Estrada V, Monge S, Gómez-Garre M D, Sobrino P, Masiá M, Berenguer J, Portilla J, Viladés C, Martínez E, Blanco J R
Hospital Clínico San Carlos-IdiSSC, Universidad Complutense, Madrid, Spain.
Universidad de Alcalá de Henares, CIBERESP, Spain.
HIV Med. 2016 Oct;17(9):653-61. doi: 10.1111/hiv.12368. Epub 2016 Mar 3.
Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV-infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UDP-glucuronosyl-transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line antiretroviral therapy (ART).
A multicentre, prospective cohort study of HIV-infected patients who started first-line ART with either ATV/r or EFV was conducted. Lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO) and oxidized low-density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders.
After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp-PLA2 [estimated difference -16.3; 95% confidence interval (CI) -31.4, -1.25; P = 0.03] and a significantly smaller increase in OxLDL (estimated difference -21.8; 95% CI -38.0, -5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI -14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated.
When compared with EFV, ATV/r-based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels.
慢性氧化应激（OS）可能在HIV感染患者的心血管疾病中起作用，而胆红素水平升高可能在对抗OS方面具有有益作用。阿扎那韦（ATV）抑制尿苷二磷酸葡萄糖醛酸基转移酶1A1（UGT1A1），从而增加未结合胆红素水平。我们旨在比较接受基于阿扎那韦/利托那韦（ATV/r）与依非韦伦（EFV）的一线抗逆转录病毒疗法（ART）的患者中OS标志物的变化。
对开始使用ATV/r或EFV进行一线ART的HIV感染患者进行了一项多中心前瞻性队列研究。在基线时以及至少9个月的ART后采集的样本中，对145例患者测量了脂蛋白相关磷脂酶A2（Lp-PLA2）、髓过氧化物酶（MPO）和氧化型低密度脂蛋白（oxLDL），在此期间维持初始治疗方案且患者病毒学抑制。使用多元线性回归对基线值和混杂因素进行调整，对OS标志物的变化进行建模。
在对基线变量进行调整后，与接受EFV治疗的患者相比，接受ATV/r治疗的患者Lp-PLA2的下降幅度显著更大[估计差异-16.3；95%置信区间（CI）-31.4，-1.25；P = 0.03]，oxLDL的升高幅度显著更小（估计差异-21.8；95% CI -38.0，-5.6；P < 0.01），而MPO的变化无显著差异（估计差异1.2；95% CI -14.3，16.7；P = 0.88）。ATV/r组胆红素的调整变化显著大于EFV组（估计差异1.33 mg/dL；95% CI 1.03，1.52 mg/dL；P < 0.01）。胆红素变化与OS标志物变化显著相关。
与EFV相比，基于ATV/r的治疗与较低水平的氧化应激生物标志物相关，这部分归因于胆红素水平升高。
