Blood Adv. 2024 Jan 10:bloodadvances.2023011324. doi: 10.1182/bloodadvances.2023011324. Online ahead of print.

ABSTRACT

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 (WES). 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 4,486 PWH, mean (SD) age was 49.9 (6.4) years, 1650 (36.8%) were female, and 3418 (76.2%) were non-White. CHIP was identified in 223/4486 (4.97%), and in 38/373 (10.2%) among those 60 years of age or older. Age (OR 1.07, 95%CI 1.05-1.09, p<0.0001) and smoking (OR 1.37, 95%CI 1.14-1.66, p<0.001) 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=0.0019), South Asia (OR 0.45, 95%CI 0.23-0.80, p=0.01), and Latin America/Caribbean (OR 0.56, 95%CI 0.34-0.87, p=0.014). Hispanic/Latino ethnicity (OR 0.38, 95%CI 0.23-0.54, p=0.002) 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=0.006) 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=0.005) (pinteraction=0.0492). 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. Clinical Trials Registration: NCT02344290.

PMID:38197863 | DOI:10.1182/bloodadvances.2023011324