Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Region Västra Götaland, Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, Sweden.
Clin Infect Dis. 2022 Aug 31;75(3):493-502. doi: 10.1093/cid/ciab943.
The aim of this large multicenter study was to determine variations in cerebrospinal fluid (CSF) HIV-RNA in different phases of untreated human immunodeficiency virus type 1 (HIV-1) infection and its associations with plasma HIV-RNA and other biomarkers.
Treatment naive adults with available CSF HIV-RNA quantification were included and divided into groups representing significant disease phases. Plasma HIV-RNA, CSF white blood cell count (WBC), neopterin, and albumin ratio were included when available.
In total, 1018 patients were included. CSF HIV-RNA was in median (interquartile range [IQR]) 1.03 log10 (0.37-1.86) copies/mL lower than in plasma, and correlated with plasma HIV-RNA (r = 0.44, P < .01), neopterin concentration in CSF (r = 0.49, P < .01) and in serum (r = 0.29, P < .01), CSF WBC (r = 0.34, P < .01) and albumin ratio (r = 0.25, P < .01). CSF HIV-RNA paralleled plasma HIV-RNA in all groups except neuroasymptomatic patients with advanced immunodeficiency (CD4 < 200) and patients with HIV-associated dementia (HAD) or opportunistic central nervous system (CNS) infections. Patients with HAD had the highest CSF HIV-RNA (in median [IQR] 4.73 (3.84-5.35) log10 copies/mL). CSF > plasma discordance was found in 126 of 972 individuals (13%) and varied between groups, from 1% in primary HIV, 11% in neuroasymptomatic groups, up to 30% of patients with HAD.
Our study confirms previous smaller observations of variations in CSF HIV-RNA in different stages of HIV disease. Overall, CSF HIV-RNA was approximately 1 log10 copies/mL lower in CSF than in plasma, but CSF discordance was found in a substantial minority of subjects, most commonly in patients with HAD, indicating increasing CNS compartmentalization paralleling disease progression.
本项大型多中心研究旨在确定未经治疗的人类免疫缺陷病毒 1 型(HIV-1)感染不同阶段的脑脊液(CSF)中 HIV-RNA 的变化,及其与血浆 HIV-RNA 和其他生物标志物的关联。
纳入了可提供 CSF HIV-RNA 定量检测的初治成人患者,并根据代表不同疾病阶段的组别进行分组。当有条件时,纳入血浆 HIV-RNA、CSF 白细胞计数(WBC)、新蝶呤和白蛋白比值。
共纳入 1018 例患者。CSF HIV-RNA 中位数(四分位距 [IQR])比血浆低 1.03 log10(0.37-1.86)拷贝/ml,与血浆 HIV-RNA 相关(r=0.44,P<.01),与 CSF 中的新蝶呤浓度相关(r=0.49,P<.01)和血清中的新蝶呤浓度相关(r=0.29,P<.01),与 CSF WBC 相关(r=0.34,P<.01)和白蛋白比值相关(r=0.25,P<.01)。除了无症状且免疫功能低下(CD4<200)的患者和 HIV 相关痴呆(HAD)或机会性中枢神经系统(CNS)感染的患者外,CSF HIV-RNA 在所有组中均与血浆 HIV-RNA 平行。HAD 患者的 CSF HIV-RNA 最高(中位数 [IQR]:4.73(3.84-5.35)log10 拷贝/ml)。在 972 名个体中有 126 名(13%)出现 CSF>血浆不匹配,且在各组之间存在差异,从原发性 HIV 中 1%,无症状组中 11%,到 HAD 患者中 30%。
本研究证实了之前在 HIV 疾病不同阶段 CSF HIV-RNA 变化的较小规模观察结果。总体而言,CSF 中的 HIV-RNA 比血浆低约 1 log10 拷贝/ml,但在相当一部分患者中发现了 CSF 不匹配,最常见于 HAD 患者,表明随着疾病进展,中枢神经系统的分隔程度增加。