评估多替拉韦/阿巴卡韦/拉米夫定神经毒性及其转换为埃替格韦/考比司他/恩曲他滨/替诺福韦艾拉酚胺后的可逆性的随机试验：GESIDA 9016
Randomized Trial Evaluating the Neurotoxicity of Dolutegravir/Abacavir/Lamivudine and Its Reversibility After Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide: GESIDA 9016.
作者信息
Perez Valero Ignacio, Cabello Alfonso, Ryan Pablo, De La Fuente-Moral Sara, Santos Ignacio, Vivancos Maria Jesus, Gonzalez Alicia, Gorgolas Miguel, Cuevas Guillermo, Diaz De Santiago Alberto, Cano Joanna, Rua Guadalupe, Yllescas Maria, González García Juan Julian
机构信息
Hospital Universitario La Paz, Madrid, Spain.
Fundación Jiménez Díaz, Madrid, Spain.
出版信息
Open Forum Infect Dis. 2020 Oct 18;7(12):ofaa482. doi: 10.1093/ofid/ofaa482. eCollection 2020 Dec.
BACKGROUND
Despite evidence shown of dolutegravir (DTG)-related neurotoxicity, which may be more common when combined with abacavir (ABC), its reversibility has not been explored in a clinical trial.
METHODS
We conducted a randomized, multicenter, open-label, pilot trial to evaluate the reversibility of patient-reported neuropsychiatric symptoms, developed or worsened on DTG/ABC/lamivudine (DTG/ABC/3TC), in virologically suppressed patients switched to cobicistat-boosted-elvitegravir/emtricitabine/tenofovir-alafenamide (EVG/COBI/FTC/TAF). Participants were randomized to immediate switch (baseline) or to defer switch (week 4), and then all completed 24 weeks of follow up on EVG/COBI/FTC/TAF. At each visit, participants completed Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression (HAD) scales and were interviewed about 11 neuropsychiatric symptoms potentially related with DTG through a questionnaire. At baseline and at the end of follow up, they also performed neurocognitive testing. Our primary objective was to compare changes in neuropsychiatric symptoms and PSQI and HAD scales between arms at week 4. Secondary objectives were to evaluate changes in neuropsychiatric symptoms and PSQI and HAD scales at weeks 4, 12, and 24 after switching to EVG/COBI/FTC/TAF and in neurocognitive performance and magnetic resonance imaging biomarkers at end of follow up.
RESULTS
Thirty-eight participants were included. Study arms were similar at baseline. At week 4, neuropsychiatric symptoms and PSQI and HAD scores remained unchanged in participants receiving DTG/ABC/3TC and improved significantly in participants receiving EVG/COBI/FTC/TAF. These significant improvements were also observed at weeks 4, 12, and 24 after all participants switched to EVG/COBI/FTC/TAF. In addition, global neurocognitive performance improved (NPZ-7) after switching to EVG/COBI/FTC/TAF.
CONCLUSIONS
Neuropsychiatric symptoms in patients on DTG/ABC/3TC could resolve or improve after switching to EVG/COBI/FTC/TAF.
背景
尽管有证据表明多替拉韦（DTG）相关的神经毒性，尤其是与阿巴卡韦（ABC）联用时可能更常见，但尚未在临床试验中探讨其可逆性。
方法
我们进行了一项随机、多中心、开放标签的试点试验，以评估在病毒学抑制的患者中，从DTG/ABC/拉米夫定（DTG/ABC/3TC）转换为考比司他增强的埃替格韦/恩曲他滨/替诺福韦艾拉酚胺（EVG/COBI/FTC/TAF）后，患者报告的神经精神症状（这些症状在DTG/ABC/3TC治疗时出现或加重）的可逆性。参与者被随机分为立即转换组（基线）或延迟转换组（第4周），然后所有参与者均完成了24周的EVG/COBI/FTC/TAF随访。每次访视时，参与者完成匹兹堡睡眠质量指数（PSQI）和医院焦虑抑郁量表（HAD），并通过问卷就11种可能与DTG相关的神经精神症状接受访谈。在基线和随访结束时，他们还进行了神经认知测试。我们的主要目标是比较第4周时两组之间神经精神症状、PSQI和HAD量表的变化。次要目标是评估转换为EVG/COBI/FTC/TAF后第4周、12周和24周时神经精神症状、PSQI和HAD量表的变化，以及随访结束时神经认知表现和磁共振成像生物标志物的变化。
结果
纳入了38名参与者。各研究组在基线时相似。在第4周时，接受DTG/ABC/3TC的参与者的神经精神症状、PSQI和HAD评分保持不变，而接受EVG/COBI/FTC/TAF的参与者则显著改善。在所有参与者转换为EVG/COBI/FTC/TAF后的第4周、12周和24周也观察到了这些显著改善。此外，转换为EVG/COBI/FTC/TAF后总体神经认知表现有所改善（NPZ-7）。
结论
从DTG/ABC/3TC转换为EVG/COBI/FTC/TAF后，患者的神经精神症状可能会缓解或改善。
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