Sufficient drug concentrations are required for efficacy of antiretroviral drugs used in HIV care and prevention. Measurement of nucleotide analogs, included in most HIV medication regimens, enables monitoring of short- and long-term adherence and the risk of treatment failure. The REverSe TRanscrIptase Chain Termination (RESTRICT) assay rapidly infers the concentration of intracellular nucleotide analogs based on the inhibition of DNA synthesis by HIV reverse transcriptase enzyme. Here, we introduce a probabilistic model for RESTRICT and demonstrate selective measurement of multiple nucleotide analogs using DNA templates designed according to the chemical structure of each drug. We measure clinically relevant concentrations of tenofovir diphosphate, emtricitabine triphosphate, lamivudine triphosphate, and azidothymidine triphosphate with agreement between experiment and theory. RESTRICT represents a new class of activity-based assays for therapeutic drug monitoring in HIV care and could be extended to other diseases treated with nucleotide analogs.

中文翻译：

---

反向转录酶链终止 (RESTRICT)，用于选择性测量 HIV 护理和预防中使用的核苷酸类似物


用于艾滋病毒护理和预防的抗逆转录病毒药物需要足够的药物浓度才能发挥作用。大多数艾滋病毒治疗方案中都包含核苷酸类似物的测量，可以监测短期和长期的依从性以及治疗失败的风险。 REverSe 转录酶链终止 (RESTRICT) 测定基于 HIV 逆转录酶对 DNA 合成的抑制，快速推断细胞内核苷酸类似物的浓度。在这里，我们介绍了 RESTRICT 的概率模型，并演示了使用根据每种药物的化学结构设计的 DNA 模板选择性测量多个核苷酸类似物。我们测量了替诺福韦二磷酸、恩曲他滨三磷酸、拉米夫定三磷酸和叠氮胸苷三磷酸的临床相关浓度，实验与理论一致。 RESTRICT 代表了一种新的基于活性的检测方法，用于 HIV 护理中的治疗药物监测，并且可以扩展到使用核苷酸类似物治疗的其他疾病。