The aim of this study is to assess the effect of efavirenz exposure on neurocognitive functioning and investigate plasma neurofilament light (Nfl) as a biomarker for neurocognitive damage. Sub-analysis of the ESCAPE-study, a randomised controlled trial where virologically suppressed, cognitively asymptomatic HIV patients were randomised (2:1) to switch to rilpivirine or continue on efavirenz. At baseline and week 12, patients underwent an extensive neuropsychological assessment (NPA), and serum efavirenz concentration and plasma Nfl levels were measured. Subgroups of elevated (≥ 4.0 mg/L) and therapeutic (0.74 to< 4.0 mg/L) baseline efavirenz concentration were made. Differences between these groups in baseline NPA Z-scores and in delta scores after efavirenz discontinuation were assessed. Nfl level was measured using an ELISA analysis using single molecule array (Simoa) technology. Correlation of plasma NFL with NPA Z-scores was evaluated using a linear mixed model. The elevated group consisted of 6 patients and the therapeutic group of 48. At baseline, the elevated group showed lower composite Z-scores (median − 1.03; IQR 0.87 versus 0.27; 0.79. p 0.02). This effect was also seen on the subdomains verbal (p 0.01), executive functioning (p 0.02), attention (p < 0.01) and speed (p 0.01). In the switch group, the elevated group improved more on composite scores after discontinuing efavirenz (mean 0.58; SD 0.32 versus 0.22; 0.54, p 0.15). No association between plasma Nfl and composite Z-score was found. High efavirenz exposure is associated with worse cognitive functioning compared with patients with therapeutic concentrations. Plasma Nfl is not a suitable biomarker to measure cognitive damage in this group.

这项研究的目的是评估依非韦伦暴露对神经认知功能的影响，并研究血浆神经丝光（Nfl）作为神经认知损害​​的生物标志物。ESCAPE研究的亚分析是一项随机对照试验，在该研究中，被病毒抑制，无症状的HIV患者被随机分配（2：1），改用rilpivirine或继续依非韦伦治疗。在基线和第12周时，患者接受了广泛的神经心理学评估（NPA），并测量了血清依非韦伦浓度和血浆Nfl水平。进行了基线依非韦伦浓度升高（≥4.0 mg / L）和治疗性（0.74至<4.0 mg / L）亚组。评估了依法韦仑停药后，这些组之间的基线NPA Z得分和德尔塔评分的差异。使用单分子阵列（Simoa）技术的ELISA分析测量Nfl水平。使用线性混合模型评估血浆NFL与NPA Z评分的相关性。升高的组由6例患者组成，治疗组为48例。在基线时，升高的组显示较低的复合Z值（中位数-1.03； IQR 0.87对0.27； 0.79。p 0.02）。这种作用还体现在言语（p 0.01），执行功能（p 0.02），注意力（p  <0.01）和速度（p 0.01）的子域上。在转换组中，升高组在停用依非韦伦后，综合评分有更多改善（平均0.58； SD 0.32 vs 0.22； 0.54，p 0.15）。血浆Nfl和复合Z分数之间未发现关联。与具有治疗浓度的患者相比，高的依非韦伦暴露与较差的认知功能有关。血浆Nfl不是衡量该组认知损害的合适生物标志物。