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抗逆转录病毒联合疗法与人类免疫缺陷病毒感染者端粒长度之间的关联

Association between Combination Antiretroviral Therapy and Telomere Length in People Living with Human Immunodeficiency Virus.

作者信息

Bukic Ena, Milasin Jelena, Toljic Bosko, Jadzic Jelena, Jevtovic Djordje, Obradovic Bozana, Dragovic Gordana

机构信息

Department of Pharmacology, Clinical Pharmacology and Toxicology, University of Belgrade Faculty of Medicine, 11000 Belgrade, Serbia.

Department of Human Genetics, School of Dental Medicine, University of Belgrade, 11000 Belgrade, Serbia.

出版信息

Biology (Basel). 2023 Sep 5;12(9):1210. doi: 10.3390/biology12091210.

Abstract

Long-term exposure to combination antiretroviral therapy (cART) may be associated with accelerated ageing. Telomere length is considered to be reliable aging biomarker. The aim of this study was to compare patients' relative telomere length (RTL) between and within different cART classes and to estimate the impact of certain HIV-related variables on RTL. The study was conducted in 176 HIV-infected male patients receiving cART, with ≤50 copies HIV RNA/mL plasma. RTL was determined from mononuclear cells by quantitative polymerase chain reaction. Standard statistical tests and unsupervised machine learning were performed. The mean RTL was 2.50 ± 1.87. There was no difference ( = 0.761) in RTL between therapeutic groups: two nucleoside reverse transcriptase inhibitors as the backbone treatment, combined with either integrase inhibitor, protease inhibitor, or non-nucleoside reverse transcriptase inhibitor (NNRTI). Machine learning results suggested duration of HIV infection, CD4+ T-cell count, and cART, including NNRTI, as potentially significant variables impacting RTL. Kendall's correlation test excluded duration of HIV infection ( = 0.220) and CD4+ T-cell count ( = 0.536) as significant. The Mann-Whitney test confirmed that cART containing NNRTI impacted RTL ( = 0.018). This was the first study to show that patients using efavirenz within cART had significantly shorter telomeres than patients using nevirapine.

摘要

长期接受联合抗逆转录病毒疗法(cART)可能与加速衰老有关。端粒长度被认为是可靠的衰老生物标志物。本研究的目的是比较不同cART类别之间以及类别内部患者的相对端粒长度(RTL),并评估某些与HIV相关的变量对RTL的影响。该研究在176名接受cART治疗且血浆HIV RNA≤50拷贝/mL的HIV感染男性患者中进行。通过定量聚合酶链反应从单核细胞中测定RTL。进行了标准统计测试和无监督机器学习。平均RTL为2.50±1.87。治疗组之间的RTL无差异(P = 0.761):以两种核苷类逆转录酶抑制剂为骨干治疗,联合整合酶抑制剂、蛋白酶抑制剂或非核苷类逆转录酶抑制剂(NNRTI)。机器学习结果表明,HIV感染持续时间、CD4 + T细胞计数以及包括NNRTI在内的cART是影响RTL的潜在重要变量。肯德尔相关性检验排除了HIV感染持续时间(P = 0.220)和CD4 + T细胞计数(P = 0.536)具有显著性。曼 - 惠特尼检验证实,含NNRTI的cART会影响RTL(P = 0.018)。这是第一项表明在cART中使用依非韦伦的患者端粒明显短于使用奈韦拉平的患者的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df76/10525818/14eac9391b99/biology-12-01210-g001.jpg

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