Levy Matthew E, Greenberg Alan E, Magnus Manya, Younes Naji, Castel Amanda
Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Washington, District of Columbia.
AIDS Res Hum Retroviruses. 2019 Jan;35(1):81-91. doi: 10.1089/AID.2018.0145. Epub 2018 Nov 27.
To explore reasons for the disproportionate metabolic and cardiovascular disease burdens among older HIV-infected persons, we investigated whether associations of CD4 count and HIV viral load (VL) with non-high-density lipoprotein cholesterol (non-HDL-C) and high-density lipoprotein cholesterol [HDL-C] differed by age. Longitudinal clinical and laboratory data were collected between 2011 and 2016 for HIV-infected outpatients in the DC Cohort study. Using data for patients aged ≥21 years with ≥1 cholesterol result and contemporaneous CD4/VL results, we created multivariable linear regression models with generalized estimating equations. Among 3,912 patients, the median age was 50 years, 78% were male, 76% were non-Hispanic black, 93% were using antiretroviral therapy, 8% had a CD4 count <200 cells/μL, and 18% had an HIV VL ≥200 copies/mL. Overall, CD4 count <200 (vs. >500) cells/μL and VL ≥200 copies/mL were associated with lower non-HDL-C concentrations (p < .01), but associations were more positive with increasing age (CD4-age/VL-age interactions, p < .01). CD4 count <200 cells/μL was associated with lower non-HDL-C among patients aged <50 years [β = -7.8 mg/dL (95% confidence interval, CI: -13.2 to -2.4)] but higher non-HDL-C among patients aged 60-69 years [β = +8.1 mg/dL (95% CI: 0.02-16.2)]. VL ≥200 copies/mL was associated with lower non-HDL-C among patients aged <50 years [β = -3.3 mg/dL (95% CI: -6.7 to 0.1)] but higher non-HDL-C among patients aged ≥70 years [β = +16.0 mg/dL (95% CI: -1.4 to 33.3)], although precision was reduced in age-stratified analyses. Although no age differences were detected for HDL-C, VL ≥200 copies/mL was more strongly associated with lower HDL-C concentrations when CD4 count was <200 cells/μL [β = -7.0 mg/dL (95% CI: -9.7 to -4.3)] versus 200-500 cells/μL [β = -4.2 (95% CI: -5.9 to -2.6)] or >500 cells/μL [β = -2.2 (95% CI: -3.7 to -0.8)] (CD4-VL interaction, p < .01). We detected a novel age-modified relationship between immunosuppression and viremia and atherogenic cholesterol patterns. These findings may contribute to our understanding of the high risk of dyslipidemia observed among persons aging with HIV.
为探究老年HIV感染者代谢和心血管疾病负担过重的原因，我们调查了CD4细胞计数和HIV病毒载量（VL）与非高密度脂蛋白胆固醇（non-HDL-C）和高密度脂蛋白胆固醇（HDL-C）之间的关联是否因年龄而异。在DC队列研究中，收集了2011年至2016年期间HIV感染门诊患者的纵向临床和实验室数据。利用年龄≥21岁、有≥1次胆固醇检测结果以及同期CD4/VL检测结果的患者数据，我们创建了带有广义估计方程的多变量线性回归模型。在3912例患者中，年龄中位数为50岁，78%为男性，76%为非西班牙裔黑人，93%正在接受抗逆转录病毒治疗，8%的CD4细胞计数<200个/μL，18%的HIV病毒载量≥200拷贝/mL。总体而言，CD4细胞计数<200（对比>500）个/μL和病毒载量≥200拷贝/mL与较低的非HDL-C浓度相关（p<0.01），但随着年龄增长，这种关联更为正向（CD4-年龄/病毒载量-年龄交互作用，p<0.01）。CD4细胞计数<200个/μL在年龄<50岁的患者中与较低的非HDL-C相关[β=-7.8mg/dL（95%置信区间，CI：-13.2至-2.4）]，但在年龄60 - 69岁的患者中与较高的非HDL-C相关[β=+8.1mg/dL（95%CI：0.02至-16.2）]。病毒载量≥200拷贝/mL在年龄<50岁的患者中与较低的非HDL-C相关[β=-3.3mg/dL（95%CI：-6.7至0.1）]，但在年龄≥70岁的患者中与较高的非HDL-C相关[β=+16.0mg/dL（95%CI：-1.4至33.3）]，尽管在年龄分层分析中精度有所降低。虽然未检测到HDL-C存在年龄差异，但当CD4细胞计数<200个/μL时，病毒载量≥200拷贝/mL与较低的HDL-C浓度的关联更强[β=-7.0mg/dL（95%CI：-9.7至-4.3）]，而CD4细胞计数在200 - 500个/μL时为[β=-4.2（95%CI：-5.9至-2.6）]，CD4细胞计数>500个/μL时为[β=-2.2（95%CI：-3.7至-0.8）]（CD4-病毒载量交互作用，p<0.01）。我们发现了免疫抑制、病毒血症与致动脉粥样硬化胆固醇模式之间一种新的年龄修正关系。这些发现可能有助于我们理解在感染HIV的老年人群中观察到的血脂异常高风险。
