Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
J Int AIDS Soc. 2022 Jan;25(1):e25862. doi: 10.1002/jia2.25862.
INTRODUCTION: Efavirenz (EFV) is commonly used for first-line antiretroviral therapy in children and adolescents with HIV, but is associated with neuropsychiatric and metabolic side effects. Rilpivirine (RPV) is better tolerated, and switching from EFV to RPV in virologically suppressed adults has been safe and efficacious, but data in adolescents are limited. Our primary objective was to describe the 48-week immunologic and virologic outcomes in virologically suppressed adolescents switching from EFV- to RPV-based antiretroviral therapy. Secondary objectives included assessment of neuropsychiatric adverse events, quality of life (QOL) and metabolic profiles while on RPV. METHODS: We conducted an open-label, single-arm, multi-centre study in Thailand in virologically suppressed adolescents aged 12-18 years receiving EFV plus two nucleoside/tide reverse transcriptase inhibitors (NRTIs/NtRTI) for ≥3 months. Participants were switched to an RPV (25 mg) tablet once daily, with the same NRTIs. HIV RNA viral load, CD4 cell count, fasting total cholesterol (TC), triglyceride, glucose, neuropsychiatric adverse events, depression and QOL were assessed over 48 weeks. Data were collected between February 2016 and September 2018. RESULTS: One hundred and two (52% male) adolescents were enrolled. Median age at entry was 15.5 years (IQR 14.4-17.0), median CD4 count was 664 cells/mm (29.9%); 58% were receiving tenofovir-DF and emtricitabine. At weeks 24 and 48, 96 (94.1%) and 94 (92.2%) participants were virologically suppressed, respectively, with no significant change in CD4 cell counts from baseline. Six (5.9%) participants experienced virologic failure, two of whom had RPV-associated mutations (K101E and Y181C) and a lamivudine-associated mutation (M184V/I). There were significant decreases in TC, triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) at weeks 24 and 48 and a significant increase in LDL/HDL ratio at week 48 compared to baseline. No substantial changes in EFV-related symptoms, depression score or health-related QOL were observed over time; however, there was significant improvement in performance-based assessments of executive function at week 24. CONCLUSIONS: A high proportion of adolescents (>92%) remained virologically suppressed up to 48 weeks after switching from EFV to RPV along with no significant change in CD4 cell counts. RPV was well tolerated and associated with improvements in metabolic profiles and executive function.
简介：依非韦伦（EFV）常用于儿童和青少年 HIV 感染者的一线抗逆转录病毒治疗，但与神经精神和代谢副作用相关。利匹韦林（RPV）的耐受性更好，在病毒学抑制的成年人中从 EFV 转换为 RPV 是安全有效的，但在青少年中的数据有限。我们的主要目标是描述病毒学抑制的青少年从 EFV 到基于 RPV 的抗逆转录病毒治疗转换后的 48 周免疫和病毒学结果。次要目标包括评估神经精神不良事件、接受 RPV 治疗时的生活质量（QOL）和代谢特征。
方法：我们在泰国进行了一项开放标签、单臂、多中心研究，纳入了接受 EFV 加两种核苷/核苷酸逆转录酶抑制剂（NRTI/NtRTI）治疗≥3 个月的病毒学抑制的 12-18 岁青少年。参与者转换为每日一次 RPV（25mg）片，同时使用相同的 NRTI。在 48 周时评估 HIV RNA 病毒载量、CD4 细胞计数、空腹总胆固醇（TC）、甘油三酯、葡萄糖、神经精神不良事件、抑郁和 QOL。数据收集于 2016 年 2 月至 2018 年 9 月。
结果：共纳入 102 名（52%为男性）青少年。入组时的中位年龄为 15.5 岁（IQR 14.4-17.0），中位 CD4 计数为 664 个细胞/mm³（29.9%）；58%接受替诺福韦地福辛酯和恩曲他滨治疗。在第 24 周和第 48 周，分别有 96（94.1%）和 94（92.2%）名参与者病毒学抑制，CD4 细胞计数与基线相比无显著变化。6 名（5.9%）参与者发生病毒学失败，其中 2 名发生与 RPV 相关的突变（K101E 和 Y181C）和与拉米夫定相关的突变（M184V/I）。与基线相比，第 24 周和第 48 周 TC、甘油三酯、高密度脂蛋白（HDL）和低密度脂蛋白（LDL）显著下降，第 48 周 LDL/HDL 比值显著升高。EFV 相关症状、抑郁评分或健康相关 QOL 随时间无明显变化；然而，执行功能的基于表现的评估在第 24 周有显著改善。
结论：从 EFV 转换为 RPV 后，超过 92%的青少年在 48 周内仍保持病毒学抑制，CD4 细胞计数无显著变化。RPV 耐受性良好，并与代谢特征和执行功能的改善相关。
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