*Aix-Marseille University, APHM Sainte-Marguerite, Service d'Immuno-Hématologie Clinique, INSERM U912 (SESSTIM), Marseille, France †Aix-Marseille University, APHM La Timone, Laboratoire de Pharmacocinétique et de Toxicologie, CRO2-INSERM, UMR911, Marseille, France ‡Département de Biostatistique et Informatique Médicale, Centre Hospitalo-Universitaire Sainte Marguerite, Marseille, France.
J Acquir Immune Defic Syndr. 2013 Apr 1;62(4):375-80. doi: 10.1097/QAI.0b013e31827ce4ee.
Tenofovir disoproxil fumarate (TDF) is known to induce renal dysfunction in HIV-infected patients. The aim of this retrospective study was to evaluate the correlation between TDF trough concentration (Ctrough-TDF) and glomerular filtration rate (GFR) in a cohort of patients on antiretroviral therapy.
A total of 163 patients with at least one determination of Ctrough-TDF between 17-24 hours were retrospectively selected from a computerized database and distributed into 3 groups defined by TDF concentrations <40 (11.7%), between 40 and 90 (36.8%), and >90 (high-level group, 51.5%) ng/mL. GFR was measured by Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration formulae at the times of TDF initiation and Ctrough-TDF determination and after 12 months.
At the time of Ctrough-TDF measurement, median duration of TDF-based therapy was 21.1 months. GFR was significantly decreased in high-level group (-8.5 mL/min; P < 0.001) whatever the method used. GFR decline was significantly associated with an older age. Gender-stratified analysis showed that the early impact of Ctrough-TDF >90 ng/mL was significant in women only. After 12 months, the decrease in GFR in patients with high Ctrough-TDF was observed in both men and women (-8.27; P = 0.003).
The high prevalence of elevated Ctrough-TDF and its correlation with an increased risk of renal impairment support the usefulness of therapeutic drug monitoring for TDF, particularly in women and older patients.
富马酸替诺福韦二吡呋酯（TDF）已知可导致 HIV 感染患者肾功能障碍。本回顾性研究旨在评估接受抗逆转录病毒治疗的患者队列中 TDF 谷浓度（Ctrough-TDF）与肾小球滤过率（GFR）之间的相关性。
从计算机数据库中回顾性选择了至少有一次 17-24 小时 Ctrough-TDF 测定的 163 名患者，并分为三组：TDF 浓度 <40（11.7%）、40-90（36.8%）和 >90（高水平组，51.5%）ng/mL。在 TDF 起始时和 Ctrough-TDF 测定时以及 12 个月后，使用 Cockcroft-Gault、改良肾脏病饮食研究和慢性肾脏病流行病学合作公式测量 GFR。
在 Ctrough-TDF 测量时，基于 TDF 的治疗中位时间为 21.1 个月。高水平组 GFR 明显下降（-8.5 mL/min；P < 0.001），无论使用何种方法。GFR 下降与年龄较大显著相关。性别分层分析显示，仅在女性中，Ctrough-TDF >90 ng/mL 的早期影响显著。12 个月后，男性和女性高 Ctrough-TDF 患者的 GFR 下降（-8.27；P = 0.003）。
高浓度的 Ctrough-TDF 及其与肾功能损害风险增加的相关性支持 TDF 治疗药物监测的有用性，特别是在女性和老年患者中。
