Background 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. Methods 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. Results 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. Conclusions Among older, HIV-infected men, mtDNA haplogroup J was an independent risk factor for more rapid age-related gait speed decline.

中文翻译：

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线粒体 DNA 变异在患有人类免疫缺陷病毒的老年男性中与年龄相关的步速下降中的作用。

背景 在患有人类免疫缺陷病毒 (HIV) 的男性中，与年龄相关的步态速度下降会加速。线粒体遗传变异与普通人群的虚弱和死亡率相关，并可能提供对艾滋病毒感染者功能衰退机制的深入了解。方法 在多中心 AIDS 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，将单倍群的步态速度差异评估为每年的步态速度下降率、慢步态速度 (<1.0 m/s) 的概率和慢步态的危险，和安徒生吉尔模型，控制丙型肝炎病毒感染、先前的艾滋病诊断、胸苷类似物暴露、教育、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。结果共有 455 名年龄≥50 岁的 HIV 阳性白人男性进行了 3283 人年的随访。其中，70%实现了HIV病毒抑制。在完全调整的模型中，具有单倍群 J 的个体的步态速度下降更快（调整后的斜率，0.018 m/s/年 vs 0.011 m/s/年，pinteraction = 0.012）并且发展缓慢步态的风险增加（调整优势比， 2.97；95% 置信区间，1.24-7.08）与其他单倍群相比。结论 在感染 HIV 的老年男性中，mtDNA 单倍群 J 是与年龄相关的步态速度更快下降的独立危险因素。