Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.
Department of Medicine, Harvard Medical School, Boston, MA.
Blood Adv. 2024 Feb 27;8(4):959-967. doi: 10.1182/bloodadvances.2023011324.
Clonal hematopoiesis of indeterminate potential (CHIP), the clonal expansion of myeloid cells with leukemogenic mutations, results in increased coronary artery disease (CAD) risk. CHIP is more prevalent among people with HIV (PWH), but the risk factors are unknown. CHIP was identified among PWH in REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) using whole-exome sequencing. Logistic regression was used to associate sociodemographic factors and HIV-specific factors with CHIP adjusting for age, sex, and smoking status. In the studied global cohort of 4486 PWH, mean age was 49.9 (standard deviation [SD], 6.4) years; 1650 (36.8%) were female; and 3418 (76.2%) were non-White. CHIP was identified in 223 of 4486 (4.97%) and in 38 of 373 (10.2%) among those aged ≥60 years. Age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.05-1.09; P < .0001) and smoking (OR, 1.37; 95% CI, 1.14-1.66; P < .001) associated with increased odds of CHIP. Globally, participants outside of North America had lower odds of CHIP including sub-Saharan Africa (OR, 0.57; 95% CI, 0.4-0.81; P = .0019), South Asia (OR, 0.45; 95% CI, 0.23-0.80; P = .01), and Latin America/Caribbean (OR, 0.56; 95% CI, 0.34-0.87; P = .014). Hispanic/Latino ethnicity (OR, 0.38; 95% CI, 0.23-0.54; P = .002) associated with significantly lower odds of CHIP. Among HIV-specific factors, CD4 nadir <50 cells/mm3 associated with a 1.9-fold (95%CI, 1.21-3.05; P = .006) increased odds of CHIP, with the effect being significantly stronger among individuals with short duration of antiretroviral therapy (ART; OR, 4.15; 95% CI, 1.51-11.1; P = .005) (Pinteraction= .0492). Among PWH at low-to-moderate CAD risk on stable ART, smoking, CD4 nadir, North American origin, and non-Hispanic ethnicity associated with increased odds of CHIP. This trial was registered at www.ClinicalTrials.gov as NCT02344290.
不确定潜能的克隆性造血（CHIP），即具有致白血病突变的髓系细胞的克隆性扩张，导致冠状动脉疾病（CAD）风险增加。CHIP 在感染艾滋病毒（HIV）的人群（PWH）中更为普遍，但风险因素尚不清楚。CHIP 是在 REPRIEVE （预防 HIV 血管事件的随机试验）中使用全外显子组测序在 PWH 中发现的。使用逻辑回归将社会人口统计学因素和 HIV 特异性因素与 CHIP 相关联，调整年龄、性别和吸烟状况。在这项研究的全球队列中，4486 名 PWH 的平均年龄为 49.9（标准差[SD]，6.4）岁；1650 名（36.8%）为女性；3418 名（76.2%）为非白人。在 4486 名中，有 223 名（4.97%）和 373 名（10.2%）年龄≥60 岁的人发现了 CHIP。年龄（优势比[OR]，1.07；95%置信区间[CI]，1.05-1.09；P<0.0001）和吸烟（OR，1.37；95%CI，1.14-1.66；P<0.001）与 CHIP 的可能性增加相关。在全球范围内，北美以外的参与者 CHIP 发生率较低，包括撒哈拉以南非洲（OR，0.57；95%CI，0.4-0.81；P=0.0019）、南亚（OR，0.45；95%CI，0.23-0.80；P=0.01）和拉丁美洲/加勒比地区（OR，0.56；95%CI，0.34-0.87；P=0.014）。西班牙裔/拉丁裔种族（OR，0.38；95%CI，0.23-0.54；P=0.002）与 CHIP 发生率显著降低相关。在 HIV 特异性因素中，CD4 最低点<50 个细胞/mm3 与 CHIP 的可能性增加 1.9 倍（95%CI，1.21-3.05；P=0.006），在接受抗逆转录病毒治疗（ART）时间较短的个体中，这种作用明显更强（OR，4.15；95%CI，1.51-11.1；P=0.005）（P 交互=0.0492）。在稳定接受 ART 的低至中度 CAD 风险的 PWH 中，吸烟、CD4 最低点、北美血统和非西班牙裔种族与 CHIP 的可能性增加相关。该试验在 www.ClinicalTrials.gov 上注册为 NCT02344290。
