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中国HIV患者队列中高效抗逆转录病毒治疗后免疫恢复与高脂血症及载脂蛋白基因多态性的关联

Association of immune recovery with hyperlipidaemia and apolipoprotein gene polymorphisms following highly active antiretroviral therapy in a cohort of Chinese HIV patients.

作者信息

Chan Denise Pui-Chung, Lee Man-Po, Wong Ngai-Sze, Leung Ross Ka-Kit, Naftalin Claire Melinda, Lee Shui-Shan

机构信息

Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong, People's Republic of China.

Department of Medicine, Queen Elizabeth Hospital, Kowloon, Hong Kong, People's Republic of China.

出版信息

BMJ Open. 2016 Apr 11;6(4):e010998. doi: 10.1136/bmjopen-2015-010998.

Abstract

OBJECTIVE

To examine the associations between CD4 recovery, dyslipidaemia and apolipoprotein (APO) gene single nucleotide polymorphisms (SNPs) following highly active antiretroviral therapy (HAART).

DESIGN

Retrospective observational cohort study.

SETTING

A major HIV care clinic in Hong Kong.

PARTICIPANTS

197 Chinese treatment-naïve HIV patients.

OUTCOME MEASURES

Maximum CD4 count and its rise 2-3 years after HAART initiation and their association with abnormal total cholesterol (TC), triglyceride (TG) and 8 selected APO SNP at multiple time points.

RESULTS

Before HAART, abnormal levels of TC, TG, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were detected in 13%, 26%, 59% and 19% of the recruited patients, respectively. APOA5 -1131T>C and c.553G>T were significantly associated with high pre-HAART TG while APOE 2198C>T was correlated with high TG at baseline and/or a rise 2-3 years following HAART initiation. Poor CD4 achievement, defined as the highest CD4 count <350/μL and a net gain of <100/μL, was associated with a low CD4 count ≤200/μL at baseline and a rise of TC beyond 5.17 mmol/L following HAART with or without the use of antilipid agents. Conversely, satisfactory CD4 achievement was associated with APOC3 3238GG genotype. Applying a linear generalised estimating equation, APOA5 -1131T>C was shown to be a predictor of a weaker temporal trend for CD4 response in the presence of a low baseline CD4≤200/μL.

CONCLUSIONS

Dyslipidaemia plays a predictive role in impacting immunological recovery following HAART, which could be partly explained by the APO gene SNP.

摘要

目的

研究高效抗逆转录病毒治疗(HAART)后CD4细胞恢复、血脂异常与载脂蛋白(APO)基因单核苷酸多态性(SNP)之间的关联。

设计

回顾性观察队列研究。

地点

香港一家主要的HIV护理诊所。

参与者

197例未接受过治疗的中国HIV患者。

观察指标

HAART开始后2 - 3年的最高CD4细胞计数及其升高情况,以及它们与多个时间点的总胆固醇(TC)、甘油三酯(TG)异常和8个选定的APO SNP的关联。

结果

在HAART之前,分别有13%、26%、59%和19%的入组患者检测到TC、TG、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇水平异常。APOA5 -1131T>C和c.553G>T与HAART前高TG显著相关,而APOE 2198C>T与基线时高TG和/或HAART开始后2 - 3年的升高相关。CD4细胞恢复不佳定义为最高CD4细胞计数<350/μL且净增加<100/μL,与基线时CD4细胞计数≤200/μL以及HAART后无论是否使用抗血脂药物TC升高超过5.17 mmol/L相关。相反,CD4细胞恢复良好与APOC3 3238GG基因型相关。应用线性广义估计方程,在基线CD4≤200/μL较低的情况下,APOA5 -1131T>C被证明是CD4反应较弱时间趋势的预测因子。

结论

血脂异常在影响HAART后的免疫恢复中起预测作用,这可能部分由APO基因SNP解释。

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