Observational Study

. 2024 Dec 17;5(12):101835.

doi: 10.1016/j.xcrm.2024.101835. Epub 2024 Dec 2.

Age-related clonal hematopoiesis and HIV infection are associated with geriatric outcomes: The ARCHIVE study

Win Min Han¹, Hossain M S Sazzad², Mark Bloch³, David A Baker⁴, Norman Roth⁵, Ellen Bowden-Reid², Don E Smith⁶, Jennifer F Hoy⁷, Ian Woolley⁸, Robert Finlayson⁹, David J Templeton¹⁰, Gail V Matthews¹¹, Jane Costello¹², Mark A Dawson¹³, Sarah-Jane Dawson¹³, Mark N Polizzotto¹⁴, Kathy Petoumenos², Paul Yeh¹⁵, Nila J Dharan¹⁶; ARCHIVE Study Group

Collaborators, Affiliations

Collaborators

Affiliations

¹ Kirby Institute, University of New South Wales Sydney, Sydney, NSW 2033, Australia. Electronic address: wmhan@kirby.unsw.edu.au.
² Kirby Institute, University of New South Wales Sydney, Sydney, NSW 2033, Australia.
³ Kirby Institute, University of New South Wales Sydney, Sydney, NSW 2033, Australia; Holdsworth House Medical Practice, Sydney, NSW 2010, Australia.
⁴ East Sydney Doctors, Sydney, NSW 2010, Australia.
⁵ Prahran Market Clinic, Melbourne, VIC 3181, Australia.
⁶ Albion Centre, South Eastern Sydney Local Health District, Sydney, NSW 2010, Australia; School of Population Health, University of New South Wales Sydney, Sydney, NSW 2033, Australia.
⁷ Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, VIC 3004, Australia.
⁸ Monash Infectious Diseases, Monash Health, Clayton, VIC 3168, Australia; Centre for Inflammatory Diseases, Monash University, Clayton, VIC 3168, Australia.
⁹ Taylor Square Private Clinic, Darlinghurst, NSW 2010, Australia.
¹⁰ Department of Sexual Health Medicine and Sexual Assault Medical Service, Sydney Local Health District, Sydney, NSW 2050, Australia; Discipline of Medicine, Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2050, Australia.
¹¹ Kirby Institute, University of New South Wales Sydney, Sydney, NSW 2033, Australia; St Vincent's Hospital, Darlinghurst, NSW 2010, Australia.
¹² Positive Life NSW, Sydney, NSW 2010, Australia.
¹³ Peter MacCallum Cancer Centre, Melbourne, VIC 3052, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC 3052, Australia; Centre for Cancer Research, University of Melbourne, Melbourne, VIC 3052, Australia.
¹⁴ Kirby Institute, University of New South Wales Sydney, Sydney, NSW 2033, Australia; Australian National University, Canberra, ACT 2601, Australia.
¹⁵ Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia; Monash Haematology, Monash Health, Clayton, VIC 3168, Australia.
¹⁶ Kirby Institute, University of New South Wales Sydney, Sydney, NSW 2033, Australia. Electronic address: ndharan@kirby.unsw.edu.au.

PMID: 39626674
PMCID: PMC11722090
DOI: 10.1016/j.xcrm.2024.101835

Observational Study

Age-related clonal hematopoiesis and HIV infection are associated with geriatric outcomes: The ARCHIVE study

Win Min Han et al. Cell Rep Med. 2024.

. 2024 Dec 17;5(12):101835.

doi: 10.1016/j.xcrm.2024.101835. Epub 2024 Dec 2.

Authors

Collaborators

Affiliations

¹ Kirby Institute, University of New South Wales Sydney, Sydney, NSW 2033, Australia. Electronic address: wmhan@kirby.unsw.edu.au.
² Kirby Institute, University of New South Wales Sydney, Sydney, NSW 2033, Australia.
³ Kirby Institute, University of New South Wales Sydney, Sydney, NSW 2033, Australia; Holdsworth House Medical Practice, Sydney, NSW 2010, Australia.
⁴ East Sydney Doctors, Sydney, NSW 2010, Australia.
⁵ Prahran Market Clinic, Melbourne, VIC 3181, Australia.
⁶ Albion Centre, South Eastern Sydney Local Health District, Sydney, NSW 2010, Australia; School of Population Health, University of New South Wales Sydney, Sydney, NSW 2033, Australia.
⁷ Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, VIC 3004, Australia.
⁸ Monash Infectious Diseases, Monash Health, Clayton, VIC 3168, Australia; Centre for Inflammatory Diseases, Monash University, Clayton, VIC 3168, Australia.
⁹ Taylor Square Private Clinic, Darlinghurst, NSW 2010, Australia.
¹⁰ Department of Sexual Health Medicine and Sexual Assault Medical Service, Sydney Local Health District, Sydney, NSW 2050, Australia; Discipline of Medicine, Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2050, Australia.
¹¹ Kirby Institute, University of New South Wales Sydney, Sydney, NSW 2033, Australia; St Vincent's Hospital, Darlinghurst, NSW 2010, Australia.
¹² Positive Life NSW, Sydney, NSW 2010, Australia.
¹³ Peter MacCallum Cancer Centre, Melbourne, VIC 3052, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC 3052, Australia; Centre for Cancer Research, University of Melbourne, Melbourne, VIC 3052, Australia.
¹⁴ Kirby Institute, University of New South Wales Sydney, Sydney, NSW 2033, Australia; Australian National University, Canberra, ACT 2601, Australia.
¹⁵ Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia; Monash Haematology, Monash Health, Clayton, VIC 3168, Australia.
¹⁶ Kirby Institute, University of New South Wales Sydney, Sydney, NSW 2033, Australia. Electronic address: ndharan@kirby.unsw.edu.au.

