ResearchIn-Press PreviewAIDS/HIVAging Open Access | 10.1172/jci.insight.174783
1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
2Translational Stem Cell Biology Branch, National Heart, Lung and Blood Inst, NIH, Bethesda, United States of America
3National Institute of Allergy and Infectious Diseases, NIH, Betehsda, United States of America
4Leidos Biomedical Research Core, Frederick, United States of America
5Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
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1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
2Translational Stem Cell Biology Branch, National Heart, Lung and Blood Inst, NIH, Bethesda, United States of America
3National Institute of Allergy and Infectious Diseases, NIH, Betehsda, United States of America
4Leidos Biomedical Research Core, Frederick, United States of America
5Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
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1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
2Translational Stem Cell Biology Branch, National Heart, Lung and Blood Inst, NIH, Bethesda, United States of America
3National Institute of Allergy and Infectious Diseases, NIH, Betehsda, United States of America
4Leidos Biomedical Research Core, Frederick, United States of America
5Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
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1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
2Translational Stem Cell Biology Branch, National Heart, Lung and Blood Inst, NIH, Bethesda, United States of America
3National Institute of Allergy and Infectious Diseases, NIH, Betehsda, United States of America
4Leidos Biomedical Research Core, Frederick, United States of America
5Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
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1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
2Translational Stem Cell Biology Branch, National Heart, Lung and Blood Inst, NIH, Bethesda, United States of America
3National Institute of Allergy and Infectious Diseases, NIH, Betehsda, United States of America
4Leidos Biomedical Research Core, Frederick, United States of America
5Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
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1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
2Translational Stem Cell Biology Branch, National Heart, Lung and Blood Inst, NIH, Bethesda, United States of America
3National Institute of Allergy and Infectious Diseases, NIH, Betehsda, United States of America
4Leidos Biomedical Research Core, Frederick, United States of America
5Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
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1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
2Translational Stem Cell Biology Branch, National Heart, Lung and Blood Inst, NIH, Bethesda, United States of America
3National Institute of Allergy and Infectious Diseases, NIH, Betehsda, United States of America
4Leidos Biomedical Research Core, Frederick, United States of America
5Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
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1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
2Translational Stem Cell Biology Branch, National Heart, Lung and Blood Inst, NIH, Bethesda, United States of America
3National Institute of Allergy and Infectious Diseases, NIH, Betehsda, United States of America
4Leidos Biomedical Research Core, Frederick, United States of America
5Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
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1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
2Translational Stem Cell Biology Branch, National Heart, Lung and Blood Inst, NIH, Bethesda, United States of America
3National Institute of Allergy and Infectious Diseases, NIH, Betehsda, United States of America
4Leidos Biomedical Research Core, Frederick, United States of America
5Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
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1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
2Translational Stem Cell Biology Branch, National Heart, Lung and Blood Inst, NIH, Bethesda, United States of America
3National Institute of Allergy and Infectious Diseases, NIH, Betehsda, United States of America
4Leidos Biomedical Research Core, Frederick, United States of America
5Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
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1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
2Translational Stem Cell Biology Branch, National Heart, Lung and Blood Inst, NIH, Bethesda, United States of America
3National Institute of Allergy and Infectious Diseases, NIH, Betehsda, United States of America
4Leidos Biomedical Research Core, Frederick, United States of America
5Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
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1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
2Translational Stem Cell Biology Branch, National Heart, Lung and Blood Inst, NIH, Bethesda, United States of America
3National Institute of Allergy and Infectious Diseases, NIH, Betehsda, United States of America
4Leidos Biomedical Research Core, Frederick, United States of America
5Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
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1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
2Translational Stem Cell Biology Branch, National Heart, Lung and Blood Inst, NIH, Bethesda, United States of America
3National Institute of Allergy and Infectious Diseases, NIH, Betehsda, United States of America
4Leidos Biomedical Research Core, Frederick, United States of America
5Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
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1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
2Translational Stem Cell Biology Branch, National Heart, Lung and Blood Inst, NIH, Bethesda, United States of America
3National Institute of Allergy and Infectious Diseases, NIH, Betehsda, United States of America
4Leidos Biomedical Research Core, Frederick, United States of America
5Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
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1National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America
2Translational Stem Cell Biology Branch, National Heart, Lung and Blood Inst, NIH, Bethesda, United States of America
3National Institute of Allergy and Infectious Diseases, NIH, Betehsda, United States of America
4Leidos Biomedical Research Core, Frederick, United States of America
5Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
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Published April 2, 2024 - More info
People with HIV (PWH) have a higher age-adjusted mortality due to chronic immune activation and age-related comorbidities. PWH also have higher rates of clonal hematopoiesis (CH) than age-matched non-HIV cohorts, however, risk factors influencing the development and expansion of CH in PWH remain incompletely explored. We investigated the relationship between CH, immune biomarkers, and HIV-associated risk factors (CD4, CD8 T-cells, nadir CD4 count, opportunistic infections [OIs], and immune reconstitution inflammatory syndrome [IRIS]) in a diverse cohort of 197-PWH with median age of 42-years, using a 56-gene panel. Seventy-nine percent had a CD4 nadir < 200, 58.9% had prior OIs, and 34.5% had a history of IRIS. The prevalence of CH was high (27.4%), even in younger individuals, and CD8 T-cells and nadir CD4 counts strongly associated with CH after controlling for age. A history of IRIS was associated with CH in a subgroup analysis of ≥ 35-years-old patients. Inflammatory biomarkers were higher in CH carriers compared to non-carriers supporting a dysregulated immune state. These findings suggest PWH with low nadir CD4 and/or inflammatory complications may be at high risk of CH regardless of age and represent a high-risk group that could benefit from risk reduction and potentially targeted immunomodulation.