Jantarabenjakul Watsamon, Anugulruengkitt Suvaporn, Kasipong Naruporn, Thammajaruk Narukjaporn, Sophonphan Jiratchaya, Bunupuradah Torsak, Cressey Tim R, Colbers Angela, Burger David M, Phongsamart Wanatpreeya, Puthanakit Thanyawee, Pancharoen Chitsanu
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Research Unit in Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Antivir Ther. 2018;23(3):259-265. doi: 10.3851/IMP3198.
Rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor drug, could be a favourable drug for maintenance therapy in HIV-infected adolescents because it has few long-term side effects. However, data among adolescents switching from efavirenz (EFV) to RPV are limited. This study investigated the pharmacokinetics (PK), safety and efficacy of RPV in virologically suppressed HIV-1-infected adolescents after switching from EFV.
Adolescents aged 12-18 years on EFV-based antiretroviral therapy (ART) were switched from EFV to RPV (25 mg, once daily). Intensive 24-h blood samplings at 0 (pre-dose), 1, 2, 4, 5, 6, 9, 12 and 24 h were performed 4 weeks after switching. PK parameters were calculated using a non-compartmental method and compared with published data from the PAINT and pooled ECHO/THRIVE substudies. HIV RNA level was measured at weeks 12 and 24. Biochemical profiles were measured at baseline and week 24.
From January to June 2016, 20 adolescents (12 male) were enrolled. Median (IQR) age was 16 (15-17) years and weight was 49 (42-59) kg. Mean (sd) AUC, C and C of RPV were 2,041 (745) ng•h/ml, 69 (29) ng/ml and 143 (65) ng/ml, respectively. Median (IQR) T was 5 (2-9) h. Four adolescents had C <40 ng/ml. All PK parameters were comparable with published data. All adolescents remained virologically suppressed at week 24. Significant decreases in fasting total cholesterol, triglyceride and low-density lipoprotein were observed (P-value <0.05).
Virologically suppressed HIV-infected adolescents had adequate RPV exposure and remained virologically suppressed after switching from EFV. RPV can be used as long-term maintenance ART in HIV-infected adolescents.
利匹韦林（RPV）是一种非核苷类逆转录酶抑制剂药物，因其长期副作用较少，可能是用于HIV感染青少年维持治疗的理想药物。然而，从依非韦伦（EFV）转换为RPV的青少年中的相关数据有限。本研究调查了从EFV转换后，RPV在病毒学抑制的HIV-1感染青少年中的药代动力学（PK）、安全性和疗效。
接受基于EFV的抗逆转录病毒治疗（ART）的12至18岁青少年从EFV转换为RPV（25mg，每日一次）。转换后4周，在0（给药前）、1、2、4、5、6、9、12和24小时进行密集的24小时血液采样。使用非房室方法计算PK参数，并与PAINT以及汇总的ECHO/THRIVE子研究中的已发表数据进行比较。在第12周和第24周测量HIV RNA水平。在基线和第24周测量生化指标。
2016年1月至6月，招募了20名青少年（12名男性）。中位（IQR）年龄为16（15-17）岁，体重为49（42-59）kg。RPV的平均（标准差）AUC、Cmax和Cmin分别为2041（745）ng•h/ml、69（29）ng/ml和143（65）ng/ml。中位（IQR）Tmax为5（2-9）小时。4名青少年的Cmin<40 ng/ml。所有PK参数与已发表数据相当。所有青少年在第24周时仍处于病毒学抑制状态。观察到空腹总胆固醇、甘油三酯和低密度脂蛋白显著降低（P值<0.05）。
病毒学抑制的HIV感染青少年有足够的RPV暴露量，从EFV转换后仍保持病毒学抑制状态。RPV可作为HIV感染青少年的长期维持ART药物。