PMID: 39626674
PMCID: PMC11722090
DOI: 10.1016/j.xcrm.2024.101835

Abstract

While HIV infection and clonal hematopoiesis (CH) have been linked with inflammatory dysregulation and an increased risk of aging-related comorbidities, their relationship with clinical geriatric syndromes has not been well defined. In the Age-related Clonal Haematopoiesis in an HIV Evaluation Cohort (ARCHIVE) study (NCT04641013), we measure associations between HIV and CH and geriatric syndromes. Of 345 participants (176 with HIV and 169 without HIV), 23% had at least one mutation associated with CH: 27% with HIV and 18% without HIV (p = 0.048). In adjusted analyses, HIV infection is independently associated with increased phenotypic age acceleration (coefficient 1.73, 95% confidence interval [CI] 0.3, 3.16) and CH is independently associated with being frail (vs. pre-frail/robust; odds ratio 2.38, 95% CI 1.01, 5.67) and with having reduced quality of life (coefficient -2.18, 95% CI -3.92, -0.44). Our findings suggest that HIV is associated with increased biological age and that CH may be used as a biomarker for adverse geriatric outcomes.

Keywords: HIV; aging-related comorbidities; clonal hematopoiesis; frailty; geriatric syndromes; multimorbidity; phenotypic age acceleration; quality of life.

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Conflict of interest statement

Declaration of interests M.B. has received funding from Gilead Sciences and ViiV Healthcare for lecturing and traveling to scientific meetings and medical advisory boards. D.A.B. has received funding and travel grants from and served on advisory boards for ViiV Healthcare and Gilead. D.E.S. has received consultancy fees and lecturing honorarium from ViiV Healthcare and Gilead Sciences. J.F.H.’s institution has received reimbursement for her participation in advisory boards for Gilead Sciences and ViiV Healthcare. I.W.’s institution has received financial or in-kind support for his role in clinical studies from Moderna, CSL, MSD, Gilead, and ViiV. G.V.M. has received research funding from Gilead, AbbVie, Janssen, and ViiV, has served on advisory boards for AstraZeneca and ViiV, and has provided consultancy and received travel support from Gilead. M.N.P. has received research funding from ViiV, Janssen, and Gilead (awarded to institution), research support (in kind) from ViiV, Janssen, BMS, Verastem, ASTEX, Grifols, CSL Behring, Takeda, and Emergent (in kind, to institution) and has served on the advisory board for AstraZeneca and Gilead. P.Y. has received speaker honoraria from Astellas Pharma for unrelated projects.

Figures

**Figure 1**
Study recruitment and loss to follow-up

**Figure 2**
Associations between clonal hematopoiesis, HIV infection, and primary geriatric outcomes The reference line (Ref) represents an odds ratio of 1 (no effect) or a coefficient of 0 (no effect). Data are presented as odds ratios and 95% confidence intervals (CI) or coefficients and 95% CI. Logistic regression was used to calculate the adjusted odds ratio for the outcomes: frailty (A) and multimorbidity (B). Linear regression was used to calculate the adjusted coefficients for PAA (C) and QoL (D). (A) For frailty, we adjusted for the presence of any CH mutation, age group, and HIV status. (B) For multimorbidity, we adjusted for the presence of any CH mutation, age group, gender, HIV status, BMI, smoking status, sexual orientation, and inflammatory markers (hs-CRP and IL-6). (C) For PAA, we adjusted for the presence of any CH mutation, HIV status, gender, sexual orientation, BMI, and smoking status. (D) For QoL, we adjusted for the presence of any CH mutation, age group, HIV status, gender, sexual orientation, BMI, smoking status, frailty, and ADL and IADL dependency. Abbreviations: CH, clonal hematopoiesis; PAA, phenotypic age acceleration; QoL, quality of life; hs-CRP, high-sensitive C-reactive protein; IL-6, interleukin-6; ADL, activities of daily living; IADL, instrumental activities of daily living.

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References

1. World Health Organization. Ageing and Health. Available at: https://www.who.int/news-room/fact-sheets/detail/ageing-and-health. Access date May 7, 2024.
1. World Health Organization. UN Decade of Healthy Ageing. Available at: https://www.who.int/initiatives/decade-of-healthy-ageing. Access date May 7, 2024.
1. Li N., Liu G., Gao H., Wu Q., Meng J., Wang F., Jiang S., Chen M., Xu W., Zhang Y., et al. Geriatric syndromes, chronic inflammation, and advances in the management of frailty: A review with new insights. Biosci. Trends. 2023;17:262–270. doi: 10.5582/bst.2023.01184. - DOI - PubMed
1. Lopez-Candales A., Hernández Burgos P.M., Hernandez-Suarez D.F., Harris D. Linking Chronic Inflammation with Cardiovascular Disease: From Normal Aging to the Metabolic Syndrome. J. Nat. Sci. 2017;3 - PMC - PubMed
1. Shacter E., Weitzman S.A. Chronic inflammation and cancer. Oncology (Williston Park, NY) 2002;16:217–232. 229; discussion 230. - PubMed

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Age-related clonal hematopoiesis and HIV infection are associated with geriatric outcomes: The ARCHIVE study

Collaborators

Affiliations

Age-related clonal hematopoiesis and HIV infection are associated with geriatric outcomes: The ARCHIVE study

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical