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

Win Min Han; Hossain M S Sazzad; Mark Bloch; David A Baker; Norman Roth; Ellen Bowden-Reid; Don E Smith; Jennifer F Hoy; Ian Woolley; Robert Finlayson; David J Templeton; Gail V Matthews; Jane Costello; Mark A Dawson; Sarah-Jane Dawson; Mark N Polizzotto; Kathy Petoumenos; Paul Yeh; Nila J Dharan; ARCHIVE Study Group

doi:10.1016/j.xcrm.2024.101835

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

Cell Rep Med. 2024 Dec 17;5(12):101835. doi: 10.1016/j.xcrm.2024.101835. Epub 2024 Dec 2.

Authors

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

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
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.

MeSH terms

Aged
Aged, 80 and over
Aging* / genetics
Clonal Hematopoiesis* / genetics
Cohort Studies
Female
Frailty / genetics
HIV Infections* / genetics
HIV Infections* / virology
Humans
Male
Middle Aged
Mutation / genetics
Quality of Life