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

Nila J Dharan1, Paul Yeh2,3, Mark Bloch4, Miriam M Yeung2,3, David Baker5, Jerick Guinto2, Norman Roth6, Sarah Ftouni2, Katherine Ognenovska1, Don Smith7,8, Jennifer F Hoy9, Ian Woolley10,11, Catherine Pell12, David J Templeton1,13,14, Neil Fraser15, Nectarios Rose1, Jolie Hutchinson1, Kathy Petoumenos16, Sarah-Jane Dawson17,18,19, Mark N Polizzotto20,21, Mark A Dawson22,23,24, ARCHIVE Study Group

  1. Kirby Institute, University of New South Wales Sydney, Sydney, New South Wales, Australia.
  2. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  3. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
  4. Holdsworth House Medical Practice, Sydney, New South Wales, Australia.
  5. East Sydney Doctors, Darlinghurst, New South Wales, Australia.
  6. Prahran Market Clinic, Melbourne, Victoria, Australia.
  7. Albion Centre, South Eastern Sydney Local Hospital Network, Sydney, New South Wales, Australia.
  8. School of Public Health and Community Medicine, University of New South Wales Sydney, Sydney, New South Wales, Australia.
  9. Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Victoria, Australia.
  10. Monash Infectious Diseases, Monash Health, Clayton, Victoria, Australia.
  11. Centre for Inflammatory Diseases, Monash University, Clayton, Victoria, Australia.
  12. Taylor Square Private Clinic, Darlinghurst, New South Wales, Australia.
  13. Department of Sexual Health Medicine and Sexual Assault Medical Service, Sydney Local Health District, Sydney, New South Wales, Australia.
  14. Discipline of Medicine, Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
  15. Positive Life, Sydney, New South Wales, Australia.
  16. Kirby Institute, University of New South Wales Sydney, Sydney, New South Wales, Australia. kpetoumenos@kirby.unsw.edu.au.
  17. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. sarah-jane.dawson@petermac.org.
  18. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia. sarah-jane.dawson@petermac.org.
  19. Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia. sarah-jane.dawson@petermac.org.
  20. Kirby Institute, University of New South Wales Sydney, Sydney, New South Wales, Australia. mpolizzotto@kirby.unsw.edu.au.
  21. St Vincent's Hospital, Darlinghurst, New South Wales, Australia. mpolizzotto@kirby.unsw.edu.au.
  22. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. mark.dawson@petermac.org.
  23. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia. mark.dawson@petermac.org.
  24. Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia. mark.dawson@petermac.org.

Abstract

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.

Presented By: Nila Dharan and Paul Yeh

Cancer Biology, MedicineNicholas Liao2021-06 (Jun)