依非韦伦、替诺福韦和恩曲他滨在肥胖中的浓度：一项横断面研究。
Concentrations of Efavirenz, Tenofovir, and Emtricitabine in Obesity: A Cross-Sectional Study.
机构信息
Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Division of Medical Physiology, Department of Biomedical Sciences, Centre for Cardio-metabolic Research in Africa (CARMA), Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
出版信息
J Acquir Immune Defic Syndr. 2022 Sep 1;91(1):101-108. doi: 10.1097/QAI.0000000000003025.
BACKGROUND
Obesity is increasing worldwide including in people living with HIV (PLWH). Antiretroviral pharmacokinetic data in obesity are limited.
OBJECTIVES
To measure antiretroviral drug concentrations in obese and nonobese PLWH treated with the fixed-dose combination of efavirenz-tenofovir-emtricitabine. To determine pharmacokinetic differences across indicators of obesity and their associated immunovirological outcomes.
METHODS
We conducted a cross-sectional sample analysis of 2 cohort studies. We measured mid-dose efavirenz, 8-hydroxy-efavirenz, tenofovir, and emtricitabine concentrations. Antiretroviral drug concentrations were analyzed by body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR).
RESULTS
We performed a study of 213 participants: General obesity was detected in 20.4% using BMI and abdominal obesity in 53.6% using WC and 62.4% using WHR, respectively. The median concentrations of all antiretroviral drugs were lower among obese participants determined by BMI and WC, with efavirenz showing greater differences than tenofovir or emtricitabine. For BMI, results were most striking for efavirenz (1752.3 vs 2342.9 ng/mL, P = 0.002) with lower concentrations in obese participants. Using WC, efavirenz (1845.8 vs 2571.2 ng/mL, P < 0.001), tenofovir (65.8 vs 73.2 ng/mL, P = 0.036), and emtricitabine (159.5 vs 221.0 ng/mL, P = 0.005) concentrations were lower in obese participants. Eight-hydroxyefavirenz concentrations were similar in nonobese and obese participants for WC. Using WHR, the concentrations of all antiretroviral drugs were lower in the obese population, most strikingly for emtricitabine (173.5 vs 229.0 ng/mL, P = 0.015). There were no immunovirological associations.
CONCLUSION
We found lower antiretroviral concentrations in all obese groups, most strikingly in participants with abdominal obesity determined by WC. Lower drug concentrations had no immunovirological associations.
背景
肥胖症在全球范围内不断增加，包括艾滋病毒感染者（PLWH）。肥胖症患者的抗逆转录病毒药代动力学数据有限。
目的
测量固定剂量组合依非韦伦-替诺福韦-恩曲他滨治疗肥胖和非肥胖 PLWH 的抗逆转录病毒药物浓度。确定肥胖指标的药代动力学差异及其相关免疫病毒学结果。
方法
我们对 2 项队列研究进行了横断面样本分析。我们测量了中剂量依非韦伦、8-羟基依非韦伦、替诺福韦和恩曲他滨的浓度。抗逆转录病毒药物浓度通过体重指数（BMI）、腰围（WC）和腰臀比（WHR）进行分析。
结果
我们对 213 名参与者进行了一项研究：BMI 检测到 20.4%的普通肥胖，WC 检测到 53.6%的腹部肥胖，WHR 检测到 62.4%的腹部肥胖。根据 BMI 和 WC，所有抗逆转录病毒药物的中位数浓度在肥胖参与者中较低，依非韦伦的差异大于替诺福韦或恩曲他滨。对于 BMI，结果最显著的是依非韦伦（1752.3 与 2342.9 ng/mL，P=0.002），肥胖参与者的浓度较低。使用 WC，依非韦伦（1845.8 与 2571.2 ng/mL，P<0.001）、替诺福韦（65.8 与 73.2 ng/mL，P=0.036）和恩曲他滨（159.5 与 221.0 ng/mL，P=0.005）的浓度在肥胖参与者中较低。WC 中 8-羟基依非韦伦浓度在非肥胖和肥胖参与者中相似。使用 WHR，所有抗逆转录病毒药物在肥胖人群中的浓度较低，恩曲他滨的浓度最为显著（173.5 与 229.0 ng/mL，P=0.015）。没有免疫病毒学关联。
结论
我们发现所有肥胖组的抗逆转录病毒药物浓度较低，以 WC 确定的腹部肥胖参与者最为显著。较低的药物浓度与免疫病毒学无关。
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