Barber Tristan J, Moyle Graeme, Hill Andrew, Singh Gurmit Jagjit, Boffito Marta, Nelson Mark
St Stephen's Centre, Chelsea and Westminster Hospital, London, UK.
J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19827. doi: 10.7448/IAS.17.4.19827. eCollection 2014.
Use of some protease inhibitors (PI) is associated with unconjugated hyperbilirubinaemia (HBR), due to inhibition of UGT1A1. As observed in Gilbert's syndrome, HBR may have antioxidant and anti-inflammatory effects. Inflammation may be relevant to neurocognitive (NC) impairment, cardiovascular, renal and bone co-morbidities in HIV infection. This study aimed to analyse correlations between antiretroviral associated HBR and NC impairment as well as renal, bone and cardiovascular parameters.
This cross-sectional study included 101 HIV-1-infected individuals stable (>6 months) on antiretroviral regimens including tenofovir/emtricitabine or abacavir/lamivudine plus a ritonavir-boosted PI. Patients with >grade 2 HBR were compared to patients with normal bilirubin on NC data collected using CogState. An overall composite score was calculated for each subject. Two-tail P-values were calculated using the Mann-Whitney U test. We measured the following parameters in all participants: Bone - Calcaneal Stiffness Index (CSI), blood bone markers, calculated FRAX score; CV - vascular endothelial function markers (iCAM, vCAM), lipid fractions and sub fractions (Total, HDL and LDL cholesterol, triglycerides, ApoB), Carotid Intimal Thickness (CIT), Pulse Wave Velocity (PWV), glucose and insulin for calculation of HOMA-IR, IL-6, d-dimer, uric acid, and hsCRP; Renal - urea and electrolytes (U&E), urinary protein/creatinine ratio (uPCR), urinary retinal binding protein (RBP)/creatinine ratio.
Forty-three participants had normal bilirubin (NBR) levels and 35 had high bilirubin (HBR; >2.5 times upper limit); the remaining 23 patients had intermediate bilirubin levels or violated the protocol. The mean age of participants was 48 years; 93% were male and 84% Caucasian. Mostly no significant differences were seen in any of the markers when comparing the NBR and HBR groups. Two component tests of the CogState were seen to be different - visual learning and memory (OCL) and working memory (ONB) (Table 1).
The numbers seen here were not felt to be large enough to draw clear conclusions around clinical significance. In the context of overall cognitive screening, the individual test differences were also not felt to be clinically significant. Clearly there are some early signs here of differences that may be worth investigating further in a larger, prospective study.
由于对尿苷二磷酸葡萄糖醛酸转移酶1A1（UGT1A1）的抑制作用，某些蛋白酶抑制剂（PI）的使用与非结合性高胆红素血症（HBR）相关。正如在吉尔伯特综合征中所观察到的，HBR可能具有抗氧化和抗炎作用。炎症可能与HIV感染中的神经认知（NC）损害、心血管、肾脏和骨骼合并症相关。本研究旨在分析抗逆转录病毒相关HBR与NC损害以及肾脏、骨骼和心血管参数之间的相关性。
这项横断面研究纳入了101名接受抗逆转录病毒治疗方案（包括替诺福韦/恩曲他滨或阿巴卡韦/拉米夫定加一种利托那韦增强的PI）且病情稳定（>6个月）的HIV-1感染者。将HBR>2级的患者与使用CogState收集的NC数据中胆红素正常的患者进行比较。为每个受试者计算一个总体综合评分。使用曼-惠特尼U检验计算双侧P值。我们在所有参与者中测量了以下参数：骨骼——跟骨硬度指数（CSI）、血骨标志物、计算的FRAX评分；心血管——血管内皮功能标志物（细胞间黏附分子-1、血管细胞黏附分子-1）、脂质组分和亚组分（总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、甘油三酯、载脂蛋白B）、颈动脉内膜中层厚度（CIT）、脉搏波速度（PWV）、用于计算胰岛素抵抗指数（HOMA-IR）的血糖和胰岛素、白细胞介素-6、D-二聚体、尿酸和超敏C反应蛋白（hsCRP）；肾脏——尿素和电解质（U&E）、尿蛋白/肌酐比值（uPCR）、尿视黄醇结合蛋白（RBP）/肌酐比值。
43名参与者胆红素（NBR）水平正常，35名参与者胆红素水平高（HBR；>上限的2.5倍）；其余23名患者胆红素水平处于中等或违反了方案。参与者的平均年龄为48岁；93%为男性，84%为白种人。在比较NBR组和HBR组时，在任何标志物中大多未观察到显著差异。CogState的两项成分测试存在差异——视觉学习和记忆（OCL）以及工作记忆（ONB）（表1）。
此处观察到的数量被认为不足以围绕临床意义得出明确结论。在总体认知筛查的背景下，个体测试差异也未被认为具有临床意义。显然，这里有一些差异的早期迹象，可能值得在更大规模的前瞻性研究中进一步调查。
