It is debated whether CNS involvement begins during acute human immunodeficiency virus (HIV) infection in persons without meningitis/encephalitis and whether specific antiretroviral drugs or combinations would be beneficial. Neurologically asymptomatic participants enrolled in a randomized and controlled study comparing three combination antiretroviral regimens (tenofovir alafenamide/emtricitabine plus dolutegravir; darunavir; or both) during primary HIV infection were enrolled. Serum and CSF were collected at baseline and at 12 and 48 (serum only) weeks after treatment initiation. Single molecule array was used to measure neurofilament light chain (NFL), total tau protein (Tau), brain-derived neurotrophic factor, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase. We assessed the longitudinal change in biomarkers over time, in addition to the change in the prevalence of serum NFL concentrations above previously published age-adjusted cut-offs (7 pg/ml if 5–18 years, 10 pg/ml if 18–51 years, 15 pg/ml if 51–61 years, 20 pg/ml if 61–70 years and 35 pg/ml if >70 years). Serum was available from 47 participants at all time points, and CSF was available from 13 participants at baseline and 7 at Week 12. We observed a significant direct serum-to-CSF correlation for NFL (ρ = 0.692, P = 0.009), GFAP (ρ = 0.659, P = 0.014) and brain-derived neurotrophic factor (ρ = 0.587, P = 0.045). Serum (ρ = 0.560, P = 0.046) and CSF NFL (ρ = 0.582, P = 0.037) concentrations were directly associated with CSF HIV RNA levels. We observed a significant decrease over time in serum NFL (P = 0.006) and GFAP (P = 0.006) but not in the other biomarkers. No significant difference was observed among the treatment arms. At baseline, serum and CSF age-adjusted NFL levels were above age-adjusted cut-offs in 23 (48.9%) and four participants (30.8%), respectively; considering serum NFL, this proportion was lower at Weeks 12 (31.9%, P = 0.057) and 48 (27.7%, P = 0.13). A relevant proportion of neurologically asymptomatic participants had abnormal CSF and serum NFL levels during primary HIV infection. NFL and GFAP decreased in serum following combination antiretroviral therapy without significant differences among the treatment arms.

中文翻译：

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原发性 HIV 感染期间无症状患者的血清和 CSF 生物标志物：一项随机研究


对于无脑膜炎/脑炎的人群急性人类免疫缺陷病毒 （HIV） 感染是否开始受累，以及特异性抗逆转录病毒药物或联合治疗是否有益，存在争议。纳入了一项随机对照研究，比较了原发性 HIV 感染期间三种联合抗逆转录病毒方案（替诺福韦艾拉酚胺/恩曲他滨加多替拉韦;darunavir;或两者）的神经系统无症状参与者。在基线和治疗开始后 12 周和 48 周 （仅血清） 收集血清和 CSF。采用单分子芯片检测神经丝轻链 （NFL） 、总 tau 蛋白 （Tau ）、脑源性神经营养因子、胶质纤维酸性蛋白 （GFAP） 和泛素 C 端水解酶。我们评估了生物标志物随时间的纵向变化，以及血清 NFL 浓度患病率高于先前公布的年龄调整临界值的变化（5-18 岁为 7 pg/ml，18-51 岁为 10 pg/ml，51-61 岁为 15 pg/ml，61-70 岁为 20 pg/ml，>70 为 35 pg/ml）。在所有时间点有 47 名参与者提供血清，基线时有 13 名参与者提供 CSF，第 12 周时有 7 名参与者提供 CSF。我们观察到 NFL （ρ = 0.692，P = 0.009）、GFAP （ρ = 0.659，P = 0.014） 和脑源性神经营养因子 （ρ = 0.587，P = 0.045） 的显著直接血清与 CSF 相关性。血清 （ρ = 0.560，P = 0.046） 和 CSF NFL （ρ = 0.582，P = 0.037） 浓度与 CSF HIV RNA 水平直接相关。我们观察到血清 NFL （P = 0.006） 和 GFAP （P = 0.006） 随着时间的推移显着降低，但在其他生物标志物中没有。在治疗组之间未观察到显著差异。 在基线时，23 名 （48.9%） 和 4 名参与者 （30.8%） 的血清和 CSF 年龄调整后的 NFL 水平高于年龄调整的临界值;考虑到血清 NFL，该比例在第 12 周 （31.9%，P = 0.057） 和第 48 周 （27.7%，P = 0.13） 较低。在原发性 HIV 感染期间，相关比例的神经系统无症状参与者的 CSF 和血清 NFL 水平异常。联合抗逆转录病毒治疗后血清中的 NFL 和 GFAP 降低，治疗组之间没有显著差异。