Tenofovir diphosphate and emtricitabine triphosphate concentrations in blood cells compared with isolated peripheral blood mononuclear cells: a new measure of antiretroviral adherence?
Tenofovir diphosphate and emtricitabine triphosphate concentrations in blood cells compared with isolated peripheral blood mononuclear cells: a new measure of antiretroviral adherence?
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与分离的外周血单核细胞相比，血细胞中的替诺福韦二磷酸盐和恩曲他滨三磷酸盐浓度：抗逆转录病毒依从性的新衡量标准？
DOI：
10.1097/qai.0b013e3182794723
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发表时间：
2013-03-01
期刊：
影响因子：
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通讯作者：
Kashuba AD
中科院分区：
文献类型：
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作者：
Adams JL;Sykes C;Menezes P;Prince HM;Patterson KB;Fransen K;Crucitti T;De Baetselier I;Van Damme L;Kashuba AD
替诺福韦（TFV）和恩曲他滨（FTC）在外周血单个核细胞（PBMC）中的活性代谢产物已被用作长期抗逆转录病毒（ARV）粘附的标志物。然而，分离PBMC的过程是昂贵的、复杂的，并且在许多情况下是不可行的。我们比较了全血离心后获得的上层压积细胞（ULPC）中的TFV-二磷酸（TFV-DP）和FTC-三磷酸（FTC-TP）浓度与分离的PBMC作为粘附的可能替代标志物。10名HIV RNA <50拷贝/mL的HIV+成人接受含TDF/FTC的方案，在6小时内提供了5份配对的PBMC和ULPC样本。通过液相色谱/质谱法（LC-MS/MS）分析TFV-DP和FTC-TP浓度。使用非房室方法计算部分曲线下面积（AUC），并确定PBMC和ULPC之间的斯皮尔曼秩相关性（rho）。PBMC中TFV-DP的中位（第25 - 75百分位数）浓度为143（103-248）fmol/106个细胞，ULPC中为227（160-394）fmol/106个细胞（rho=0.65;p <0.0001）。FTC-TP在PBMC中的浓度为6660（5650-10000）fmol/106个细胞，在ULPC中的浓度为19.0（12.0-27.8）fmol/106个细胞（rho 0.55;p<0.0001）。与PBMC相比，ULPC TFV-DP高64%，FTC-TP低99.7%。另外1例接受TDF/FTC单次给药的受试者中TFV-DP和FTC-TP的ULPC浓度分别仅为其他10例受试者的0.05%和25%。ULPC浓度与PBMC浓度显著相关。初步单次给药数据表明间歇性给药与持续性给药之间存在一定差异。TFV-DP和FTC-TP的ULPC浓度应作为ARV依从性的简单收集替代指标进行进一步研究。
The active metabolites of tenofovir (TFV) and emtricitabine (FTC) in peripheral blood mononuclear cells (PBMCs) have been used as markers of long-term antiretroviral (ARV) adherence. However, the process of isolating PBMCs is expensive, complex, and not feasible in many settings. We compared concentrations of TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP) in the upper layer packed cells (ULPC) obtained after whole blood centrifugation to isolated PBMCs as a possible alternative marker of adherence. Ten HIV+ adults with HIV RNA <50 copies/mL on a TDF/FTC-containing regimen provided five paired PBMC and ULPC samples over 6h. TFV-DP and FTC-TP concentrations were analyzed by liquid chromatography/mass spectrometry (LC-MS/MS). Partial areas under the curve (AUC) were calculated using noncompartmental methods and Spearman Rank Correlations (rho) between PBMC and ULPC were determined. The median (25th–75th percentile) concentration of TFV-DP in PBMCs was 143 (103-248) fmol/106 cells and in ULPC was 227 (160-394) fmol/106 cells (rho=0.65;p <0.0001). The concentration of FTC-TP in PBMCs was 6660 (5650-10000) fmol/106 cells and in ULPC was 19.0 (12.0-27.8) fmol/106 cells (rho 0.55;p<0.0001). Compared to PBMCs, ULPC TFV-DP was 64% higher and FTC-TP was 99.7% lower. ULPC concentrations of TFV-DP and FTC-TP in 1 additional subject receiving a single dose of TDF/FTC were only 0.05% and 25%, of the other 10 subjects, respectively. ULPC concentrations significantly correlated with PBMC concentrations. Preliminary single-dose data suggest some discrimination between intermittent vs. consistent dosing. ULPC concentrations of TFV-DP and FTC-TP should be further investigated as a simply-collected, surrogate measure of ARV adherence.