Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
Johns Hopkins University School of Medicine, Baltimore, Maryland.
Clin Infect Dis. 2018 Aug 16;67(5):778-784. doi: 10.1093/cid/ciy151.
Age-related gait speed decline is accelerated in men with human immunodeficiency virus (HIV). Mitochondrial genetic variation is associated with frailty and mortality in the general population and may provide insight into mechanisms of functional decline in people aging with HIV.
Gait speed was assessed semiannually in the Multicenter AIDS Cohort Study. Mitochondrial DNA (mtDNA) haplogroups were extracted from genome-wide genotyping data, classifying men aged ≥50 years into 5 groups: mtDNA haplogroup H, J, T, Uk, and other. Differences in gait speed by haplogroups were assessed as rate of gait speed decline per year, probability of slow gait speed (<1.0 m/s), and hazard of slow gait using multivariable linear mixed-effects models, mixed-effects logistic regression models, and the Andersen-Gill model, controlling for hepatitis C virus infection, previous AIDS diagnosis, thymidine analogues exposure, education, body composition, smoking, and peripheral neuropathy. Age was further controlled for in the mixed-effects logistic regression models.
A total of 455 HIV-positive white men aged ≥50 years contributed 3283 person-years of follow-up. Among them, 70% had achieved HIV viral suppression. In fully adjusted models, individuals with haplogroup J had more rapid decline in gait speed (adjusted slopes, 0.018 m/s/year vs 0.011 m/s/year, pinteraction = 0.012) and increased risk of developing slow gait (adjusted odds ratio, 2.97; 95% confidence interval, 1.24-7.08) compared to those with other haplogroups.
Among older, HIV-infected men, mtDNA haplogroup J was an independent risk factor for more rapid age-related gait speed decline.
与普通人群相比，感染人类免疫缺陷病毒（HIV）的男性其与年龄相关的步态速度下降更为迅速。线粒体遗传变异与虚弱和死亡率有关，可能为了解 HIV 感染者衰老过程中功能下降的机制提供线索。
在多中心艾滋病队列研究中，每半年评估一次步态速度。从全基因组基因分型数据中提取线粒体 DNA（mtDNA）单倍群，将年龄≥50 岁的男性分为 5 组：mtDNA 单倍群 H、J、T、Uk 和其他。使用多变量线性混合效应模型、混合效应逻辑回归模型和 Andersen-Gill 模型评估单倍群之间的步态速度差异，以每年步态速度下降率、慢步态速度（<1.0m/s）的概率和慢步态的危险比来表示，控制丙型肝炎病毒感染、既往 AIDS 诊断、胸苷类似物暴露、教育程度、身体成分、吸烟和周围神经病变。在混合效应逻辑回归模型中，进一步控制了年龄。
共有 455 名年龄≥50 岁的 HIV 阳性白人男性，随访时间共 3283 人年。其中，70%的人实现了 HIV 病毒抑制。在完全调整的模型中，具有单倍群 J 的个体步态速度下降更快（调整斜率，0.018m/s/年比 0.011m/s/年，p 交互=0.012），且发展为慢步态的风险增加（调整比值比，2.97；95%置信区间，1.24-7.08）。
在年龄较大的 HIV 感染者中，mtDNA 单倍群 J 是与年龄相关的步态速度快速下降的独立危险因素。
