Clonal hematopoiesis of indeterminate potential in persons with HIV

Abstract

Background: Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with older age, inflammation and with risk of coronary artery disease (CAD). We aimed to characterize the burden of CHIP, and to explore the association between CHIP, inflammatory markers, and CAD in older persons living with HIV (PLWH). Methods: From the Copenhagen Comorbidity in HIV Infection (COCOMO) study, we included 190 individuals older than 55 years of age. We defined CHIP as variant allele fraction ≥ 2%. CAD was categorized according to the most severe coronary artery lesion on coronary CT angiography as 1) no coronary atherosclerosis; 2) any atherosclerosis defined as ≥1% stenosis, and 3) obstructive CAD defined as ≥50% stenosis. Results: In the entire population (median age 66 years, 87% men), we identified a total of 62 mutations distributed among 49 (26%) participants. The three most mutated genes were DNMT3A, TET2, and ASXL1, accounting for 49%, 25%, and 16% of mutations, respectively. Age and sex were the only variables associated with CHIP. IL-1β, IL-1Ra, IL-2, IL-6, IL-10, soluble CD14, soluble CD163 and TNF-α were not associated with CHIP and CHIP was not associated with any atherosclerosis or with obstructive CAD in adjusted analyses. Conclusions: In older, well-treated, Scandinavian PLWH, more than one in four had at least one CHIP mutation. We did not find evidence of an association between CHIP and inflammatory markers or between CHIP and CAD. CHIP is an unlikely underlying mechanism to explain the association between inflammation and CAD in treated HIV disease.