一项前瞻性队列研究中，初治中国 HIV 感染患者中 efavirenz 400 mg 的药效动力学。
Pharmacodynamics of efavirenz 400 mg in treatment-naïve Chinese HIV-infected patients in a prospective cohort study.
机构信息
Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Department of Pharmacy and Pharmacology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
出版信息
BMC Infect Dis. 2021 Jan 23;21(1):112. doi: 10.1186/s12879-021-05802-8.
BACKGROUND
The plasma concentration of patients treated with efavirenz (EFV) 600 mg was found to exceed the upper limit of the proposed therapeutic window in most Chinese HIV-infected individuals; thus, dosage reduction of EFV to 400 mg daily warranted consideration. This study aimed to assess the pharmacodynamics of EFV 400 mg for HIV-1-infected patients in China.
METHOD
Twenty cART-naïve individuals were enrolled in this study. EFV 400 mg combined with tenofovir (TDF) and lamivudine (3TC) as an initial antiretroviral regimen was administered for 48 weeks. EFV concentration and T cell subsets as well as HIV RNA load were evaluated at baseline and at 4, 12, 24, and 48 weeks. Moreover, neuropsychiatric adverse effects were also assessed by the Hamilton depression (HAMD) scale and Pittsburgh sleep quality index (PSQI).
RESULTS
Eighteen males and two females whose median age was 26 (interquartile range [IQR]: 23-32) years completed 48 weeks of follow-up. The median EFV concentrations were 1.88 (IQR: 1.54-2.42), 1.74 (IQR: 1.36-1.93), 1.93 (IQR: 1.66-2.22), and 1.85 (IQR: 1.54-2.14) mg/L at weeks 4, 12, 24, and 48, respectively. The viral load was 4.59 (IQR: 4.10-5.19) log copies/mL at baseline, and it decreased by 4.6 (IQR: 3.98-5.18) log copies/mL from baseline to week 48. Three of 20 (15%), 10 of 20 (50.0%), 17 of 20 (85%), and 18 of 19 (95%) participants had a plasma viral load less than 50 copies/mL at weeks 4, 12, 24, and 48, respectively. The median CD4 cell count was 330 (IQR: 237-410) cells/μL at baseline, and it increased to 473 (IQR: 344-574) cells/μL at 48 weeks. The HAMD score was 5 (IQR: 3-9.8) and 3 (IQR: 2.25-4) at baseline and 48 weeks, respectively. The PSQI score was 4 (IQR: 2-5.8) and 3 (IQR: 2-4) at baseline and 48 weeks, respectively. Dizziness was the most common event, occurring in 70% of patients within the first 2 weeks of treatment.
CONCLUSION
Patients prescribed with EFV 400 mg-containing agents demonstrated favourable virological and immunological responses. And the plasma EFV concentration was within the recommended therapeutic range, with fewer adverse reactions than with EFV 600 mg. EFV 400 mg was effective and safe in Chinese HIV-infected patients.
TRIAL REGISTRATION
NCT04596488 ; Registered 21 October, 2020; Retrospectively registered.
背景
在中国，接受依非韦伦（EFV）600mg 治疗的患者的血浆浓度被发现超过了建议的治疗窗上限；因此，有必要考虑将 EFV 剂量减少至每日 400mg。本研究旨在评估 EFV 400mg 对中国 HIV-1 感染患者的药效学。
方法
本研究纳入了 20 名初治的接受含 EFV 的方案（EFV 400mg+替诺福韦（TDF）+拉米夫定（3TC））的 HIV 感染者。在基线、4、12、24 和 48 周时评估 EFV 浓度、T 细胞亚群和 HIV RNA 载量。此外，还通过汉密尔顿抑郁量表（HAMD）和匹兹堡睡眠质量指数（PSQI）评估神经精神不良事件。
结果
18 名男性和 2 名女性（中位年龄 26 岁，四分位距 [IQR]：23-32 岁）完成了 48 周的随访。EFV 浓度的中位数分别为 1.88（IQR：1.54-2.42）、1.74（IQR：1.36-1.93）、1.93（IQR：1.66-2.22）和 1.85（IQR：1.54-2.14）mg/L，分别在第 4、12、24 和 48 周时。基线时的病毒载量为 4.59（IQR：4.10-5.19）log 拷贝/mL，从基线到第 48 周下降了 4.6（IQR：3.98-5.18）log 拷贝/mL。20 名患者中，分别有 3 名（15%）、10 名（50.0%）、17 名（85%）和 18 名（95%）患者在第 4、12、24 和 48 周时的血浆病毒载量低于 50 拷贝/mL。基线时 CD4 细胞计数的中位数为 330（IQR：237-410）个/μL，在第 48 周时增加到 473（IQR：344-574）个/μL。基线和第 48 周时 HAMD 评分的中位数分别为 5（IQR：3-9.8）和 3（IQR：2.25-4）。基线和第 48 周时 PSQI 评分的中位数分别为 4（IQR：2-5.8）和 3（IQR：2-4）。头晕是最常见的事件，在治疗的前 2 周内，70%的患者出现了这种情况。
结论
接受 EFV 400mg 方案治疗的患者表现出良好的病毒学和免疫学应答。EFV 浓度在推荐的治疗范围内，不良反应少于 EFV 600mg。EFV 400mg 在中国 HIV 感染患者中是有效且安全的。
临床试验注册
NCT04596488；注册日期：2020 年 10 月 21 日；回顾性注册。
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