Risk factors for clonal hematopoiesis of indeterminate potential in people with HIV: a report from the REPRIEVE trial.

Abstract

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. 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.

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Published Version (Please cite this version)

10.1182/bloodadvances.2023011324

Publication Info

Bhattacharya, Romit, Md Mesbah Uddin, Aniruddh P Patel, Abhishek Niroula, Phoebe Finneran, Rachel Bernardo, Kathleen V Fitch, Michael T Lu, et al. (2024). Risk factors for clonal hematopoiesis of indeterminate potential in people with HIV: a report from the REPRIEVE trial. Blood advances, 8(4). pp. 959–967. 10.1182/bloodadvances.2023011324 Retrieved from https://hdl.handle.net/10161/30205.

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Bloomfield

Gerald Bloomfield

Associate Professor of Medicine

Gerald Bloomfield, MD, MPH, joined the faculty in Medicine and Global Health after completing his Cardiovascular Medicine fellowship training at Duke University Medical Center and Duke Clinical Research Institute. Bloomfield also completed the Duke Global Health Residency/Fellowship Pathway and a Fogarty International Clinical Research Fellowship. He received his medical education, internal medicine residency and Master of Public Health degree from Johns Hopkins University. Bloomfield leads a longstanding research and capacity building program on cardiovascular global health which includes work in under-resourced communities in the US and a number of low- and middle-income country settings.


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