Epigenetic age acceleration changes 2 years after antiretroviral therapy initiation in adults with HIV: a substudy of the NEAT001/ANRS143 randomised trial
Epigenetic age acceleration changes 2 years after antiretroviral therapy initiation in adults with HIV: a substudy of the NEAT001/ANRS143 randomised trial
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DOI：
10.1016/s2352-3018(21)00006-0
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发表时间：
2021-04-01
期刊：
影响因子：
16.1
通讯作者：
Arribas, Jose R.
中科院分区：
文献类型：
--
作者：
Esteban-Cantos, Andres;Rodriguez-Centeno, Javier;Arribas, Jose R.
基于DNA甲基化的生物学年龄估计是衰老过程的可靠生物标志物。我们的目的是调查一系列表观遗传衰老生物标志物在一个subshrdy的NEAT 001/ANRS 143临床试验，比较利托那韦加强darunavir与任一雷特格韦或替诺福韦二异山梨醇富马酸酯和恩曲他滨在抗逆转录病毒治疗（ART）初治adults.Methods我们分析了冷冻全血样本从168 ART初治参与者与HIV从NEAT 001/ANRS 143试验，ART开始前和ART 2年后（84名受试者接受利托那韦加强的地瑞那韦与雷特格韦，84名受试者接受利托那韦加强的地瑞那韦与富马酸替诺福韦二异丙酯和恩曲他滨）。我们还纳入了44名没有艾滋病毒的参与者，他们的年龄和性别分布相似。我们分析了DNA甲基化。使用Horvath的新在线甲基化年龄计算器和Houseman的方法生成表观遗传年龄估计值（Horvath的时钟，Hannum的时钟，GrimAge和PhenoAge）和估计的白细胞组成。我们计算了表观遗传年龄加速措施的表观遗传年龄的每个估计。NEAT 001/ANRS 143试验在www.example.com注册ClinicalTrials.gov，NCT 01066962。结果与HIV未感染组相比，根据所有EAA估计值，未接受ART的HIV受试者表现出更高的表观遗传年龄加速（EAA）（Horvath-EAA组平均2.5年，95%CI 1.89-3-22; Hannum-EAA组平均1.4年，0.74-1.99; Grimantine-EAA组平均2.8年，1.97-3-68;和7.3年，6.40-8.13对于Phenoestrogen-EAA），除了Hannum-EAA（Horvath-EAA p=0.0008; Hannum-EAA p=0.059; Grimestrogen-EAA p =0.0021;和Phenoestrogen-EAA p= 0.0001），所有差异都具有统计学显著性。
Background DNA methylation-based estimators of biological age are reliable biomarkers of the ageing process. We aimed to investigate a range of epigenetic ageing biomarkers in a subshrdy of the NEAT001/ANRS143 clinical trial, which compared ritonavir-boosted darunavir with either raltegravir or tenofovir disoproxil fumarate and emtricitabine in antiretroviral therapy (ART)-naive adults.Methods We analysed frozen whole blood samples from 168 ART-naive participants with HIV from the NEAT001/ANRS143 trial, before ART initiation and after 2 years of ART (84 participants on ritonavir-boosted darunavir with raltegravir and 84 participants on ritonavir-boosted darunavir with tenofovir disoproxil fumarate and emtricitabine). We also included 44 participants without HIV with a similar age and sex distribution. We analysed DNA methylation. Epigenetic age estimators (Horvath's clock, Hannum's clock, GrimAge, and PhenoAge) and estimated leucocyte compositions were generated using Horvath's New Online Methylation Age Calculator and Houseman's method. We calculated epigenetic age acceleration measures for each estimator of epigenetic age. The NEAT001/ANRS143 trial is registered with ClinicalTrials.gov, NCT01066962.Findings Compared with the HIV-uninfected group, ART-naive participants with HIV showed higher epigenetic age acceleration (EAA) according to all EAA estimators (mean 2.5 years, 95% CI 1.89-3-22 for Horvath-EAA; 1.4 years, 0.74-1.99 for Hannum-EAA; 2.8 years, 1.97-3-68 for GrimAge-EAA; and 7.3 years, 6.40-8.13 for PhenoAge-EAA), with all differences being statistically significant except for Hannum-EAA (Horvath-EAA p=0.0008; Hannum-EAA p=0.059; GrimAge-EAA p=0.0021; and PhenoAge-EAA p