{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T04:51:35Z","timestamp":1777956695731,"version":"3.51.4"},"posted":{"date-parts":[[2026,2,9]]},"group-title":"Cardiovascular Medicine","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Clonal hematopoiesis of indeterminate potential (CHIP) is associated with cardiovascular disease (CVD) in the general population and is more common among people with HIV (PWH). The mechanisms by which CHIP contributes to atherosclerosis in PWH are unknown. We hypothesized that CHIP is associated with carotid atherosclerosis and arterial inflammation among PWH.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    In a cohort study, we studied PWH ages 31-74 years with treated, suppressed HIV. CHIP mutations were detected with a validated targeted sequencing assay. Carotid intima-media thickness (IMT) was measured longitudinally with ultrasound. Aortic inflammation and lymph node activity were assessed cross-sectionally using\n                    <jats:sup>18<\/jats:sup>\n                    F-FDG-PET. Inflammatory biomarkers were measured using multiplex electrochemiluminescence assay. Linear regression was employed, with adjustments for traditional and HIV-related factors.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We included 230 PWH (52\u00b19 years, 7% female); 32 (14%) had CHIP with median variant allele fraction of 2.8%. Common mutations were in DNM3TA (n=21) and TET2 (n=6). Age was associated with CHIP (OR 2.0 per decade older, 95% CI 1.3-3.01; p=0.002). Among 166 participants with IMT measurements (CHIP=23), CHIP was not associated with IMT (p=0.21; unchanged after adjustment). Among 80 with FDG-PET, CHIP (n=12) was not associated with arterial inflammation (p=0.89), but was associated with higher lymph node metabolic activity (p=0.017) that was attenuated in reference to background activity and adjusted for risk factors. CHIP was not associated with soluble inflammatory markers or viral persistence markers.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Among PWH, CHIP mutations were not associated with subclinical atherosclerosis, arterial inflammation, or soluble inflammatory markers but may be related to lymph node metabolic activity. The mechanism by which CHIP increases HIV-associated atherosclerosis may preferentially involve lymph nodes and merits additional evaluation.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec id=\"s4c\">\n                  <jats:title>Visual Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" fig-type=\"figure\" orientation=\"portrait\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"26345712v2_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                  <jats:p>\n                    <jats:bold>Visual Abstract Legend:<\/jats:bold>\n                    We hypothesized that clonal hematopoeiesis of indeterminate potential (CHIP) may be a mediator of the association between HIV and atherosclerosis; we investigated this hypothesis by measuring CHIP mutations in human blood samples from people with HIV (PWH) and determining whether CHIP mutations were associated with carotid intima media thickness assessed using ultrasound (longitudinal, n=166) and aortic inflammation using\n                    <jats:sup>18<\/jats:sup>\n                    F-FDG-PET-CT (cross-sectional, n=80). In our study of 230 PWH (32 with CHIP), we did not find evidence for an association between the presence of any CHIP mutation and either carotid atherosclerosis or arterial inflammation.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Condensed Abstract<\/jats:title>\n                  <jats:p>People with HIV (PWH) ave increased risk of clonal hematopoiesis of indeterminate potential (CHIP) and atherosclerosis, but whether clonal hematopoiesis accelerates atherosclerosis among PWH is unknown. We hypothesized that CHIP is associated with carotid atherosclerosis and arterial inflammation among PWH. In a cohort study that conducted longitudinal carotid ultrasound and 18F-FDG-PET, we studied PWH ages 31-74 years with treated, suppressed HIV. We measured CHIP mutations with a validated targeted sequencing assay. We included 230 PWH (52+9 years, 7% female); 32 (14%) had CHIP (66% DNMT3A) with median variant allele fraction of 2.8%. Overall, CHIP was not associated with carotid intima media thickness or arterial inflammation assessed with FDG PET. CHIP was associated with increased lymph node metabolic activity, a hypothesis-generating finding. Among PWH, CHIP was not associated with markers of subclinical atherosclerosis.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.05.26345712","type":"posted-content","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T02:50:32Z","timestamp":1770691832000},"source":"Crossref","is-referenced-by-count":0,"title":["Clonal Hematopoiesis in HIV and Atherosclerosis, Arterial Inflammation, and Lymph Node Metabolic Activity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7612-3352","authenticated-orcid":false,"given":"Matthew S.","family":"Durstenfeld","sequence":"first","affiliation":[{"name":"University of California, Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine J.","family":"Kentoffio","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra E.","family":"Teng","sequence":"additional","affiliation":[{"name":"Kaiser Permanente, Oakland, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-8881","authenticated-orcid":false,"given":"Shady","family":"Abohashem","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danny","family":"Li","sequence":"additional","affiliation":[{"name":"University of California, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifei","family":"Ma","sequence":"additional","affiliation":[{"name":"University of California, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5112-4220","authenticated-orcid":false,"given":"Rebecca","family":"Hoh","sequence":"additional","affiliation":[{"name":"University of California, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6371-747X","authenticated-orcid":false,"given":"Steven G.","family":"Deeks","sequence":"additional","affiliation":[{"name":"University of California, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5824-9595","authenticated-orcid":false,"given":"Alexander G.","family":"Bick","sequence":"additional","affiliation":[{"name":"Vanderbilt University, Nashville, TN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9211-5483","authenticated-orcid":false,"given":"Ahmed A.","family":"Tawakol","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3427-6043","authenticated-orcid":false,"given":"Priscilla Y.","family":"Hsue","sequence":"additional","affiliation":[{"name":"University of California, Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026050420351442000_2026.02.05.26345712v2.1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.033369"},{"key":"2026050420351442000_2026.02.05.26345712v2.2","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.idc.2024.04.006","article-title":"Advances in the Management of Cardiovascular Disease in the Setting of Human Immunodeficiency Virus","volume":"38","year":"2024","journal-title":"Infect Dis Clin North Am"},{"key":"2026050420351442000_2026.02.05.26345712v2.3","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000001149"},{"key":"2026050420351442000_2026.02.05.26345712v2.4","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000954"},{"key":"2026050420351442000_2026.02.05.26345712v2.5","doi-asserted-by":"crossref","unstructured":"Oren O , Small AM , Libby P. 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