Poster Presentation 38th Lorne Cancer Conference 2026

Divergent patterns for genetic alterations drive pre-malignant clonal haematopoiesis in people with HIV (#115)

Kiarash Behrouzfar 1 , Win M Han 2 , Rashindrie Perrera 3 4 , Jason Li 4 , Katherine E Scull 1 , Kerryn Howlett 1 , Mark Bloch 2 5 , David A Baker 6 , Beng Eu 7 8 , Ellen Bowden-Reid 2 , Don Smith 9 10 , Jennifer F Hoy 11 , Ian Woolley 1 11 12 , Robert Finlayson 13 , David J Templeton 2 14 15 , Gail V Matthews 2 16 , Jane Costello 17 , Mark A Dawson 18 19 20 , Sarah-Jane Dawson 18 19 20 , Mark N Polizzotto 2 21 , Kathy Petoumenos 2 , Nila J Dharan 2 , Paul Yeh 1 22
  1. Medicine, Monash University, Clayton, Melbourne, Victora, Australia
  2. Kirby Institute, University of New South Wales, Sydney, NSW, Australia
  3. School of Electrical, Mechanical and Infrastructure Engineering, University of Melbourne, Melbourne, Victoria, Australia
  4. Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  5. Holdsworth House Medical Practice, Sydney, NSW, Australia
  6. East Sydney Doctors, Sydney, NSW, Australia
  7. Prahran Market Clinic, Melbourne, VIC, Australia
  8. Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia
  9. Albion Centre, South Eastern Sydney Local Health District, Sydney, NSW, Australia
  10. School of Population Health, University of New South Wales, Sydney, NSW, Australia
  11. Department of Infectious Diseases, School of Translational Medicine, The Alfred Hospital and Monash University, Melbourne, VIC, Australia
  12. Centre for Inflammatory Diseases, Monash University, Melbourne, VIC, Australia
  13. Taylor Square Private Clinic, Darlinghurst, NSW, Australia
  14. Department of Sexual Health Medicine , Sydney Local Health District, Sydney, NSW, Australia
  15. Discipline of Medicine, Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
  16. St Vincent’s Hospital, Darlinghurst, NSW, Australia
  17. Positive Life, Sydney, NSW, Australia
  18. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  19. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia
  20. Collaborative Centre for Genomic Cancer Medicine, University of Melbourne, Melbourne, VIC
  21. Clinical Hub for Interventional Research, Australian National University, Canberra, ACT, Australia
  22. Monash Haematology, Monash Health, Clayton, Melbourne, VIC, Australia

Background

Clonal haematopoiesis (CH) is characterised by the clonal expansion of haematopoietic stem cells driven by genetic alterations including somatic gene mutations (SGMs) and mosaic chromosomal alterations (mCAs) that are potentially associated with increased comorbidity risk. Given the increased risk of cancers associated with CH in people with HIV (PWH), evaluating the relationship of SGMs and mCA with HIV is critical to understanding the biological and clinical significance of different origins of CH in PWH. We previously showed that SGMs are more prevalent in older PWH and are associated with higher levels of chronic inflammation markers that can potentially contribute to pre-malignant milieu, associated with increased risk of cancers in PWH. However, whether mCAs also show similar patterns to SGMs remains unknown.

Method

We processed whole blood samples of 445 participants aged 55 years or older, including 219 PWH and 226 participants without HIV for SNP array genotyping and utilised MOsaic CHromosomal Alterations (MoChA) software to detect mCA from the genotype data.

Results

Of 445 participants, the majority were male (96.2%), with a median age of 63 (interquartile range (IQR)=59-69) years. While mCA events were detected in 13.5% of participants, we found for the first time, a markedly lower mCA prevalence in PWH compared to participants without HIV (8.7% vs 18.1%, p=0.003). This was consistent by inverse association observed between the presence of mCA and HIV infection after adjusting for age, sex, smoking history and SGM status. Although SGMs and mCAs co-occurred infrequently (13.1%), no statistically significant evidence of mutual exclusivity was observed. Among PWH, blood cell counts and levels of inflammatory markers were not associated with mCA, but lower current CD4+ T cell count (0.88 adjusted odds ratio, 95% CI: 0.79, 0.98) was associated with the presence of mCA.

Conclusion

Given the divergent patterns of mCA and SGMs prevalence in our cohort, their infrequent co-occurrence and their distinct associations with chronic inflammation markers and CD4+ T cell counts in PWH, our findings suggest different selective pressures that may drive pre-malignant CH, with potentially distinct implications for comorbidity risk.