皮下注射白细胞介素-2 随机国际试验评估中的细菌性肺炎预测因子 (ESPRIT)。

Predictors of bacterial pneumonia in Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT).

机构信息

National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia.

出版信息

HIV Med. 2011 Apr;12(4):219-27. doi: 10.1111/j.1468-1293.2010.00875.x. Epub 2010 Aug 31.

DOI:10.1111/j.1468-1293.2010.00875.x

PMID:20812949

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3048911/

Abstract

BACKGROUND AND OBJECTIVES

Bacterial pneumonia still contributes to morbidity/mortality in HIV infection despite effective combination antiretroviral therapy (cART). Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT), a trial of intermittent recombinant interleukin-2 (rIL-2) with cART vs. cART alone (control arm) in HIV-infected adults with CD4 counts ≥300cells/μL, offered the opportunity to explore associations between bacterial pneumonia and rIL-2, a cytokine that increases the risk of some bacterial infections.

METHODS

Baseline and time-updated factors associated with first-episode pneumonia on study were analysed using multivariate proportional hazards regression models. Information on smoking/pneumococcal vaccination history was not collected.

RESULTS

IL-2 cycling was most intense in years 1-2. Over ≈7 years, 93 IL-2 [rate 0.67/100 person-years (PY)] and 86 control (rate 0.63/100 PY) patients experienced a pneumonia event [hazard ratio (HR) 1.06; 95% confidence interval (CI) 0.79, 1.42; P=0.68]. Median CD4 counts prior to pneumonia were 570cells/μL (IL-2 arm) and 463cells/μL (control arm). Baseline risks for bacterial pneumonia included older age, injecting drug use, detectable HIV viral load (VL) and previous recurrent pneumonia; Asian ethnicity was associated with decreased risk. Higher proximal VL (HR for 1 log(10) higher VL 1.28; 95% CI 1.11, 1.47; P<0.001) was associated with increased risk; higher CD4 count prior to the event (HR per 100 cells/μL higher 0.94; 95% CI 0.89, 1.0; P=0.04) decreased risk. Compared with controls, the hazard for a pneumonia event was higher if rIL-2 was received <180 days previously (HR 1.66; 95% CI 1.07, 2.60; P=0.02) vs.≥180 days previously (HR 0.98; 95% CI 0.70, 1.37; P=0.9). Compared with the control group, pneumonia risk in the IL-2 arm decreased over time, with HRs of 1.41, 1.71, 1.16, 0.62 and 0.84 in years 1, 2, 3-4, 5-6 and 7, respectively.

CONCLUSIONS

Bacterial pneumonia rates in cART-treated adults with moderate immunodeficiency are high. The mechanism of the association between bacterial pneumonia and recent IL-2 receipt and/or detectable HIV viraemia warrants further exploration.

摘要

背景和目的

尽管有有效的联合抗逆转录病毒疗法（cART），细菌性肺炎仍然导致 HIV 感染患者的发病率和死亡率。皮下注射白细胞介素-2 随机国际试验（ESPRIT）评估了间歇性重组白细胞介素-2（rIL-2）与 cART 治疗 vs. cART 治疗（对照组）在 CD4 计数≥300 个/μL 的 HIV 感染成人中的疗效，该试验为探索白细胞介素-2（一种增加某些细菌感染风险的细胞因子）与细菌性肺炎之间的相关性提供了机会。

方法

采用多变量比例风险回归模型分析研究中首次发生肺炎的基线和时间更新因素。未收集吸烟/肺炎球菌疫苗接种史信息。

结果

IL-2 循环在第 1-2 年最为剧烈。在大约 7 年的时间里，93 名 IL-2 [发生率 0.67/100 人年（PY）]和 86 名对照组患者 [发生率 0.63/100 PY]经历了肺炎事件 [风险比（HR）1.06；95%置信区间（CI）0.79, 1.42；P=0.68]。肺炎发生前的中位 CD4 计数分别为 570 个/μL（IL-2 组）和 463 个/μL（对照组）。细菌性肺炎的基线风险包括年龄较大、使用注射毒品、可检测的 HIV 病毒载量（VL）和既往复发性肺炎；亚洲种族与较低的风险相关。较高的近端 VL（每 log(10)升高 1 的 HR 为 1.28；95%CI 为 1.11, 1.47；P<0.001）与较高的风险相关；事件前更高的 CD4 计数（每增加 100 个/μL 的 HR 为 0.94；95%CI 为 0.89, 1.0；P=0.04）降低了风险。与对照组相比，如果 rIL-2 在前 180 天内接受治疗（HR 1.66；95%CI 1.07, 2.60；P=0.02），而不是在前 180 天内接受治疗（HR 0.98；95%CI 0.70, 1.37；P=0.9），则发生肺炎事件的风险更高。与对照组相比，IL-2 组的肺炎风险随着时间的推移而降低，第 1、2、3-4、5-6 和 7 年的 HR 分别为 1.41、1.71、1.16、0.62 和 0.84。