HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults
Autor: | Miriam M. Yeung, Sarah-Jane Dawson, Sarah Ftouni, Don Smith, Nila J. Dharan, David Baker, Mark Bloch, Jolie Hutchinson, Neil Fraser, Nectarios Rose, Catherine Pell, Kathy Petoumenos, Mark A. Dawson, Jennifer F Hoy, Ian Woolley, Paul Yeh, Mark N. Polizzotto, Katherine Ognenovska, David J Templeton, Norman Roth, Jerick Guinto |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
medicine.medical_specialty business.industry Incidence (epidemiology) Context (language use) General Medicine Disease Odds ratio medicine.disease General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Chronic infection 030104 developmental biology 0302 clinical medicine Clinical research Acquired immunodeficiency syndrome (AIDS) 030220 oncology & carcinogenesis Internal medicine Medicine business Prospective cohort study |
Zdroj: | Nature Medicine. 27:1006-1011 |
ISSN: | 1546-170X 1078-8956 |
Popis: | People with human immunodeficiency virus (HIV) have higher rates of certain comorbidities, particularly cardiovascular disease and cancer, than people without HIV1–5. In view of observations that somatic mutations associated with age-related clonal hematopoiesis (CH) are linked to similar comorbidities in the general population6–10, 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. In a prospective cohort study, HIV-positive participants have a higher incidence of clonal hematopoiesis than HIV-negative ones, implicating clonal hematopoiesis in the increased risks of individuals with HIV for malignancy and cardiovascular disease. |
Databáze: | OpenAIRE |
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