Bender Ignacio Rachel A, Dasgupta Sayan, Valdez Rogelio, Pandey Urvashi, Pasalar Siavash, Alfaro Ricardo, Hladik Florian, Gornalusse Germán, Lama Javier R, Duerr Ann
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98104, USA.
Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
iScience. 2022 Nov 19;25(12):105632. doi: 10.1016/j.isci.2022.105632. eCollection 2022 Dec 22.
Prior studies attempting to link biomarkers of immune activation with risk of acquiring HIV have relied on cross sectional samples, most without proximity to HIV acquisition. We created a nested case-control study within the study in Peru, and assessed a panel of plasma immune biomarkers at enrollment and longitudinally, including within a month of diagnosis of primary HIV or matched timepoint in controls. We used machine learning to select biomarkers and sociobehavioral covariates predictive of HIV acquisition. Most biomarkers were indistinguishable between cases and controls one month before HIV diagnosis. However, levels differed between cases and controls at study entry, months to years earlier. Dynamic changes in IL-2, IL-7, IL-10, IP-10 and IL-12, rather than absolute levels, jointly predicted HIV risk when added to traditional risk factors, and there was modest effect modification of biomarkers on association between sociobehavioral risk factors and HIV acquisition.
先前试图将免疫激活生物标志物与感染HIV风险联系起来的研究依赖于横断面样本，大多数样本与HIV感染时间没有关联。我们在秘鲁的这项研究中开展了一项巢式病例对照研究，并在入组时以及纵向评估了一组血浆免疫生物标志物，包括在原发性HIV诊断后一个月内或对照组的匹配时间点。我们使用机器学习来选择可预测HIV感染的生物标志物和社会行为协变量。在HIV诊断前一个月，大多数生物标志物在病例组和对照组之间没有差异。然而，在研究开始时，即数月至数年之前，病例组和对照组的水平有所不同。当将白细胞介素-2（IL-2）、白细胞介素-7（IL-7）、白细胞介素-10（IL-10）、干扰素γ诱导蛋白10（IP-10）和白细胞介素-12（IL-12）的动态变化而非绝对水平添加到传统风险因素中时，它们共同预测了HIV风险，并且生物标志物对社会行为风险因素与HIV感染之间的关联有适度的效应修正作用。
