Abdissa A, Olsen M F, Yilma D, Tesfaye M, Girma T, Christiansen M, Hagen C M, Wiesner L, Castel S, Aseffa A, McIlleron H, Pedersen C, Friis H, Andersen A B
Department of Medical Laboratory Sciences & Pathology, Jimma University, Jimma, Ethiopia.
Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
HIV Med. 2015 Aug;16(7):403-11. doi: 10.1111/hiv.12225. Epub 2015 May 13.
Lipid-based nutrient supplements (LNSs) are increasingly used in HIV programmes in resource-limited settings. However, the possible effects of LNSs on the plasma concentrations of antiretroviral drugs have not been assessed. Here, we aimed to assess the effects of LNSs on plasma efavirenz and nevirapine trough concentrations in Ethiopian adult HIV-infected patients.
The effects of LNSs were studied in adults initiating antiretroviral therapy (ART) in a randomized trial. Patients with body mass index (BMI) > 17 kg/m(2) (n = 282) received daily supplementation of an LNS containing whey (LNS/w), an LNS containing soy (LNS/s) or no LNS. Trough plasma concentrations of efavirenz and nevirapine were measured at 1 and 2 months. Genotyping for 516 G>T and 983 T>C polymorphisms of the cytochrome P450 (CYP) 2B6 locus was performed. Multilevel linear mixed-effects models were used to assess the associations between LNS and plasma efavirenz and nevirapine concentrations.
In patients with BMI > 17 kg/m(2), nevirapine concentrations were lower in the LNS/w and LNS/s groups by a median of -2.3 μg/mL [interquartile range (IQR) -3.9; -0.9 μg/mL; P = 0.002] and -2.1 μg/mL (IQR -3.9; -0.9 μg/mL; P = 0.01), respectively, compared with the group not receiving supplements. There were no differences between groups with respect to efavirenz plasma concentrations. The CYP2B6 516 G>T polymorphism was associated with a 5 μg/mL higher plasma efavirenz concentration compared with the wild type (P < 0.0001), while it was not associated with plasma nevirapine concentrations.
Intake of an LNS was associated with lower plasma nevirapine trough concentrations, indicating possible drug-LNS interactions. The clinical relevance of such reductions in nevirapine exposure is not clear. Plasma efavirenz concentration was not affected by the LNS.
在资源有限的环境中，基于脂质的营养补充剂（LNS）在艾滋病项目中的使用越来越多。然而，LNS对抗逆转录病毒药物血浆浓度的潜在影响尚未得到评估。在此，我们旨在评估LNS对埃塞俄比亚成年艾滋病病毒感染患者血浆中依非韦伦和奈韦拉平谷浓度的影响。
在一项随机试验中，对开始抗逆转录病毒治疗（ART）的成年人研究了LNS的影响。体重指数（BMI）>17kg/m²的患者（n = 282）每天补充含乳清的LNS（LNS/w）、含大豆的LNS（LNS/s）或不补充LNS。在第1个月和第2个月测量依非韦伦和奈韦拉平的血浆谷浓度。对细胞色素P450（CYP）2B6基因座的516G>T和983T>C多态性进行基因分型。使用多水平线性混合效应模型评估LNS与血浆依非韦伦和奈韦拉平浓度之间的关联。
在BMI>17kg/m²的患者中，与未接受补充剂的组相比，LNS/w组和LNS/s组的奈韦拉平浓度中位数分别降低了-2.3μg/mL[四分位间距（IQR）-3.9；-0.9μg/mL；P = 0.002]和-2.1μg/mL（IQR -3.9；-0.9μg/mL；P = 0.01）。各组之间依非韦伦血浆浓度没有差异。与野生型相比，CYP2B6 516G>T多态性与血浆依非韦伦浓度高5μg/mL相关（P<0.0001），而与血浆奈韦拉平浓度无关。
摄入LNS与较低的血浆奈韦拉平谷浓度相关，表明可能存在药物-LNS相互作用。奈韦拉平暴露量降低的临床相关性尚不清楚。血浆依非韦伦浓度不受LNS影响。
