Ulfhammer Gustaf, Yilmaz Aylin, Mellgren Åsa, Tyrberg Erika, Sörstedt Erik, Hagberg Lars, Gostner Johanna, Fuchs Dietmar, Zetterberg Henrik, Nilsson Staffan, Nyström Kristina, Edén Arvid, Gisslén Magnus
Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden.
J Infect Dis. 2025 Feb 20;231(2):e429-e437. doi: 10.1093/infdis/jiae555.
The incidence and clinical relevance of asymptomatic cerebrospinal fluid escape (CSFE) during antiretroviral therapy (ART) is uncertain. We examined the impact and incidence of asymptomatic CSFE in a Swedish HIV cohort.
Neuroasymptomatic people with HIV (PWH) who have been on ART for at least 6 months with suppressed plasma viral load were followed longitudinally. CSFE was defined as either increased CSF HIV-1 RNA with concurrent plasma suppression or CSF HIV-1 RNA exceeding that in plasma when both were quantifiable. Paired CSF and plasma were analyzed for HIV-1 RNA, neopterin, neurofilament light protein (NfL), white blood cell (WBC) count, and albumin ratio.
Asymptomatic CSFE (cutoff 50 copies/mL) was found in 4 of 173 PWH (2%) and 5 of 449 samples (1%). The corresponding proportions were 8% of PWH and 4% for samples using a 20 copies/mL cutoff for CSF HIV-1 RNA. CSFE samples (cutoff 20 copies/mL) had a 25% higher geometric mean of CSF neopterin (P = .01) and 8% higher albumin ratio (P = .04) compared to samples without CSFE. No differences were observed in CSF NfL levels (P = .8). The odds ratio for increased CSF WBC (≥ 3 cells/μL) in samples with CSFE was 3.9 (P = .004), compared to samples without elevated CSF viral load.
Asymptomatic CSFE was identified in only 4 (2%) PWH, with no cases of continuous CSFE observed. Increased CSF HIV-1 RNA was associated with biomarkers of CNS immune activation and blood-brain barrier impairment, but not with biomarkers of neuronal injury.
抗逆转录病毒疗法（ART）期间无症状脑脊液逸出（CSFE）的发生率及其临床相关性尚不确定。我们在一个瑞典HIV队列中研究了无症状CSFE的影响和发生率。
对接受ART至少6个月且血浆病毒载量被抑制的无症状HIV感染者（PWH）进行纵向随访。CSFE的定义为，在血浆病毒载量被抑制的同时脑脊液HIV-1 RNA增加，或者当两者均可定量时脑脊液HIV-1 RNA超过血浆中的水平。对配对的脑脊液和血浆进行HIV-1 RNA、新蝶呤、神经丝轻链蛋白（NfL）、白细胞（WBC）计数和白蛋白比率分析。
173例PWH中有4例（2%）以及449份样本中有5份（1%）发现无症状CSFE（临界值为50拷贝/毫升）。使用脑脊液HIV-1 RNA临界值为20拷贝/毫升时，相应的比例分别为PWH的8%和样本的4%。与无CSFE的样本相比，CSFE样本（临界值为20拷贝/毫升）的脑脊液新蝶呤几何平均值高25%（P = 0.01），白蛋白比率高8%（P = 0.04）。脑脊液NfL水平无差异（P = 0.8）。与脑脊液病毒载量未升高的样本相比，CSFE样本中脑脊液白细胞增加（≥ 3个细胞/微升）的优势比为3.9（P = 0.004）。
仅在4例（2%）PWH中发现无症状CSFE，未观察到持续CSFE病例。脑脊液HIV-1 RNA增加与中枢神经系统免疫激活和血脑屏障损伤的生物标志物相关，但与神经元损伤的生物标志物无关。
