Influence of efavirenz and 8-hydroxy-efavirenz plasma levels on cognition and central nervous system side effects

IF 2.8 3区医学 Q2 INFECTIOUS DISEASES

HIV Medicine Pub Date : 2023-12-17 DOI:10.1111/hiv.13600

Alice Ranzani, Francesco Castelli, Antonio Di Biagio, Antonella d'Arminio Monforte, Antonio D'Avolio, Alessandro Soria, Francesca Bai, Emanuele Focà, Lucia Taramasso, Andrea Calcagno, Elena Bresciani, Antonio Torsello, Paolo Bonfanti, Giuseppe Lapadula

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引用次数: 0

Abstract

Objectives

To investigate whether efavirenz (EFV) or 8-hydroxy-EFV (8-OH-EFV) plasma levels are associated with neurocognitive impairment and central nervous system (CNS) side effects.

Methods

We conducted a cross-sectional analysis to explore the potential links between EFV/8-OH-EFV levels and cognitive performance or CNS-related side effects in patients screened within a randomized trial involving a switch from EFV to rilpivirine. The Mann–Whitney test was employed to compare drug levels in patients with or without cognitive impairment, depression, anxiety, sleep disorder or CNS symptoms. Additionally, Spearman's test was used to assess correlations between drug levels and test scores.

Results

Among 104 patients, neither EFV nor 8-OH-EFV levels were linked to cognitive impairment, although trends towards higher EFV levels were observed in those with impaired executive function (p = 0.055) and language performances (p = 0.021). On the other hand, elevated 8-OH-EFV levels, but not EFV levels, were associated with more CNS side effects (222 vs. 151 ng/mL, p = 0.027), depressive symptoms (247 vs. 164 ng/mL, p = 0.067) and sleep impairment (247 vs. 164 ng/mL, p = 0.078). Consistently, a trend towards a correlation between EFV levels and lower z-scores in executive function and motor function was observed, while 8-OH-EFV levels, but not EFV levels, were directly correlated with symptom scores.

Conclusions

Higher levels of 8-OH-EFV were associated with CNS side effects, while EFV levels were only marginally associated with cognitive performance, thus suggesting that EFV and its metabolite may act differently in determining detrimental neurological effects.

查看原文本刊更多论文

依非韦伦和 8-羟基依非韦伦血浆水平对认知和中枢神经系统副作用的影响。

研究目的研究依非韦伦（EFV）或8-羟基-EFV（8-OH-EFV）血浆水平是否与神经认知障碍和中枢神经系统（CNS）副作用有关：我们进行了一项横断面分析，以探讨在一项随机试验中筛选出的从 EFV 转为利匹韦林的患者中，EFV/8-OH-EFV 水平与认知能力或中枢神经系统相关副作用之间的潜在联系。采用曼-惠特尼检验比较了有无认知障碍、抑郁、焦虑、睡眠障碍或中枢神经系统症状患者的药物水平。此外，还使用斯皮尔曼检验来评估药物水平与测试评分之间的相关性：在104名患者中，EFV和8-OH-EFV水平均与认知障碍无关，但在执行功能受损（p = 0.055）和语言表达能力受损（p = 0.021）的患者中观察到EFV水平升高的趋势。另一方面，8-OH-EFV 水平升高与更多的中枢神经系统副作用（222 vs. 151 ng/mL，p = 0.027）、抑郁症状（247 vs. 164 ng/mL，p = 0.067）和睡眠障碍（247 vs. 164 ng/mL，p = 0.078）有关，而与 EFV 水平无关。一致的是，EFV水平与执行功能和运动功能的较低z分数之间存在相关趋势，而8-OH-EFV水平（而非EFV水平）与症状分数直接相关：结论：8-OH-EFV水平较高与中枢神经系统副作用有关，而EFV水平与认知表现仅有微弱相关性，这表明EFV及其代谢物在决定对神经系统的有害影响方面可能作用不同。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

HIV Medicine 医学-传染病学

CiteScore

5.10

自引率

10.00%

发文量

167

审稿时长

6-12 weeks

期刊介绍： HIV Medicine aims to provide an alternative outlet for publication of international research papers in the field of HIV Medicine, embracing clinical, pharmocological, epidemiological, ethical, preclinical and in vitro studies. In addition, the journal will commission reviews and other feature articles. It will focus on evidence-based medicine as the mainstay of successful management of HIV and AIDS. The journal is specifically aimed at researchers and clinicians with responsibility for treating HIV seropositive patients.