The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Centre of Excellence in Tuberculosis, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
BMC Geriatr. 2022 Dec 31;22(1):1010. doi: 10.1186/s12877-022-03720-1.
BACKGROUND: Aging characteristics in people living with HIV (PLWH) are heterogeneous, and the identification of risk factors associated with aging-related comorbidities such as neurocognitive impairment (NCI) and frailty is important. We evaluated predictors of novel aging markers, phenotypic age (PhenoAge) and phenotypic age acceleration (PAA) and their association with comorbidities, frailty, and NCI. METHODS: In a cohort of PLWH and age- and sex-matched HIV-negative controls, we calculated PhenoAge using chronological age and 9 biomarkers from complete blood counts, inflammatory, metabolic-, liver- and kidney-related parameters. PAA was calculated as the difference between chronological age and PhenoAge. Multivariate logistic regression models were used to identify the factors associated with higher (>median) PAA. Area under the receiver operating characteristics curve (AUROC) was used to assess model discrimination for frailty. RESULTS: Among 333 PLWH and 102 HIV-negative controls (38% female), the median phenotypic age (49.4 vs. 48.5 years, p = 0.54) and PAA (- 6.7 vs. -7.5, p = 0.24) was slightly higher and PAA slightly less in PLWH although this did not reach statistical significance. In multivariate analysis, male sex (adjusted odds ratio = 1.68 [95%CI = 1.03-2.73]), current smoking (2.74 [1.30-5.79]), diabetes mellitus (2.97 [1.48-5.99]), hypertension (1.67 [1.02-2.72]), frailty (3.82 [1.33-10.93]), and higher IL-6 levels (1.09 [1.04-1.15]), but not HIV status and NCI, were independently associated with higher PAA. PhenoAge marker discriminated frailty better than chronological age alone (AUROC: 0.75 [0.66-0.85] vs. 0.65 [0.55-0.77], p = 0.04). In the analysis restricted to PLWH, PhenoAge alone predicted frailty better than chronological age alone (AUROC: 0.7412 vs. 0.6499, P = 0.09) and VACS index (AUROC: 0.7412 vs. 0.6811, P = 0.34) despite not statistically significant. CONCLUSIONS: While PLWH did not appear to have accelerated aging in our cohort, the phenotypic aging marker was significantly associated with systemic inflammation, frailty, and cardiovascular disease risk factors. This simple aging marker could be useful to identify high-risk PLWH within a similar chronological age group.
背景：感染艾滋病毒（HIV）的人的衰老特征存在异质性，识别与神经认知障碍（NCI）和虚弱等与衰老相关的合并症相关的风险因素很重要。我们评估了新型衰老标志物，表型年龄（PhenoAge）和表型年龄加速（PAA）及其与合并症、虚弱和 NCI 的关联的预测因素。 方法：在一组 HIV 阳性和年龄、性别匹配的 HIV 阴性对照者中，我们使用生理年龄和全血细胞、炎症、代谢、肝脏和肾脏相关参数的 9 个生物标志物计算 PhenoAge。PAA 计算为生理年龄与 PhenoAge 之间的差异。多变量逻辑回归模型用于确定与较高（中位数以上）PAA 相关的因素。接收器操作特征曲线下面积（AUROC）用于评估对虚弱的模型区分度。 结果：在 333 名 HIV 阳性和 102 名 HIV 阴性对照者（38%为女性）中，表型年龄（49.4 岁比 48.5 岁，p=0.54）和 PAA（-6.7 岁比-7.5 岁，p=0.24）略高，PAA 略低，尽管这并未达到统计学意义。多变量分析显示，男性（调整优势比=1.68[95%CI=1.03-2.73]）、当前吸烟（2.74[1.30-5.79]）、糖尿病（2.97[1.48-5.99]）、高血压（1.67[1.02-2.72]）、虚弱（3.82[1.33-10.93]）和较高的 IL-6 水平（1.09[1.04-1.15]），而不是 HIV 状态和 NCI，与较高的 PAA 独立相关。PhenoAge 标志物比生理年龄单独更能区分虚弱（AUROC：0.75[0.66-0.85]比 0.65[0.55-0.77]，p=0.04）。在仅针对 HIV 阳性者的分析中，PhenoAge 单独预测虚弱的效果优于生理年龄单独预测（AUROC：0.7412 比 0.6499，p=0.09）和 VACS 指数（AUROC：0.7412 比 0.6811，p=0.34），尽管差异无统计学意义。 结论：尽管我们的队列中 HIV 阳性者似乎没有加速衰老，但表型衰老标志物与全身炎症、虚弱和心血管疾病危险因素显著相关。这种简单的衰老标志物可用于在相似的生理年龄组内识别高风险的 HIV 阳性者。
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