Internal Medicine, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan.
PLoS One. 2019 Jun 27;14(6):e0218996. doi: 10.1371/journal.pone.0218996. eCollection 2019.
Telomere length (TL) is a marker of cellular and biological aging. Human immunodeficiency virus (HIV) infection has been reported to be associated with short TLs, which suggests that accelerated biological aging occurs in some cellular compartments of HIV+ individuals. In this study, we measured the TLs of peripheral leukocytes of HIV+ and healthy individuals and examined the biological and environmental correlates of TL. We also investigated the influence of TL on leukoaraiosis, an indicator of cerebral small vessel disease, in HIV+ individuals. Three hundred and twenty-five HIV+ individuals who received stable combination antiretroviral therapy (cART) for >1 year and achieved viral loads of <40 RNA copies/mL were enrolled along with 147 healthy individuals. Relative TLs of leukocytes were estimated by quantitative real-time polymerase chain reaction. Leukoaraiosis was assessed in 184 HIV+ individuals by fluid-attenuated inversion recovery magnetic resonance imaging. We analyzed several covariates, including markers of HIV infection, cART, and social/environmental factors; variables associated with TL length in univariate analyses were incorporated into multivariate models. The TLs of peripheral leukocytes of HIV+ individuals were significantly shorter than those of healthy individuals, and the rate of LT length decline with increasing age was greater. Linear regression analysis showed that in HIV+ individuals, increasing age, cART without integrase-stand transfer inhibitors (INSTI), failure to achieve viral loads of <40 copies/mL within 1 year of initiating cART, and substance use were significantly associated with shorter TLs, even after adjustment for the effects of age. Logistic regression analysis indicated an increasing risk of leukoaraiosis was associated with older age, shorter TLs, hypertension, and carotid artery plaque. Multivariate regression analysis indicated that older age and shorter TLs were significant risk factors for leukoaraiosis. In summary, our data showed that TL shortening in HIV+ individuals was independently associated with leukoaraiosis, and was associated with age, control of viral loads, use of INSTI, and substance use. Our results suggest that effective viral control and less toxic cART can help reduce TL shortening and improve outcomes among HIV+ individuals.
端粒长度（TL）是细胞和生物衰老的标志物。据报道，人类免疫缺陷病毒（HIV）感染与 TL 缩短有关，这表明 HIV+个体的某些细胞区室发生了加速的生物衰老。在这项研究中，我们测量了 HIV+和健康个体的外周白细胞的 TL，并检查了 TL 的生物学和环境相关性。我们还研究了 TL 对 HIV+个体中脑白质病变（leukoaraiosis）的影响，脑白质病变是脑小血管疾病的一个指标。我们招募了 325 名接受稳定联合抗逆转录病毒治疗（cART）超过 1 年且病毒载量<40 RNA 拷贝/ml 的 HIV+个体和 147 名健康个体。通过实时定量聚合酶链反应估计白细胞的相对 TL。通过液体衰减反转恢复磁共振成像（fluid-attenuated inversion recovery magnetic resonance imaging）评估了 184 名 HIV+个体的脑白质病变。我们分析了几种协变量，包括 HIV 感染标志物、cART 和社会/环境因素；在单变量分析中与 TL 长度相关的变量被纳入多变量模型。HIV+个体的外周白细胞 TL 明显短于健康个体，并且随着年龄的增长，TL 长度下降的速度更快。线性回归分析显示，在 HIV+个体中，年龄增长、未使用整合酶抑制剂（INSTI）的 cART、在开始 cART 后 1 年内未能实现病毒载量<40 拷贝/ml 以及物质使用与 TL 缩短显著相关，即使在调整年龄影响后也是如此。Logistic 回归分析表明，脑白质病变的风险随着年龄增长、TL 缩短、高血压和颈动脉斑块而增加。多变量回归分析表明，年龄增长和 TL 缩短是脑白质病变的显著危险因素。总之，我们的数据表明，HIV+个体的 TL 缩短与脑白质病变独立相关，与年龄、病毒载量控制、INSTI 使用和物质使用有关。我们的结果表明，有效的病毒控制和毒性较小的 cART 可以帮助减少 HIV+个体的 TL 缩短并改善其结局。
