Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Seville, Spain.
Antimicrob Agents Chemother. 2013 Aug;57(8):3746-51. doi: 10.1128/AAC.00315-13. Epub 2013 May 28.
There is significant intra- and intersubject variability in lopinavir (LPV) plasma concentrations after standard dosing; thus, this prospective study was conducted to determine whether low plasma LPV concentrations could be associated with virological outcome throughout lopinavir-ritonavir maintenance monotherapy (mtLPVr) in the clinical practice setting. If this hypothesis would be confirmed, LPV drug monitoring could improve the efficacy of mtLPVr regimens. Patients with previous virological failure (VF) on protease inhibitor-based regimens were also included if the genotypic resistance tests showed no major resistance mutation associated with reduced susceptibility to lopinavir-ritonavir. VF was defined as 2 consecutive determinations of HIV RNA levels of >200 copies/ml. Efficacy was analyzed by per-protocol analysis. Plasma LPV trough concentrations were measured by high-performance liquid chromatography using a UV detector. A total of 127 patients were included (22% with previous failure on protease inhibitors). After 96 weeks, the efficacy rate was 82.3% (95% confidence interval [CI(95)], 75.3 to 89.3%). Virological efficacy was independent of LPV plasma concentrations even when LPVr was given once daily. An adherence of <90% (HR, 4.4 [CI(95), 1.78 to 10.8; P = 0.001]) and the presence of blips in the preceding 12 months (HR, 3.06 [CI(95), 1.17 to 8.01; P = 0.022]) were the only variables independently associated with time to VF. These findings suggest that the LPV concentrations achieved with the standard doses of LPVr are sufficient to maintain virological control during monotherapy and that measurement of LPV concentrations is not useful for predicting virological outcome. Tight control of viral replication in the previous months and strict adherence throughout the mtLPVr regimen could improve the virological efficacy of this maintenance regimen.
在标准剂量给药后，洛匹那韦（LPV）的血浆浓度存在显著的个体内和个体间变异性；因此，本前瞻性研究旨在确定在洛匹那韦利托那韦维持单药治疗（mtLPVr）的临床实践环境中，低血浆 LPV 浓度是否与病毒学结果相关。如果这一假设得到证实，LPV 药物监测可以提高 mtLPVr 方案的疗效。如果基因型耐药检测显示没有与 LPV 利托那韦降低敏感性相关的主要耐药突变，也包括之前基于蛋白酶抑制剂方案治疗失败的患者。病毒学治疗失败（VF）定义为连续两次 HIV RNA 水平>200 拷贝/ml。疗效通过方案分析进行分析。采用高效液相色谱法（HPLC）结合紫外检测器（UV）检测 LPV 谷浓度。共纳入 127 例患者（22%曾因蛋白酶抑制剂治疗失败）。96 周后，疗效率为 82.3%（95%置信区间[CI95]，75.3 至 89.3%）。即使 LPVr 每日给药 1 次，病毒学疗效也与 LPV 血浆浓度无关。依从性<90%（HR，4.4[95%CI，1.78 至 10.8；P=0.001]）和前 12 个月内存在波动（HR，3.06[95%CI，1.17 至 8.01；P=0.022]）是与 VF 时间相关的唯一独立变量。这些发现表明，LPVr 标准剂量所达到的 LPV 浓度足以在单药治疗期间维持病毒学控制，并且 LPV 浓度的测量对于预测病毒学结果没有用处。在之前的几个月中严格控制病毒复制和严格遵循 mtLPVr 方案可以提高该维持方案的病毒学疗效。
