Institute of Health Carlos III, Madrid, Spain.
Hospital La Paz Institute for Health Research, Madrid, Spain.
HIV Med. 2019 Nov;20(10):691-698. doi: 10.1111/hiv.12791. Epub 2019 Sep 18.
Our aim was to investigate factors associated with baseline blood telomere length in participants enrolled in NEAT 001/ANRS 143, a randomized, open-label trial comparing ritonavir-boosted darunavir (DRV/r) plus raltegravir (RAL) with DRV/r plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in antiretroviral therapy (ART)-naïve HIV-positive adults.
A cross-sectional study of 201 randomly selected participants who had stored samples available was carried out. We measured telomere length (i.e. the relative telomere length, calculated as the telomere to single copy gene ratio) at baseline with monochrome quantitative multiplex polymerase chain reaction (PCR). We used multivariable predictive linear regression to calculate mean differences and 95% confidence intervals (CIs) for the association between baseline telomere length and baseline characteristics.
The baseline characteristics of the 201 participants did not differ from those of the 805 participants in the parent trial population: 89% were male, the mean age was 39 years, 83.6% were Caucasian, 93% acquired HIV infection via sexual transmission, the mean estimated time since HIV diagnosis was 2.1 years, the mean HIV-1 RNA load was 4.7 log HIV-1 RNA copies/mL, the mean nadir and baseline CD4 counts were 301 and 324 cells/μL, respectively, and the mean CD4:CD8 ratio was 0.4. In the univariate analysis, shorter telomere length was associated with older age (per 10 years) (P < 0.001), HIV-1 RNA ≥ 100 000 copies/mL (P = 0.001), CD4 count < 200 cells/μL (P = 0.037), lower CD4:CD8 ratio (P = 0.018), statin treatment (P = 0.004), and current alcohol consumption (P = 0.035). In the multivariable analysis, older age (P < 0.001) and HIV RNA ≥ 100 000 copies/mL (P = 0.054) were independently associated with shorter telomere length.
Both age and HIV RNA viral load correlated with shorter blood telomere length in untreated persons living with HIV. These results suggest that HIV infection and age have synergistic and independent impacts upon immunosenescence.
本研究旨在调查参加 NEAT 001/ANRS 143 研究的参与者中与基线血液端粒长度相关的因素，该研究为一项比较利托那韦增强的达芦那韦（DRV/r）联合拉替拉韦（RAL）与 DRV/r 联合替诺福韦二吡呋酯/恩曲他滨（TDF/FTC）在初治 HIV 阳性成人中的疗效的随机、开放标签试验。
对 201 名随机选择且有存储样本的参与者进行横断面研究。使用单色定量多重聚合酶链反应（PCR）测量基线时的端粒长度（即相对端粒长度，计算为端粒与单拷贝基因的比值）。我们使用多变量预测线性回归计算基线端粒长度与基线特征之间关联的平均差异和 95%置信区间（CI）。
201 名参与者的基线特征与主要试验人群中的 805 名参与者的特征无差异：89%为男性，平均年龄为 39 岁，83.6%为白种人，93%通过性传播感染 HIV，估计 HIV 诊断后时间平均为 2.1 年，平均 HIV-1 RNA 载量为 4.7 log HIV-1 RNA 拷贝/mL，最低和基线 CD4 计数分别为 301 和 324 个/μL，CD4:CD8 比值平均为 0.4。在单变量分析中，端粒较短与年龄较大（每 10 岁）（P<0.001）、HIV-1 RNA≥100000 拷贝/mL（P=0.001）、CD4 计数<200 个/μL（P=0.037）、较低的 CD4:CD8 比值（P=0.018）、他汀类药物治疗（P=0.004）和当前饮酒（P=0.035）相关。在多变量分析中，年龄较大（P<0.001）和 HIV RNA≥100000 拷贝/mL（P=0.054）与端粒较短独立相关。
在未经治疗的 HIV 感染者中，年龄和 HIV RNA 病毒载量均与较短的血液端粒长度相关。这些结果表明，HIV 感染和年龄对免疫衰老有协同和独立的影响。
