■HIV感染者(PLWH)中进行性多灶性白质脑病(PML)的发生率为2%-4%。目前,对于PLWH中PML的治疗没有有效的治疗策略,导致高达50%的死亡率。本研究旨在确定HIV感染者PML的死亡危险因素和预后标志物。
■2015年1月1日至2022年10月1日在上海进行了与艾滋病相关的PML个体的回顾性队列研究。中国。纳入首次诊断为PML的PLWH。采用Kaplan-Meier曲线和Cox回归分析生存率及其预测因子。使用基于珠的多重测定在预存样品中测量血液和脑脊液(CSF)中的炎症标志物和免疫检查点抑制剂的水平。使用ELISA测定吲哚胺2,3-双加氧酶。
■71名受试者中有20名在PML发病前开始抗逆转录病毒治疗(ART),在此期间没有患者停止ART。总的来说,34例患者(47.9%)有机会性感染(OI),中位CD4+T细胞计数为73.0(33.0-149.0)细胞/μL.6个月时的估计生存概率为78%(95%保密间隔[CI]:0.63-0.85)。OIs,低CD4+T细胞计数与较低的估计6个月生存率相关(风险比8.01,95%CI:1.80-35.00,P=0.006和5.01,95%CI:1.57-16.03,p=0.007).非存活组脑脊液吲哚胺2,3-双加氧酶活性高于存活组(p<0.05)。
■现代ART时代与AIDS相关的PML的存活率高于十年前的存活率。低CD4+T细胞计数,OIs,均与艾滋病相关PML患者的死亡相关。IDO在与艾滋病相关的PML中的作用值得进一步调查。
The incidence of progressive multifocal leukoencephalopathy (PML) in people living with HIV (PLWH) is 2%-4%. Currently, there is no effective therapeutic strategy for the treatment of PML in PLWH, resulting in a mortality of up to 50%. This study aimed to identify risk factors of death and prognostic markers in people living with HIV with PML.
A retrospective cohort study of AIDS-related PML individuals was conducted from January 1, 2015, to October 1, 2022, in Shanghai,
China. PLWH who were diagnosed with PML for the first time were included. Kaplan-Meier curve and Cox regression were used to analyze the survival and its predictors. Levels of inflammatory markers and immune checkpoint inhibitors in blood and cerebrospinal fluid (CSF) were measured in the prestored samples using bead-based multiplex assay Indolamine 2,3-dioxygenase was determined using ELISA.
Twenty of 71 subjects had initiated antiretroviral therapy (ART) before PML onset and no patients discontinued ART during this period. In total, 34 patients (47.9%) had opportunistic infections (OIs), the median CD4+ T cell count was 73.0 (33.0-149.0) cells/μL. The estimated probability of survival at six months was 78% (95% confidential intervals [CIs]:0.63-0.85). OIs, low CD4+ T cell count were associated with lower estimated six-month survival (hazard ratio 8.01, 95% CIs: 1.80-35.00, P=0.006 and 5.01, 95% CIs:1.57-16.03, p=0.007). Indolamine 2,3-dioxygenase activity in CSF of non-survivors group were higher than survivors group (p<0.05).
The survival rate of AIDS-related PML in the modern ART era was higher than the survival rate a decade ago. Low CD4+T cell count, OIs, were all associated with death of individuals with AIDS-related PML. The role of IDO in AIDS-related PML warrant further investigation.