TY - JOUR
T1 - Clonal hematopoiesis of indeterminate potential in persons with HIV
AU - Knudsen, Andreas D.
AU - Eskelund, Christian Winther
AU - Benfield, Thomas
AU - Zhao, Yanan
AU - Gelpi, Marco
AU - Køber, Lars
AU - Trøseid, Marius
AU - Kofoed, Klaus F.
AU - Ostrowski, Sisse R.
AU - Reilly, Cavan
AU - Borges, Álvaro H.
AU - Grønbæk, Kirsten
AU - Nielsen, Susanne D.
N1 - Publisher Copyright:
© 2024 Lippincott Williams and Wilkins. All rights reserved.
PY - 2024/3/15
Y1 - 2024/3/15
N2 - 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 with HIV (PWH).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 at least 2%. CAD was categorized according to the most severe coronary artery lesion on coronary computed tomography (CT) angiography as no coronary atherosclerosis; any atherosclerosis defined as at least 1% stenosis and obstructive CAD defined as at least 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.Conclusion:In older, well treated, Scandinavian PWH, 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.
AB - 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 with HIV (PWH).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 at least 2%. CAD was categorized according to the most severe coronary artery lesion on coronary computed tomography (CT) angiography as no coronary atherosclerosis; any atherosclerosis defined as at least 1% stenosis and obstructive CAD defined as at least 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.Conclusion:In older, well treated, Scandinavian PWH, 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.
KW - HIV
KW - atherosclerosis
KW - clonal haematopoiesis
KW - clonal hematopoiesis of indeterminate potential
KW - coronary artery disease
KW - inflammation
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U2 - 10.1097/QAD.0000000000003788
DO - 10.1097/QAD.0000000000003788
M3 - Article
C2 - 37976039
AN - SCOPUS:85186525390
SN - 0269-9370
VL - 38
SP - 487
EP - 495
JO - AIDS
JF - AIDS
IS - 4
ER -