Department of Infectious Diseases, Tianjin Second People's Hospital, Tianjin 300192, China.
Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
Chin Med J (Engl). 2021 Oct 13;134(23):2850-2856. doi: 10.1097/CM9.0000000000001824.
Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants' neuropsychiatric toxicity symptoms in a real-life setting.
A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch.
One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF (P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable.
The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.
接受依非韦伦（EFV）治疗的人类免疫缺陷病毒（HIV）感染者中枢神经系统（CNS）症状可能持续存在，并影响其生活质量。我们评估了依非韦伦不耐受者替代方案——艾维雷韦/考比司他/恩曲他滨/替诺福韦艾拉酚胺（E/C/F/TAF）的疗效，该方案是一种有效的治疗方法。具体来说，我们在真实环境中评估了 E/C/F/TAF 的安全性和疗效及其对参与者神经精神毒性症状的影响。
对正在接受 EFV 为基础方案治疗且持续存在 2 级及以上中枢神经系统毒性的病毒学抑制 HIV 阳性参与者进行前瞻性队列研究。将参与者转换为单一片剂联合方案 E/C/F/TAF，并随访 48 周。使用 CNS 副作用问卷、医院焦虑抑郁量表和匹兹堡睡眠质量指数来测量神经精神毒性症状。主要终点是在 EFV 停药后 12、24 和 48 周时，出现 2 级或更高中枢神经系统毒性的参与者比例。次要终点包括病毒学和免疫学反应以及 EFV 停药 48 周后对空腹血脂的影响。
本研究共纳入 196 名参与者（96.9%为男性，中位年龄为 37.5 岁，中位 EFV 治疗时间为 3.7 年）。转换为 E/C/F/TAF 后 12、24 和 48 周时，焦虑和睡眠障碍症状显著改善（P<0.05）。抑郁症状评分无显著变化。转换后 48 周时，所有参与者的 HIV 病毒载量均保持在<50 拷贝/ml，中位空腹血脂水平中度升高（总胆固醇[TC]：8.2mg/dL，低密度脂蛋白胆固醇[LDL-C]：8.5mg/dL，高密度脂蛋白胆固醇[HDL-C]：2.9mg/dL，甘油三酯[TG]：1.6mg/dL，TC/HDL-C 比值保持稳定。
E/C/F/TAF 单一片剂联合方案安全且耐受良好。本研究表明，EFV 转换为 E/C/F/TAF 可显著降低 2 级或更高中枢神经系统不良反应的 HIV 感染者的神经精神毒性症状。
