物酶、肿瘤坏死因子、白细胞介素 6、可溶性 CD14）显著相关。基线骨髓（BM）和脾脏 FDG 摄取在分枝杆菌 IRIS 中更高。在 ART 开始后，非 IRIS 组的 BM 和脾脏平均 SUV 降低（P=0.004、0.013），但 IRIS 组无变化。我们的结果得到了以下支持：与非 IRIS 患者相比，IRIS/分枝杆菌 IRIS 患者在开始 ART 后 CD4+细胞和单核细胞的葡萄糖转运蛋白 1（Glut-1）表达显著升高。

结论

我们得出结论，在开始 ART 之前，FDG-PET/CT 上病理性代谢活性增加与 IRIS 发展有关，并与炎症生物标志物相关。BM 和脾脏代谢异常升高与分枝杆菌 IRIS、HIV 病毒血症以及 CD4+细胞和单核细胞上的 Glut-1 表达有关。

临床试验注册

NCT02147405。