The Rotunda Hospital, Dublin, Ireland.
HIV Med. 2011 Mar;12(3):166-73. doi: 10.1111/j.1468-1293.2010.00865.x. Epub 2010 Aug 18.
The aim of the study was to determine total and unbound lopinavir (LPV) plasma concentrations in HIV-infected pregnant women receiving lopinavir/ritonavir (LPV/r tablet) undergoing therapeutic drug monitoring (TDM) during pregnancy and postpartum.
Women were enrolled in the study who were receiving the LPV/r tablet as part of their routine prenatal care. Demographic and clinical data were collected and LPV plasma (total) and ultrafiltrate (unbound) concentrations were determined in the first, second and third trimesters using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Postpartum sampling was performed where applicable. Antepartum and postpartum trough concentrations (C(trough) ) were compared independently [using analysis of variance (anova)] and on a longitudinal basis (using a paired t-test).
Forty-six women were enrolled in the study (38 Black African). Forty women initiated LPV/r treatment in pregnancy. Median (range) gestation at initiation was 25 (15-36) weeks and median (range) baseline CD4 count and viral load were 346 (14-836) cells/μL and 8724 (<50-267408) HIV-1 RNA copies/mL, respectively. Forty women (87%) had LPV concentrations above the accepted minimum effective concentration for wild-type virus (MEC; 1000 ng/mL). Geometric mean (95% confidence interval [CI]) total LPV concentrations in the first/second [3525 (2823-4227) ng/mL; n=16] and third [3346 (2813-3880) ng/mL; n=43] trimesters were significantly lower relative to postpartum [5136 (3693-6579) ng/mL; n=12] (P=0.006). In a paired analysis (n=12), LPV concentrations were reduced in the third trimester [3657 (2851-4463) ng/mL] vs. postpartum (P=0.021). No significant differences were observed in the LPV fraction unbound (fu%). Conclusions The above target concentrations achieved in the majority of women and similarities in the fu% suggest standard dosing of the LPV/r tablet is appropriate during pregnancy. However, reduced LPV concentrations in the second/third trimesters and potentially compromised adherence highlight the need for TDM-guided dose adjustment in certain cases.
本研究旨在确定接受洛匹那韦/利托那韦（LPV/r 片）治疗并进行治疗药物监测（TDM）的 HIV 感染孕妇在妊娠和产后的总洛匹那韦（LPV）和游离洛匹那韦（LPV）血浆浓度。
本研究纳入了正在接受 LPV/r 片作为常规产前护理一部分的孕妇。收集人口统计学和临床数据，并使用高效液相色谱-串联质谱法（HPLC-MS/MS）在妊娠第一、第二和第三 trimester 测定 LPV 血浆（总）和超滤（游离）浓度。如有必要，进行产后采样。采用方差分析（anova）和配对 t 检验分别对产前和产后谷浓度（C(trough)）进行比较。
本研究共纳入 46 名女性（38 名黑非洲人）。40 名女性在妊娠期间开始 LPV/r 治疗。起始妊娠时的中位（范围）孕周为 25（15-36）周，中位（范围）基线 CD4 计数和病毒载量分别为 346（14-836）个/μL 和 8724（<50-267408）HIV-1 RNA 拷贝/mL。40 名女性（87%）的 LPV 浓度高于野生型病毒的最低有效浓度（MEC；1000ng/mL）。第一/第二 trimester[3525（2823-4227）ng/mL；n=16]和第三 trimester[3346（2813-3880）ng/mL；n=43]的总 LPV 浓度的几何均数（95%置信区间[CI]）明显低于产后[5136（3693-6579）ng/mL；n=12]（P=0.006）。在配对分析（n=12）中，第三 trimester[3657（2851-4463）ng/mL]的 LPV 浓度较产后降低（P=0.021）。游离分数（fu%）无明显差异。结论：大多数女性达到了上述目标浓度，并且 fu%相似，提示 LPV/r 片在妊娠期间的标准剂量是合适的。然而，第二/第三 trimester LPV 浓度降低和潜在的药物依从性下降提示在某些情况下需要 TDM 指导剂量调整。
