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慢性 HIV 感染的罗马尼亚年轻成年人队列在联合抗逆转录病毒治疗时代的神经认知障碍。

Neurocognitive Impairment in the Combined Antiretroviral Therapy Era in a Romanian Cohort of Young Adults with Chronic HIV Infection.

机构信息

Virology Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

Viral Emerging Diseases Department, Ştefan S. Nicolau Institute of Virology, Bucharest, Romania.

出版信息

AIDS Res Hum Retroviruses. 2020 May;36(5):367-372. doi: 10.1089/AID.2019.0132. Epub 2019 Oct 8.

DOI:10.1089/AID.2019.0132
PMID:31476875
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7232656/
Abstract

HIV-associated neurocognitive disorders (HAND) continue to be reported even in patients with successful antiretroviral treatment. We investigated the prevalence of neurocognitive impairment and possible HIV-associated determinants of cognition in a Romanian cohort of young adults, parenterally infected with HIV during their first years of life. Two hundred fourteen treatment-experienced HIV-positive individuals [median age: 24 years, males: 48%, median duration on combined antiretroviral therapy (cART): 12 years] underwent standard immunologic and virological monitoring and antiretroviral resistance testing using pol gene sequencing in both plasma and, when available, cerebrospinal fluid (CSF) paired samples. Neurocognitive impairment was assessed using a comprehensive neuropsychological test battery, and a global deficit score (GDS) was calculated (cutoff ≥0.5). Cognitive impairment was detected in 35% of the study participants, without any association with sex, median age, CD4 cell count (actual or nadir), CSF and plasma viral load (actual or zenith), AIDS diagnosis, duration of HIV infection, and cART characteristics. Participants carrying resistant viruses tended to be more frequently cognitively impaired ( = 0.36), with a higher median GDS value ( = 0.06) compared with participants harboring wild-type HIV, although the figures did not reach statistical significance. No signs of virological compartmentalization were observed based on CSF versus plasma viral load and on the profile of pol sequences. A moderate rate of mild neurocognitive impairment is still present in young adults with chronic HIV infection acquired in early childhood despite successful cART, without any association with classic markers of HIV infection. New biomarkers reflecting persistent central nervous system inflammation and neuronal injury may be more relevant for the development of HAND.

摘要

HIV 相关神经认知障碍(HAND)即使在接受成功抗逆转录病毒治疗的患者中仍有报道。我们调查了罗马尼亚队列中年轻的 HIV 感染者的认知障碍患病率和可能与 HIV 相关的认知决定因素,这些患者在生命的最初几年通过注射途径感染了 HIV。214 名接受过治疗的 HIV 阳性个体[中位年龄:24 岁,男性:48%,联合抗逆转录病毒治疗(cART)的中位时间:12 年]接受了标准的免疫和病毒学监测,并使用聚合酶基因测序对血浆和(当可用时)配对的脑脊液(CSF)样本进行了抗逆转录病毒耐药性测试。使用综合神经心理学测试电池评估认知障碍,并计算出整体缺陷评分(GDS)(临界值≥0.5)。研究参与者中有 35%存在认知障碍,与性别、中位年龄、CD4 细胞计数(实际或最低点)、CSF 和血浆病毒载量(实际或峰值)、艾滋病诊断、HIV 感染持续时间和 cART 特征无关。携带耐药病毒的参与者往往更频繁地出现认知障碍(=0.36),GDS 值更高(=0.06),与携带野生型 HIV 的参与者相比,尽管这些数字没有达到统计学意义。根据 CSF 与血浆病毒载量和 pol 序列的特征,没有观察到病毒学分隔的迹象。尽管接受了成功的 cART,但在早年感染慢性 HIV 的年轻成年人中,仍存在中度轻度神经认知障碍,且与 HIV 感染的经典标志物无关。反映持续性中枢神经系统炎症和神经元损伤的新生物标志物可能与 HAND 的发展更为相关。