Background QUANTI-TAF aimed to establish tenofovir-diphosphate/emtricitabine-triphosphate (TFV-DP/FTC-TP) adherence benchmarks in dried blood spots (DBS) for persons with HIV (PWH) receiving tenofovir alafenamide/emtricitabine (TAF/FTC)-based antiretroviral therapy (ART). Methods During a 16-week pharmacokinetic study, PWH received TAF/FTC-based ART co-encapsulated with an ingestible sensor to directly measure cumulative (enrollment to final visit) and 10-day adherence. At monthly visits, intraerythrocytic concentrations of TAF/FTC anabolites (TFV-DP/FTC-TP) in DBS were quantified by LC-MS/MS and summarized at steady-state (week 12 or 16) as median (IQR). Linear mixed-effects models evaluated factors associated with TFV-DP/FTC-TP. Results 84 participants (86% male, 11% female, and 4% transgender), predominantly receiving bictegravir/TAF/FTC (73%) enrolled. 92% completed week 12 or 16 (94% receiving unboosted ART). TFV-DP for <85% (7/72), ≥85%-<95% (9/72), and ≥95% (56/72) cumulative adherence was 2696 (2039-4108), 3117 (2332-3339), and 3344 (2605-4293) fmol/punches. All participants with ≥85% cumulative adherence had TFV-DP ≥1800 fmol/punches. Adjusting for cumulative adherence, TFV-DP was higher with boosted ART, lower BMI, and in non-Blacks. FTC-TP for <85% (14/77), ≥85%-<95% (6/77), and ≥95% (57/77) 10-day adherence was 3.52 (2.64-4.48), 4.58 (4.39-5.06), and 4.96 (4.21-6.26) pmol/punches. All participants with ≥85% 10-day adherence had FTC-TP ≥2.5 pmol/punches. Low-level viremia (HIV-1 RNA ≥20-<200 copies/mL) occurred at 60/335 (18%) visits in 33/84 (39%) participants (range: 20-149 copies/mL), with similar TFV-DP (3177 [2494-4149] fmol/punches) compared with HIV-1 RNA <20 copies/mL visits (3279 [2580-4407] fmol/punches). Conclusions We propose PK-based TFV-DP (≥1800 fmol/punches)/FTC-TP (≥2.5 pmol/punches) benchmarks in DBS for PWH receiving unboosted TAF/FTC-based ART with ≥85% adherence. In the setting of high adherence, low-level viremia was common.

中文翻译：

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接受替诺福韦艾拉酚胺和恩曲他滨抗逆转录病毒治疗 (QUANTI-TAF) 的 HIV 感染者的干血斑依从性基准

背景 QUANTI-TAF 旨在为接受替诺福韦艾拉酚胺/恩曲他滨 (TAF/FTC) 治疗的 HIV 感染者 (PWH) 的干血斑 (DBS) 建立替诺福韦二磷酸盐/恩曲他滨三磷酸盐 (TFV-DP/FTC-TP) 依从性基准 -基于抗逆转录病毒治疗（ART）。方法 在一项为期 16 周的药代动力学研究中，PWH 接受了基于 TAF/FTC 的 ART，该 ART 与可摄入传感器共同封装，以直接测量累积（登记到最终就诊）和 10 天的依从性。每月访视时，通过 LC-MS/MS 定量 DBS 中 TAF/FTC 合成代谢物 (TFV-DP/FTC-TP) 的红细胞内浓度，并在稳态（第 12 或 16 周）时总结为中位数 (IQR)。线性混合效应模型评估了与 TFV-DP/FTC-TP 相关的因素。结果 84 名参与者（86% 为男性，11% 为女性，4% 为变性人），主要接受比克替拉韦/TAF/FTC (73%) 治疗。 92% 完成了第 12 或 16 周（94% 接受了未加强的 ART）。 <85% (7/72)、≥85%-<95% (9/72) 和 ≥95% (56/72) 的 TFV-DP 累积依从性为 2696 (2039-4108)、3117 (2332) -3339) 和 3344 (2605-4293) fmol/拳。所有累积依从性≥85% 的参与者的 TFV-DP ≥1800 fmol/拳。调整累积依从性后，在 ART 加强、BMI 较低和非黑人中，TFV-DP 较高。 ＜85% (14/77)、≥85%-＜95% (6/77) 和 ≥95% (57/77) 10 天依从性的 FTC-TP 为 3.52 (2.64-4.48)、4.58 (4.39-5.06) 和 4.96 (4.21-6.26) pmol/拳。所有 10 天依从性≥85% 的参与者的 FTC-TP ≥2.5 pmol/次。 33/84 (39%) 名参与者（范围：20-149 拷贝/mL）在 60/335 (18%) 次就诊时出现低水平病毒血症（HIV-1 RNA ≥20-<200 拷贝/mL），与 HIV-1 RNA <20 拷贝/mL 就诊（3279 [2580-4407] fmol/打孔）相比，TFV-DP 相似（3177 [2494-4149] fmol/打孔）。结论 我们提出了基于 PK 的 TFV-DP（≥1800 fmol/次）/FTC-TP（≥2.5 pmol/次）DBS 基准，用于接受未加强的基于 TAF/FTC 的 ART 的 PWH，且依从性≥85%。在高依从性的情况下，低水平病毒血症很常见。