Shikuma Cecilia M, Kohorn Lindsay, Paul Robert, Chow Dominic C, Kallianpur Kalpana J, Walker Maegen, Souza Scott, Gangcuangco Louie Mar A, Nakamoto Beau K, Pien Francis D, Duerler Timothy, Castro Linda, Nagamine Lorna, Soll Bruce
a John A. Burns School of Medicine, University of Hawaii , Honolulu , Hawaii , USA.
b Missouri Institute of Mental Health, University of Missouri , St. Louis , MO , USA.
HIV Clin Trials. 2018 Aug;19(4):139-147. doi: 10.1080/15284336.2018.1511348. Epub 2018 Nov 19.
The antiretroviral drug efavirenz (EFV) has been linked to disordered sleep and cognitive abnormalities. We examined sleep and cognitive function and subsequent changes following switch to an alternative integrase inhibitor-based regimen. Thirty-two HIV-infected individuals on EFV, emtricitabine, and tenofovir (EFV/FTC/TDF) without traditional risk factors for obstructive sleep apnea (OSA) were randomized 2:1 to switch to elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/COBI/FTC/TDF) or to continue EFV/FTC/TDF therapy for 12 weeks. Overnight polysomnography and standardized sleep and neuropsychological assessments were performed at baseline and at 12 weeks. No significant differences in change over 12 weeks were noted between the two arms in any sleep or neuropsychological test parameter. At entry, however, the rate of sleep disordered breathing (SDB) was substantially higher in study subjects compared to published age-matched norms and resulted in a high assessed OSA rate of 59.4%. Respiratory Disturbance Index (RDI), a measure of SDB, correlated with age- and education-adjusted global neuropsychological Z-score (NPZ) (r = -0.35, p = 0.05). Sleep Maintenance Efficiency, Wake after Sleep Onset, REM Sleep and RDI correlated with domain-specific NPZ for learning and memory (all p-values ≤ 0.05). Among HIV-infected individuals on EFV-based therapy and without traditional risk factors for OSA, sleep and neuropsychological abnormalities do not readily reverse after discontinuation of EFV. High baseline rates of SDB and abnormalities in sleep architecture exist in this population correlating with neuropsychological impairment. The role of HIV immuno-virologic or lifestyle factors as contributing etiologies should be explored. OSA may be an under-recognized etiology for cognitive dysfunction during chronic HIV.
抗逆转录病毒药物依非韦伦(EFV)与睡眠紊乱和认知异常有关。我们研究了改用基于整合酶抑制剂的替代方案后的睡眠和认知功能及后续变化。32名接受EFV、恩曲他滨和替诺福韦(EFV/FTC/TDF)治疗且无阻塞性睡眠呼吸暂停(OSA)传统危险因素的HIV感染者,按2:1随机分组,分别改用埃替拉韦/考比司他/恩曲他滨/替诺福韦(EVG/COBI/FTC/TDF)或继续EFV/FTC/TDF治疗12周。在基线和12周时进行夜间多导睡眠图检查以及标准化的睡眠和神经心理学评估。在任何睡眠或神经心理学测试参数方面,两组在12周内的变化均无显著差异。然而,在入组时,与已发表的年龄匹配标准相比,研究对象的睡眠呼吸紊乱(SDB)发生率显著更高,导致评估的OSA发生率高达59.4%。呼吸紊乱指数(RDI)是SDB的一项指标,与年龄和教育程度调整后的总体神经心理学Z评分(NPZ)相关(r = -0.35,p = 0.05)。睡眠维持效率、睡眠起始后觉醒、快速眼动睡眠和RDI与学习和记忆的特定领域NPZ相关(所有p值≤0.05)。在接受基于EFV治疗且无OSA传统危险因素的HIV感染者中,停用EFV后睡眠和神经心理学异常不易逆转。该人群中SDB的基线发生率较高且睡眠结构存在异常,这与神经心理学损害相关。应探索HIV免疫病毒学或生活方式因素作为病因的作用。OSA可能是慢性HIV感染期间认知功能障碍的一个未被充分认识的病因。