EA 3620 Université Paris Descartes, Paris, France.
Antimicrob Agents Chemother. 2011 Sep;55(9):4320-5. doi: 10.1128/AAC.00166-11. Epub 2011 Jul 11.
Lopinavir-ritonavir (LPV/r) is a protease inhibitor that is used twice daily (BID) in the treatment of HIV infection in children. In the context of a single-center observational study, a switch to a once-a-day (QD) LPV/r regimen was proposed for considerations of convenience and to support adherence. The aims of this study were to compare the pharmacokinetics, viral loads, percentages of CD4(+) T cells, and lipid profiles after switching from a twice-daily to a once-daily regimen of LPV/r in experienced children. For this purpose, LPV concentrations, viral loads, CD4(+) T cells, and biochemistry data were measured in routine therapeutic drug monitoring procedures in 45 children and adolescents. Thirty-six children were switched to the QD regimen. Nine children on the BID or QD regimen were added for pharmacokinetic-study purposes only. The QD trough concentrations (C(trough)) of lopinavir in plasma were significantly lower than those observed with the BID regimen (P < 0.0001), but the 24-h exposure levels were not significantly lower with the QD than with the BID regimen (P = 0.09). Among 34 evaluable patients who switched from the BID to the QD regimen, the virological efficacy of LPV/r appeared to differ (P < 0.001), with 74% and 57% of viral loads, respectively, being <50 copies/ml (mean follow-up times, 33 and 20 months). Among 22 patients with stable virological control before the switch, 12 experienced either failure or blip (one observation of detectable viral load between two observations of undetectable viral load) after the switch. The change from the BID to the QD regimen did not result in significant differences in CD4(+) T cell percentages or total cholesterol, high-density lipoprotein (HDL) cholesterol, or triglyceride levels. The switch from the BID to the QD LPV/r regimen led to equivalent exposure and lower C(trough) values and resulted in lower levels of virological control in these antiretroviral-experienced children.
洛匹那韦利托那韦（LPV/r）是一种蛋白酶抑制剂，在儿童 HIV 感染的治疗中每天使用两次（BID）。在一项单中心观察性研究中，出于方便和支持依从性的考虑，提出将 LPV/r 的每日一次（QD）方案转换。本研究的目的是比较在有经验的儿童中从每日两次方案转换为每日一次方案后，洛匹那韦的药代动力学、病毒载量、CD4+T 细胞百分比和血脂谱。为此，在 45 名儿童和青少年的常规治疗药物监测程序中测量 LPV/r 每日两次与每日一次方案的 LPV 浓度、病毒载量、CD4+T 细胞和生物化学数据。36 名儿童转换为 QD 方案。仅出于药代动力学研究目的，9 名接受 BID 或 QD 方案的儿童被纳入研究。LPV 血浆谷浓度（C(trough)) 在 QD 方案中明显低于 BID 方案（P < 0.0001），但 24 小时暴露水平在 QD 方案中与 BID 方案相比没有明显降低（P = 0.09）。在 34 名从 BID 方案转换为 QD 方案的可评估患者中，LPV/r 的病毒学疗效似乎不同（P < 0.001），分别有 74%和 57%的病毒载量<50 拷贝/ml（平均随访时间分别为 33 个月和 20 个月）。在转换前病毒学控制稳定的 22 名患者中，12 名在转换后出现失败或短暂回升（两次不可检测的病毒载量之间观察到一次可检测的病毒载量）。从 BID 方案转换为 QD 方案不会导致 CD4+T 细胞百分比或总胆固醇、高密度脂蛋白（HDL）胆固醇或甘油三酯水平的显著差异。从 BID 方案转换为 QD LPV/r 方案导致等效暴露和更低的 C(trough)值，并导致这些抗逆转录病毒经验丰富的儿童病毒学控制水平降低。
