Background The incidence and clinical relevance of asymptomatic cerebrospinal fluid escape (CSF-E) during antiretroviral therapy (ART) is uncertain. We examined the impact and incidence of asymptomatic CSF-E in a Swedish HIV cohort. Methods Neuroasymptomatic people living with HIV (PLWH) who have been on ART for at least six months with suppressed plasma viral load were followed longitudinally. CSF-E was defined as either increased CSF HIV-1 RNA with concurrent plasma suppression or as 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. Results Asymptomatic CSF-E (cut-off 50 copies/mL) was found in 4/173 PLWH (2%) and 5/449 samples (1%). The corresponding proportions were 8% of PLWH and 4% for samples using a 20 copies/mL cut-off for CSF HIV-1 RNA. CSF-E samples (cut-off 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 CSF-E. No differences were observed in CSF NfL levels (P = .8). The odds ratio for increased CSF WBC (≥ 3 cells/μL) in samples with CSF-E was 3.9 (P = .004), compared to samples without elevated CSF viral load. Conclusion Asymptomatic CSF-E was identified in only four (2%) PLWH, with no cases of continuous CSF-E 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.

中文翻译：

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无症状脑脊液 HIV-1 逃逸：发生率和后果


背景 抗逆转录病毒治疗 （ART） 期间无症状脑脊液逃逸 （CSF-E） 的发生率和临床相关性尚不确定。我们检查了瑞典 HIV 队列中无症状 CSF-E 的影响和发生率。方法 纵向随访接受 ART 至少 6 个月且血浆病毒载量受抑制的神经无症状 HIV 感染者 （PLWH）。CSF-E 被定义为 CSF HIV-1 RNA 增加同时血浆抑制，或者当两者都可量化时，CSF HIV-1 RNA 超过血浆中的 CSF HIV-1 RNA。分析配对 CSF 和血浆的 HIV-1 RNA 、新蝶呤、神经丝轻蛋白 （NfL） 、白细胞 （WBC） 计数和白蛋白比值。结果 在 4/173 例 （2%） 和 5/449 例 （1%） 样本中发现无症状 CSF-E （临界值 50 拷贝/mL）。相应的比例为 PLWH 的 8%，使用 20 拷贝/mL CSF HIV-1 RNA 截留值的样品为 4%。与不含 CSF-E 的样品相比，CSF-E 样品 （截断 20 拷贝/mL） 的 CSF 新蝶呤几何平均值高 25% （P = .01），白蛋白比值高 8% （P = .04）。在 CSF NfL 水平中未观察到差异 （P = .8）。与没有升高的 CSF 病毒载量的样品相比，CSF-E 样品中 CSF WBC 增加 （≥ 3 个细胞/μL） 的比值比为 3.9 （P = .004）。结论 仅在 4 例 （2%） PLWH 中发现无症状 CSF-E，未观察到连续 CSF-E 病例。CSF HIV-1 RNA 增加与 CNS 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。