Madelain Vincent, Le Minh P, Champenois Karen, Charpentier Charlotte, Landman Roland, Joly Veronique, Yeni Patrick, Descamps Diane, Yazdanpanah Yazdan, Peytavin Gilles
IAME, UMR 1137, Université Paris Diderot, Sorbonne Paris Cité and INSERM, Paris F-75018, France.
AP-HP, Hôpital Bichat-Claude Bernard, Laboratoire de Pharmaco-Toxicologie, Paris F-75018, France.
J Antimicrob Chemother. 2017 Apr 1;72(4):1137-1146. doi: 10.1093/jac/dkw527.
Obesity has high prevalence among HIV-infected patients. Increased adipose tissue mass affects the pharmacokinetics of numerous drugs, but few data are available for antiretroviral drugs.
In this study we aimed to explore the pharmacokinetics of antiretroviral drugs and the immuno-virological response in obese patients with HIV infection.
We examined data from 2009 to 2012 in our hospital's database for HIV-1-infected patients who received an antiretroviral drug (abacavir, emtricitabine, lamivudine, tenofovir, efavirenz, etravirine, nevirapine, atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir or raltegravir). Obese patients were defined as those with BMI ≥30 kg/m 2 and normal-weight patients as those with BMI 19-25 kg/m 2 . Plasma concentrations ( C 12/24 ) were compared for each antiretroviral drug using a Mann-Whitney test. Suboptimal dosing and virological outcome were assessed by logistic regression, adjusting on covariates.
We enrolled 291 obese and 196 normal-weight patients. Among the 12 analysed antiretroviral drugs, tenofovir, efavirenz and lopinavir C 12 values were significantly lower in obese than normal-weight patients: 66 versus 86 ng/mL, 1498 versus 2034 ng/mL and 4595 versus 6420 ng/mL, respectively ( P < 0.001). Antiretroviral drug C 12/24 values were more frequently below efficacy thresholds for obese than for normal-weight patients after adjustment for other covariates ( P < 0.001). Although obese patients showed a higher CD4 count than normal-weight patients (510 versus 444 cells/mm 3 , P < 0.001), the groups did not differ in virological failure rate.
This study highlights the impact of obesity on antiretroviral drug plasma exposure, but identifies no consequence of this suboptimal exposure on the immuno-virological control in this population.
肥胖在感染HIV的患者中普遍存在。脂肪组织量增加会影响多种药物的药代动力学，但抗逆转录病毒药物的数据较少。
在本研究中，我们旨在探讨肥胖的HIV感染患者中抗逆转录病毒药物的药代动力学及免疫病毒学反应。
我们研究了我院数据库中2009年至2012年期间接受抗逆转录病毒药物（阿巴卡韦、恩曲他滨、拉米夫定、替诺福韦、依非韦伦、依曲韦林、奈韦拉平、阿扎那韦/利托那韦、达芦那韦/利托那韦、洛匹那韦/利托那韦或拉替拉韦）治疗的HIV-1感染患者的数据。肥胖患者定义为BMI≥30 kg/m²，体重正常患者定义为BMI 19 - 25 kg/m²。使用Mann-Whitney检验比较每种抗逆转录病毒药物的血浆浓度（C12/24）。通过逻辑回归评估次优剂量和病毒学结果，并对协变量进行校正。
我们纳入了291例肥胖患者和196例体重正常患者。在分析的12种抗逆转录病毒药物中，肥胖患者的替诺福韦、依非韦伦和洛匹那韦C12值显著低于体重正常患者：分别为66 ng/mL对86 ng/mL、1498 ng/mL对2034 ng/mL、4595 ng/mL对6420 ng/mL（P < 0.001）。在对其他协变量进行校正后，肥胖患者的抗逆转录病毒药物C12/24值低于疗效阈值的情况比体重正常患者更常见（P < 0.001）。尽管肥胖患者的CD4细胞计数高于体重正常患者（510个/mm³对444个/mm³，P < 0.001），但两组的病毒学失败率没有差异。
本研究强调了肥胖对抗逆转录病毒药物血浆暴露的影响，但未发现这种次优暴露对该人群免疫病毒学控制有任何影响。
