Malawi College of Medicine, Blantyre, Malawi
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Antimicrob Agents Chemother. 2018 Jun 26;62(7). doi: 10.1128/AAC.00412-18. Print 2018 Jul.
There are limited data on the pharmacokinetic and safety profiles of artesunate-amodiaquine in human immnunodeficiency virus-infected (HIV) individuals receiving antiretroviral therapy. In a two-step intensive sampling pharmacokinetic trial, we compared the area under the concentration-time curve from 0 to 28 days (AUC) of an active metabolite of amodiaquine, desethylamodiaquine, and treatment-emergent adverse events between antiretroviral therapy-naive HIV adults and those taking nevirapine and ritonavir-boosted lopinavir-based antiretroviral therapy. In step 1, malaria-uninfected adults ( = 6/arm) received half the standard adult treatment regimen of artesunate-amodiaquine. In step 2, another cohort ( = 25/arm) received the full regimen. In step 1, there were no safety signals or significant differences in desethylamodiaquine AUC among participants in the ritonavir-boosted lopinavir, nevirapine, and antiretroviral therapy-naive arms. In step 2, compared with those in the antiretroviral therapy-naive arm, participants in the ritonavir-boosted lopinavir arm had 51% lower desethylamodiaquine AUC, with the following geometric means (95% confidence intervals [CIs]): 23,822 (17,458 to 32,506) versus 48,617 (40,787 to 57,950) ng · h/ml ( < 0.001). No significant differences in AUC were observed between nevirapine and antiretroviral therapy-naive arms. Treatment-emergent transaminitis was higher in the nevirapine (20% [5/25]) than the antiretroviral therapy-naive (0.0% [0/25]) arm (risk difference, 20% [95% CI, 4.3 to 35.7]; = 0.018). The ritonavir-boosted lopinavir antiretroviral regimen was associated with reduced desethylamodiaquine exposure, which may compromise artesunate-amodiaquine's efficacy. Coadministration of nevirapine and artesunate-amodiaquine may be associated with hepatoxicity.
在接受抗逆转录病毒疗法的人类免疫缺陷病毒（HIV）感染者中，青蒿琥酯-阿莫地喹的药代动力学和安全性特征数据有限。在一项两步强化采样药代动力学试验中，我们比较了抗逆转录病毒治疗初治 HIV 成人与接受奈韦拉平与利托那韦增强洛匹那韦为基础的抗逆转录病毒治疗的患者之间，阿莫地喹的一种活性代谢物去乙基阿莫地喹的 0 至 28 天（AUC）浓度-时间曲线下面积（AUC）和治疗中出现的不良事件。在第 1 步中，未感染疟疾的成年人（每组 6 人）接受青蒿琥酯-阿莫地喹的半标准成人治疗方案。在第 2 步中，另一队列（每组 25 人）接受完整的方案。在第 1 步中，在利托那韦增强洛匹那韦、奈韦拉平和抗逆转录病毒治疗初治组的参与者中，去乙基阿莫地喹 AUC 没有安全性信号或显著差异。在第 2 步中，与抗逆转录病毒治疗初治组相比，利托那韦增强洛匹那韦组的去乙基阿莫地喹 AUC 降低了 51%，以下为几何均值（95%置信区间[CI]）：23822（17458 至 32506）比 48617（40787 至 57950）ng·h/ml（<0.001）。奈韦拉平与抗逆转录病毒治疗初治组之间 AUC 无显著差异。奈韦拉平组（20%[25/125]）的治疗中出现转氨基酶升高高于抗逆转录病毒治疗初治组（0.0%[0/125]）（风险差异，20%[95%CI，4.3 至 35.7]；=0.018）。利托那韦增强洛匹那韦抗逆转录病毒方案与去乙基阿莫地喹暴露减少相关，这可能会影响青蒿琥酯-阿莫地喹的疗效。奈韦拉平与青蒿琥酯-阿莫地喹合用可能与肝毒性有关。
