HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults

Dharan, NJ; Yeh, P; Bloch, M; Yeung, MM; Baker, D; Guinto, J; Roth, N; Ftouni, S; Ognenovska, K; Smith, D; Hoy, JF; Woolley, I; Pell, C; Templeton, DJ; Fraser, N; Rose, N; Hutchinson, J; Petoumenos, K; Dawson, SJ; Polizzotto, MN; Dawson, MA; The ARCHIVE Study Group

Author(s): Dharan, NJ; Yeh, P; Bloch, M; Yeung, MM; Baker, D; Guinto, J; Roth, N; Ftouni, S; Ognenovska, K; Smith, D; Hoy, JF; Woolley, I; Pell, C; Templeton, DJ; Fraser, N; Rose, N; Hutchinson, J; Petoumenos, K; Dawson, SJ; Polizzotto, MN; Dawson, MA; The ARCHIVE Study Group;
Details: Publication Year 2021-06,Volume 27,Issue #6,Page 1006-1011
Journal Title: Nature Medicine
Publication Type: Research article
Abstract: People with human immunodeficiency virus (HIV) have higher rates of certain comorbidities, particularly cardiovascular disease and cancer, than people without HIV(1-5). In view of observations that somatic mutations associated with age-related clonal hematopoiesis (CH) are linked to similar comorbidities in the general population(6-10), we hypothesized that CH may be more prevalent in people with HIV. To address this issue, we established a prospective cohort study, the ARCHIVE study (NCT04641013), in which 220 HIV-positive and 226 HIV-negative participants aged 55 years or older were recruited in Australia. Demographic characteristics, clinical data and peripheral blood were collected to assess the presence of CH mutations and to identify potential risk factors for and clinical sequelae of CH. In total, 135 CH mutations were identified in 100 (22.4%) of 446 participants. CH was more prevalent in HIV-positive participants than in HIV-negative participants (28.2% versus 16.8%, P = 0.004), overall and across all age groups; the adjusted odds ratio for having CH in those with HIV was 2.16 (95% confidence interval 1.34-3.48, P = 0.002). The most common genes mutated overall were DNMT3A (47.4%), TET2 (20.0%) and ASXL1 (13.3%). CH and HIV infection were independently associated with increases in blood parameters and biomarkers associated with inflammation. These data suggest a selective advantage for the emergence of CH in the context of chronic infection and inflammation related to HIV infection.
Keywords: Aged; Aging/genetics/pathology; Cardiovascular Diseases/complications/epidemiology/*genetics/virology; Clonal Hematopoiesis/genetics; DNA (Cytosine-5-)-Methyltransferases/*genetics; DNA Methyltransferase 3A; DNA-Binding Proteins/*genetics; Dioxygenases; Female; HIV/pathogenicity; HIV Infections/complications/epidemiology/*genetics/virology; Humans; Inflammation/genetics/pathology/virology; Male; Middle Aged; Mutation/genetics; Neoplasms/complications/epidemiology/genetics/virology; Proto-Oncogene Proteins/*genetics; Repressor Proteins/*genetics
Department(s): Laboratory Research; Haematology; Medical Oncology
PubMed ID: 34099923
Publisher's Version: https://doi.org/10.1038/s41591-021-01357-y
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-01-30 05:59:55

Last Modified: 2026-01-30 06:01:39