Lower Pretreatment Gut Integrity Is Independently Associated With Fat Gain on Antiretroviral Therapy
Lower Pretreatment Gut Integrity Is Independently Associated With Fat Gain on Antiretroviral Therapy
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DOI：
10.1093/cid/ciy716
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发表时间：
2019-04-15
影响因子：
11.8
通讯作者：
McComsey, Grace A.
中科院分区：
文献类型：
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作者：
El Kamari, Vanessa;Moser, Carlee;McComsey, Grace A.
背景资料。脂肪堆积和胰岛素抵抗仍然是抗逆转录病毒治疗(ART)成功的威胁。肠道功能障碍在抗逆转录病毒治疗相关代谢并发症中的作用尚不清楚。人类免疫缺陷病毒(HIV)感染的ART幼稚参与者被随机分为富马酸替诺福韦/恩曲他滨联合阿扎那韦/利托那韦、达鲁那韦/利托那韦或雷替格列韦(Ral)。观察96周后肠道完整性标志物带状蛋白、脂多糖结合蛋白(LBP)、肠脂肪酸和回肠胆汁酸结合蛋白(I-FABP和I-BABP)的变化。用Wilcoxon秩和检验比较组间变化和线性回归模型，以量化肠道标志物、胰岛素抵抗、体重指数(BMI)和内脏、皮下和总脂肪组织(VAT、SAT和TAT)之间的关系。包括231名参与者：90%是男性，48%是非西班牙裔白人。中位年龄为36岁，HIV-1核糖核酸为4.56log10拷贝/毫升，CD4计数为338个/亩L。在96周内，I-FABP总体上增加了1.7倍，两组之间没有差异。与以蛋白酶抑制剂为基础的治疗方案相比，服用Ral后，Zonrin水平升高(第96周，P=0.02)；I-BABP或LBP水平变化很小。较高的基线I-FABP水平与增值税、TAT和BMI的增加相关(分别为16%、9%和2.5%；P
Background. Fat accumulation and insulin resistance remain a threat to the success of antiretroviral therapy (ART). The role of gut dysfunction in metabolic complications associated with ART initiation is unclear.Methods. Human immunodeficiency virus (HIV)-infected ART-naive participants were randomized to tenofovir disoproxil fumarate/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir (RAL). Changes in the gut integrity markers zonulin, lipopolysaccharide-binding protein (LBP), and intestinal fatty acid and ileal bile acid binding proteins (I-FABP and I-BABP) were assessed over 96 weeks. Wilcoxon rank-sum tests were used to compare changes between groups and linear regression models to quantify associations between gut markers, insulin resistance, body mass index (BMI), and visceral, subcutaneous, and total adipose tissue (VAT, SAT, and TAT).Results. There were 231 participants included: 90% were male and 48% were White non-Hispanic. The median age was 36 years, HIV-1 ribonucleic acid was 4.56 log 10 copies/mL, and CD4 count was 338 cells/mu L. An overall 1.7-fold increase in I-FABP was observed throughout 96 weeks, with no difference between arms. Zonulin levels increased with RAL compared to protease inhibitor- based regimens (week 96, P=.02); minimal changes in I-BABP or LBP levels were observed. Higher baseline I-FABP levels were associated with increases in VAT, TAT, and BMI (16%, 9%, and 2.5%, respectively; P