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Cited by 108Acute Myeloid Leukemia ResearchHIV-related health complications and treatmentsHIV Research and Treatment

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

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Dharan, Nila J., Yeh, Paul, Bloch, Mark, Yeung, Miriam M., Baker, David, Guinto, Jerick, Roth, Norman, Ftouni, Sarah +23 more·2021·Nature Medicine
DOI 10.1038/s41591-021-01357-y

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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.

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  • Multivariable analysis of adults with HIV-positive status, associated with elevated plasma IL-6 levels, demonstrates increased prevalence of CH with DNMT3A, TET2, and ASXL1 variants.

    “Multivariable analysis of adults with HIV-positive status, which is associated with elevated plasma IL-6 levels, demonstrated increased prevalence of CH with DNMT3A, TET2, and ASXL1 variants [59].”

    From Clonal hematopoiesis and inflammation – the perpetual cycle (2023) · cites this paper as [59]

    The Association between HIV infection and the presence of clonal haematopoiesis mutations section reports higher adjusted odds of CH in HIV-positive adults, and Identification of clonal haematopoiesis mutations reports a higher proportion of DNMT3A, TET2 and ASXL1 mutations in that group. The adjusted result is for CH overall, not separately for each gene. The IL6R polymorphism section describes elevated serum IL-6, rather than the claimed plasma IL-6. (LLM, conf=0.85)

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Authors
Dharan, N. J., Yeh, P., Bloch, M., Yeung, M. M., Baker, D., Guinto, J., Roth, N., Ftouni, S., Ognenovska, K., Smith, D., Hoy, J. F., Woolley, I., Pell, C., Templeton, D. J., Fraser, N., Rose, N., Hutchinson, J., Petoumenos, K., Dawson, S.-J., Polizzotto, M. N., Dawson, M. A., The ARCHIVE Study Group, Vincent, T., Rosario, R., Lau, H., Smith, D., Price, S., O’Brien, J., Tan, H. T. L., Sinclair, B., & Bascombe, F.
Affiliations
  • UNSW Sydney (AU)
  • The University of Melbourne (AU)
  • Holdsworth House Medical Practice (AU)
  • Peter MacCallum Cancer Centre (AU)
  • The Alfred Hospital (AU)
  • Monash Medical Centre (AU)
  • The University of Sydney (AU)
  • Monash Health (AU)
  • Sydney Local Health District (AU)
  • St Vincent's Hospital Sydney (AU)
Corresponding author
  • Petoumenos, Kathy
  • Dawson, Sarah-Jane
  • Polizzotto, Mark N.
  • Dawson, Mark A.
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2021-06
Volume
27
Issue
6
Pages
1006-1011
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-021-01357-y
OpenAlex
W3171852307
Cited by
108
References
8
Citations by year
2026: 14 · 2025: 14 · 2024: 13 · 2023: 22 · 2022: 33 · 2021: 11
FWCI
12.93
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Medicine (publishedVersion)
  • medRxiv (acceptedVersion)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Department of Health | National Health and Medical Research Council (1196749, 1128984, Post graduate scholarship, 1195030, 1196755, 1110067, 1213110)
  • Cancer Council Victoria (Dunlop Fellowship)
  • Howard Hughes Medical Institute (International research scholarship)
  • Snowdome/Maddie Riewoldt’s Vision FellowshipGilead Fellowship
  • CSL Centenary fellowship
  • Cancer Institute of NSW Future Research Leader Fellowship
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Health Sciences › Medicine › Emergency Medicine › HIV-related health complications and treatments
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Keywords
HIV infection, age-related clonal hematopoiesis, somatic mutations, DNMT3A, TET2, ASXL1, chronic inflammation, cardiovascular risk, cancer risk, older adults
MeSH terms
Clonal Hematopoiesis, DNA Methyltransferase 3A, Aged, Aging, Cardiovascular Diseases, DNA (Cytosine-5-)-Methyltransferases, DNA-Binding Proteins, Female, HIV, Humans, Inflammation, Male, Middle Aged, Mutation, Neoplasms, Proto-Oncogene Proteins, Repressor Proteins, HIV Infections, Dioxygenases

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