Sinxadi Phumla Zuleika, McIlleron Helen Margaret, Dave Joel Alex, Smith Peter John, Levitt Naomi Sharlene, Haas David William, Maartens Gary
From the Division of Clinical Pharmacology, Department of Medicine, University of Cape Town (PZS, HMM, PJS, GM); Division of Endocrinology and Diabetic Medicine, Department of Medicine, University of Cape Town. Cape Town, South Africa (JAD, NSL); Vanderbilt University School of Medicine, Departments of Medicine, Pharmacology, Pathology, Microbiology & Immunology (DWH); Meharry Medical College, Department of Internal Medicine, Nashville, TN, United States of America (DWH).
Medicine (Baltimore). 2016 Jan;95(2):e2385. doi: 10.1097/MD.0000000000002385.
Efavirenz-based antiretroviral therapy (ART) has been associated with dyslipidemia and dysglycemia, risk factors for cardiovascular disease. However, the pathogenesis is not well understood. We characterized relationships between plasma efavirenz concentrations and lipid and glucose concentrations in HIV-infected South Africans.Participants on efavirenz-based ART were enrolled into a cross-sectional study. The oral glucose tolerance test was performed after an overnight fast, and plasma drawn for mid-dosing interval efavirenz, fasting total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and triglycerides concentrations.Among 106 participants (77 women), median age was 38 years, median CD4 + T-cell count was 322 cells/μL, median duration on ART was 18 months, and median (interquartile range) efavirenz concentration was 2.23 (1.66 to 4.10) μg/mL. On multivariable analyses (adjusting for age, sex, body mass index, and ART duration) doubling of efavirenz concentrations resulted in mean changes in mmol/L (95%CI) of: total cholesterol (0.40 [0.22 to 0.59]), LDL cholesterol (0.19 [0.04 to 0.30]), HDL cholesterol (0.14 [0.07 to 0.20]), triglycerides (0.17 [0.03 to 0.33]), fasting glucose (0.18 [0.03 to 0.33]), and 2-h glucose concentrations (0.33 [0.08 to 0.60]). Among 57 participants with CYP2B6 genotype data, associations between slow metabolizer genotypes and metabolic profiles were generally consistent with those for measured efavirenz concentrations.Higher plasma efavirenz concentrations are associated with higher plasma lipid and glucose concentrations. This may have implications for long-term cardiovascular complications of efavirenz-based ART, particularly among populations with high prevalence of CYP2B6 slow metabolizer genotypes.
基于依非韦伦的抗逆转录病毒疗法（ART）与血脂异常和血糖异常有关，而这两者都是心血管疾病的危险因素。然而，其发病机制尚未完全明确。我们对感染HIV的南非人血浆中依非韦伦浓度与血脂及血糖浓度之间的关系进行了特征描述。
接受基于依非韦伦的ART治疗的参与者被纳入一项横断面研究。在禁食过夜后进行口服葡萄糖耐量试验，并采集血浆以测定给药间隔中期的依非韦伦、空腹总胆固醇、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）胆固醇以及甘油三酯浓度。
在106名参与者（77名女性）中，中位年龄为38岁，中位CD4 + T细胞计数为322个/μL，ART治疗的中位时长为18个月，依非韦伦浓度的中位数（四分位间距）为2.23（1.66至4.10）μg/mL。在多变量分析（校正年龄、性别、体重指数和ART治疗时长）中，依非韦伦浓度翻倍导致总胆固醇（0.40 [0.22至0.59]）、LDL胆固醇（0.19 [0.04至0.30]）、HDL胆固醇（0.14 [0.07至0.20]）、甘油三酯（0.17 [0.03至0.33]）、空腹血糖（0.18 [0.03至0.33]）以及2小时血糖浓度（0.33 [0.08至0.60]）的平均变化（95%CI）。在57名有CYP2B6基因型数据的参与者中，慢代谢基因型与代谢谱之间的关联通常与所测依非韦伦浓度的关联一致。
较高的血浆依非韦伦浓度与较高的血浆脂质和葡萄糖浓度相关。这可能对基于依非韦伦的ART的长期心血管并发症有影响，尤其是在CYP2B6慢代谢基因型高流行率的人群中。
