Emtricitabine-Triphosphate in Dried Blood Spots as a Marker of Recent Dosing
Emtricitabine-Triphosphate in Dried Blood Spots as a Marker of Recent Dosing
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DOI：
10.1128/aac.01017-16
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发表时间：
2016-11-01
影响因子：
4.9
通讯作者：
Anderson, Peter L.
中科院分区：
文献类型：
--
作者：
Castillo-Mancilla, Jose;Seifert, Sharon;Anderson, Peter L.
需要采取新的客观措施来衡量坚持抗逆转录病毒治疗的情况。我们确定了干血斑（DBS）中的恩曲他滨三磷酸盐（FTC-TP）是否可用作最近使用替诺福韦二异山梨酯-恩曲他滨（TDF-FTC）的标记物。在从HIV阴性和HIV感染受试者中的共配制TDF-FTC的密集药代动力学（PK）研究中获得的DBS样本中估计FTC-TP的半衰期。DBS中可定量FTC-TP与血浆中替诺福韦（TFV）/FTC的一致性通过使用来自2项大型暴露前预防（PrEP）开放标签试验参与者的配对血浆DBS样本进行评价。使用DBS评价TDF-FTC给药后至FTC-TP不可检测的时间，该DBS来自入组TDF-FTC依从性可变的直接观察治疗研究的HIV阴性受试者。PK研究中FTC-TP的平均（95%置信区间[CI]）终末半衰期为35（23 - 47）h。在TDF-FTC给药后0至48小时获得的163个样本中，共有143个样本（88%）在DBS中具有可定量的FTC-TP，而在给药后> 48和> 96小时获得的样本分别为2/93（2%）和0/87（0%）。在入组PrEP试验的445名受试者的746份配对血浆DBS样本中，当血浆中的TFV/FTC均低于定量限时，98.9%的样本中也有FTC-TP，当血浆中的TFV或FTC可定量时，90.5%的样本中也有FTC-TP。DBS中FTC-TP的半衰期相对于TFV-二磷酸盐（TFV-DP）的半衰期较短，使其成为血浆中TFV-FTC检测的替代品。FTC-TP可以在DBS中与TFV-DP同时定量，TFV-DP定量TDF-FTC的累积依从性。(The本文中讨论的临床试验已在ClinicalTrials注册。gov，标识符为NCT 01040091、NCT 02022657、NCT 00458393、NCT 01772823和NCT 02012621）。
New objective measures of antiretroviral adherence are needed. We determined if emtricitabine triphosphate (FTC-TP) in dried blood spots (DBS) can be used as a marker of recent dosing with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC). The half-life of FTC-TP was estimated in DBS samples obtained from an intensive pharmacokinetic (PK) study of coformulated TDF-FTC in HIV-negative and HIV-infected participants. The concordance of quantifiable FTC-TP in DBS with tenofovir (TFV)/FTC in plasma was evaluated by utilizing paired plasma-DBS samples from participants enrolled in 2 large preexposure prophylaxis (PrEP) open-label trials. The time to FTC-TP nondetectability after TDF-FTC dosing was evaluated utilizing DBS from HIV-negative participants enrolled in a directly observed therapy study of variable adherence to TDF-FTC. The mean (95% confidence interval [CI]) terminal half-life of FTC-TP in the PK study was 35 (23 to 47) h. A total of 143/163 (88%) samples obtained 0 to 48 h post-TDF-FTC dose had quantifiable FTC-TP in DBS, compared with 2/93 (2%) and 0/87 (0%) obtained > 48 and > 96 h postdose. In 746 paired plasma-DBS samples from 445 participants enrolled in PrEP trials, when both TFV/FTC in plasma were below the limit of quantification, FTC-TP was as well in 98.9% of the samples, and when either TFV or FTC in plasma was quantifiable, FTC-TP was as well in 90.5% of the samples. The half-life of FTC-TP in DBS is short relative to that of TFV-diphosphate (TFV-DP), making it a surrogate for TFV-FTC detection in plasma. FTC-TP can be quantified in DBS simultaneously with TFV-DP, which quantifies cumulative adherence to TDF-FTC. (The clinical trials discussed in this article have been registered at ClinicalTrials. gov under identifiers NCT01040091, NCT02022657, NCT00458393, NCT01772823, and NCT02012621.)