接受单一片剂与多片剂方案的 HIV 感染者中累积替诺福韦二磷酸酯暴露。
Cumulative tenofovir diphosphate exposure in persons with HIV taking single- vs. multiple-tablet regimens.
机构信息
Division of Infectious Diseases, School of Medicine, University of Colorado-AMC, Aurora, Colorado, USA.
Department of Biostatistics and Bioinformatics, Colorado School of Public Health, Aurora, Colorado, USA.
出版信息
Pharmacotherapy. 2022 Aug;42(8):641-650. doi: 10.1002/phar.2711. Epub 2022 Jun 24.
BACKGROUND
We assessed cumulative antiretroviral exposure-using tenofovir diphosphate (TFV-DP) in dried blood spots (DBS)-in persons with HIV (PWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) as single-tablet regimens (STR) or multiple-tablet regimens (MTR).
METHODS
Blood for DBS was prospectively collected in PWH on TDF during 1144 person visits (n = 523). Linear mixed-effects models, adjusted for baseline characteristics, were used to compare TFV-DP in STR versus MTR. Models adjusted for ART regimen using either anchor drug class, pharmacokinetic booster status (unboosted [u/] or boosted [b/]), or a combined STR/MTR and booster categorical variable.
RESULTS
In the anchor class-adjusted model, STR had 19% (95% confidence interval [CI]: 3%-37%; p = 0.02) higher TFV-DP concentrations than MTR. However, in the booster-adjusted model, STR was not significantly higher than MTR (estimate 5%, 95% CI: -9% to 21%; p = 0.48), although PWH on b/ART had 35% (95% CI: 16%-58%; p = 0.0001) higher TFV-DP than u/ART. In the STR/MTR-boosted variable model, when compared to u/MTR, b/STR, b/MTR, and u/STR had 25% (95% CI: 7%-47%; p = 0.005), 37% (95% CI: 17%-59%; p < 0.0001), and 7% (95% CI: -7% to 24%; p = 0.34) higher TFV-DP, respectively. Compared with b/MTR, b/STR had 9% (95% CI: -31% to 10%; p = 0.37) lower TFV-DP. In a sensitivity analysis of PWH with HIV viral load <20 copies/ml at all visits, b/STR and b/MTR had 34% (95% CI: 16%-55%; p < 0.0001) and 12% (95% CI: -2% to 27%; p = 0.09) higher TFV-DP, respectively, compared with u/MTR, while u/STR had 4% (95% CI: -15% to 8%; p = 0.50) lower TFV-DP. Compared with b/MTR, b/STR had 17% (95% CI: 2%-30%; p = 0.03) higher TFV-DP.
CONCLUSIONS
Persons with HIV on b/TDF-based ART had higher TFV-DP than u/ART, regardless of STR or MTR use. No significant differences in TFV-DP between regimens of the same boosting status (i.e., b/STR vs. b/MTR; u/STR vs. u/MTR) were observed in the full cohort. Future research should examine the clinical utility of these findings in patient-tailored ART selection.
背景
我们评估了接受替诺福韦酯（TDF）为基础的抗逆转录病毒治疗（ART）的 HIV 感染者（PWH）的累积抗逆转录病毒暴露情况-使用替诺福韦二磷酸（TFV-DP）在干血斑（DBS）中-接受替诺福韦二吡呋酯（TDF）的单一片剂方案（STR）或多片剂方案（MTR）。
方法
前瞻性收集了 1144 名接受 TDF 治疗的 PWH 在 523 次就诊时的 DBS 血样。使用线性混合效应模型，根据基线特征进行调整，比较 STR 与 MTR 的 TFV-DP。模型使用锚定药物类别、药代动力学增效剂状态（未增效[u/]或增效[b/]）或 STR/MTR 和增效剂分类变量调整 ART 方案。
结果
在锚定药物类别调整的模型中，STR 的 TFV-DP 浓度比 MTR 高 19%（95%置信区间[CI]：3%-37%；p=0.02）。然而，在增效剂调整的模型中，STR 与 MTR 无显著差异（估计值为 5%，95% CI：-9%-21%；p=0.48），尽管接受 b/ART 的 PWH 的 TFV-DP 比接受 u/ART 的 PWH 高 35%（95% CI：16%-58%；p=0.0001）。在 STR/MTR-增效剂变量模型中，与 u/MTR 相比，b/STR、b/MTR 和 u/STR 的 TFV-DP 分别高 25%（95% CI：7%-47%；p=0.005）、37%（95% CI：17%-59%；p < 0.0001）和 7%（95% CI：-7%至 24%；p=0.34）。与 b/MTR 相比，b/STR 的 TFV-DP 低 9%（95% CI：-31%至 10%；p=0.37）。在所有就诊时 HIV 病毒载量<20 拷贝/ml 的 PWH 的敏感性分析中，与 u/MTR 相比，b/STR 和 b/MTR 的 TFV-DP 分别高 34%（95% CI：16%-55%；p < 0.0001）和 12%（95% CI：-2%至 27%；p=0.09），而 u/STR 的 TFV-DP 低 4%（95% CI：-15%至 8%；p=0.50）。与 b/MTR 相比，b/STR 的 TFV-DP 高 17%（95% CI：2%-30%；p=0.03）。
结论
接受 b/TDF 为基础的 ART 的 HIV 感染者的 TFV-DP 比 u/ART 高，无论 STR 或 MTR 的使用情况如何。在整个队列中，同一增效剂状态（即 b/STR 与 b/MTR；u/STR 与 u/MTR）的方案之间没有观察到 TFV-DP 的显著差异。未来的研究应研究这些发现在患者个体化 ART 选择中的临床应用。
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