The prevalence of neurocognitive impairment in people living with HIV is estimated between 30 and 50%. The pathogenesis of HIV-associated neurocognitive disorders is complex and multifactorial. Aim of the study was to measure the change in CSF biomarkers, Fibroscan and IMT measurements in PLWH with HAND randomized to a less neurotoxic regimen, or continuing their treatment. Adult patients with HAND were screened and enrolled if presenting no major resistance associated mutations, no HIV viral replication, not on efavirenz or darunavir, with R5-tropic HIV and without major confounding conditions. Lumbar puncture, IMT and Fibroscan measurements were performed. After 1:1 randomization to a less neurotoxic regimen consisting of darunavir/cobicistat plus emtricitabine plus maraviroc, or mantaining actual care, tests were repeated after 24 weeks: CSF biomarkes (HIV RNA, tau, p-tau, Beta-amyloid_1-42, S100Beta and neopterin) were included. Non-parametric tests (Mann–Whitney and Wilcoxon’s) were used. 28 participants completed the study. Male and European ancestry were prevalent; median age was 55 years (51–60). All patients were virally suppressed; median CD4 + count was 626 cell/uL (469–772). Baseline characteristics were similar between the study arms. A significant decrease in CSF p-tau and an increase in CSF neopterin and NFL were observed. We observed a significant reduction in liver stiffness at W24. Despite a small sample size we observed changes in neuromarkers and in hepatic stiffness in patients randomized to the experimental arm. We observed changes in CSF biomarkers (lower phosphorylated-tau and higher neopterin and NFL) that need to be replicated in large cohorts. Subclinical neurotoxicity may be observed in patients with HAND and warrants prospective studies.

Graphical Abstract

中文翻译：

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随机接受神经毒性较小治疗方案的 HIV 相关神经认知障碍患者脑脊液、肝脏和内膜中层厚度生物标志物的变化

HIV 感染者神经认知障碍的患病率估计在 30% 至 50% 之间。HIV 相关神经认知障碍的发病机制是复杂且多因素的。该研究的目的是测量 PLWH 中 CSF 生物标志物、Fibroscan 和 IMT 测量的变化，HAND 随机接受神经毒性较小的方案或继续治疗。如果没有出现重大耐药相关突变、没有 HIV 病毒复制、未服用依非韦伦或达芦那韦、患有 R5 倾向性 HIV 并且没有重大混杂条件，则对 HAND 成年患者进行筛查和入组。进行腰椎穿刺、IMT 和 Fibroscan 测量。按 1:1 随机分配至由达芦那韦/考比司他加恩曲他滨加马拉韦罗组成的神经毒性较小的方案，或维持实际护理后，24 周后重复测试：脑脊液生物标志物（HIV RNA、tau、p-tau、β-淀粉样蛋白 1-42 _）、S100Beta 和新蝶呤）均包含在内。使用非参数检验（Mann–Whitney 和 Wilcoxon 检验）。28 名参与者完成了这项研究。男性和欧洲血统很普遍；中位年龄为 55 岁 (51-60)。所有患者的病毒均受到抑制；CD4 + 计数中位数为 626 个细胞/uL (469-772)。研究组之间的基线特征相似。观察到脑脊液 p-tau 显着减少，脑脊液新蝶呤和 NFL 增加。我们观察到第 24 周肝脏硬度显着降低。尽管样本量很小，但我们观察到随机分配到实验组的患者神经标志物和肝硬度的变化。我们观察到脑脊液生物标志物（磷酸化 tau 蛋白降低、新蝶呤和 NFL 升高）的变化，需要在大型队列中进行复制。在 HAND 患者中可能会观察到亚临床神经毒性，值得进行前瞻性研究。

图形概要