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短白细胞端粒长度与 HIV 感染的队列研究相关性:无证据表明与抗逆转录病毒治疗有关。

Association between short leukocyte telomere length and HIV infection in a cohort study: No evidence of a relationship with antiretroviral therapy.

机构信息

Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver.

出版信息

Clin Infect Dis. 2014 May;58(9):1322-32. doi: 10.1093/cid/ciu051. Epub 2014 Jan 22.

Abstract

BACKGROUND

Individuals infected with human immunodeficiency virus (HIV) appear to age faster than the general population, possibly related to HIV infection, antiretroviral therapy, and/or social/environmental factors. We evaluated leukocyte telomere length (LTL), a marker of cellular aging, in HIV-infected and uninfected adults.

METHODS

Clinical data and blood were collected from Children and women: AntiRetrovirals and the Mechanism of Aging (CARMA) cohort study participants. Variables found to be important in univariate analysis were multivariate model candidates.

RESULTS

Of the 229 HIV-infected and 166 HIV-uninfected participants, 76% were women, and 71% were current/previous smokers. In a multivariate model of all participants, older age (P < .001), HIV infection (P = .04), active hepatitis C virus (HCV) infection (P = .02), and smoking (P < .003) were associated with shorter LTL. An interaction was detected, whereby smoking was associated with shorter LTL in HIV-uninfected subjects only. Among those, age and smoking (P ≤ .01) were related to shorter LTL. In 2 models of HIV-infected individuals, age (P ≤ .002) and either active HCV infection (P = .05) or peak HIV RNA ≥100 000 copies/mL (P = .04) were associated with shorter LTL, whereas other HIV disease or treatment parameters were unrelated.

CONCLUSIONS

Our results suggest that acquisition of HIV and viral load are primarily responsible for the association between HIV-positive status and shorter LTL. The lack of association between LTL and time since HIV diagnosis, antiretroviral treatment, or degree of immune suppression would implicate HIV infection-related factors rather than disease progression or treatment. Smoking effects on LTL appear masked by HIV, and HCV infection may accelerate LTL shortening, particularly in coinfected individuals. The effect of early therapeutic intervention on LTL in HIV and HCV infections should be evaluated.

摘要

背景

感染人类免疫缺陷病毒 (HIV) 的个体似乎比普通人群衰老得更快,这可能与 HIV 感染、抗逆转录病毒治疗和/或社会/环境因素有关。我们评估了 HIV 感染和未感染成年人的白细胞端粒长度 (LTL),这是细胞衰老的标志物。

方法

从儿童和妇女的抗逆转录病毒和衰老机制 (CARMA) 队列研究参与者中收集临床数据和血液。在单变量分析中发现重要的变量是多变量模型的候选变量。

结果

在 229 名 HIV 感染和 166 名 HIV 未感染的参与者中,76%为女性,71%为现/既往吸烟者。在所有参与者的多变量模型中,年龄较大(P<.001)、HIV 感染(P=0.04)、丙型肝炎病毒(HCV)感染活跃(P=0.02)和吸烟(P<.003)与较短的 LTL 相关。检测到交互作用,即吸烟与 HIV 未感染受试者的较短 LTL 相关。在这些人中,年龄和吸烟(P≤0.01)与较短的 LTL 相关。在 2 个 HIV 感染个体模型中,年龄(P≤0.002)和活跃的 HCV 感染(P=0.05)或峰值 HIV RNA≥100000 拷贝/ml(P=0.04)与较短的 LTL 相关,而其他 HIV 疾病或治疗参数与较短的 LTL 无关。

结论

我们的结果表明,获得 HIV 和病毒载量是 HIV 阳性状态与较短 LTL 之间关联的主要原因。LTL 与 HIV 诊断后时间、抗逆转录病毒治疗或免疫抑制程度之间缺乏关联,这表明与 HIV 感染相关的因素而不是疾病进展或治疗。吸烟对 LTL 的影响似乎被 HIV 掩盖,HCV 感染可能会加速 LTL 缩短,尤其是在合并感染的个体中。应评估早期治疗干预对 HIV 和 HCV 感染中 LTL 的影响。

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