RESEARCH PAPER
Impact of clinical status at the time of HIV diagnosis on intensity of epigenetic ageing in HIV-infected men treated with integrase inhibitors
More details
Hide details
1
Department of Infectious Diseases, Liver Disease and Acquired Immune Deficiencies, Wroclaw Medical University, Poland
2
Department of Forensic Medicine, Division of Molecular Techniques, Wroclaw Medical University, Poland
3
Department of Control Systems and Mechatronics, Faculty of Information and Communication Technology, Wroclaw University of Science and Technology, Poland
4
1st Infectious Diseases Ward, J. Gromkowski Provincial Specialist Hospital in Wroclaw, Poland
Submission date: 2026-03-30
Acceptance date: 2026-05-05
Publication date: 2026-06-10
KEYWORDS
TOPICS
ABSTRACT
Background:
We have recently published a study indicating that, given a wide range of confounding factors, human immunodeficiency virus (HIV) infection remains an independent factor accelerating epigenetic ageing. In this research, a detailed analysis of medical history of ten (n = 10) participants from our previous study was conducted, for whom extreme results of global DNA methylation, a key marker of epigenetic ageing, were obtained.
Material and methods:
The current study included five (n = 5) patients with the highest levels of global DNA methylation, and five (n = 5) with the lowest levels of global DNA methylation. The current analysis focused particularly on clinical status at the time of HIV diagnosis and at the start of combined antiretroviral therapy.
Results:
In the analysis of continuous variables, no significant differences between groups were reported, even without multi-test corrections. This was attributable to small group sizes. The strongest (most negative) association was observed between global DNA methylation and years since HIV diagnosis (ρ = –0.400, permutation p = 0.249), followed by HIV RNA at diagnosis (ρ = –0.309, p = 0.386).
Conclusions:
No common, distinct feature distinguishing HIV-infected individuals with low versus high global DNA methylation levels was identified. However, the results suggest a negative correlation between the global DNA methylation level and the time since HIV diagnosis as well as viral load at diagnosis.
REFERENCES (22)
1.
Gueler A, Moser A, Calmy A, Günthard HF, Bernasconi E, Furrer H, et al. Life expectancy in HIV-positive persons in Switzerland: matched comparison with general population. AIDS 2017; 31: 427-436.
2.
Wandeler G, Johnson LF, Egger M. Trends in life expectancy of HIV-positive adults on antiretroviral therapy across the globe: comparisons with general population. Curr Opin HIV AIDS 2016; 11: 492-500.
3.
Marcus JL, Leyden WA, Alexeeff SE, Anderson AN, Hechter RC, Hu H, et al. Comparison of overall and comorbidity-free life expectancy between insured adults with and without HIV infection, 2000-2016. JAMA Network Open 2020; 3: e207954. DOI: 10.1001/jamanetworkopen.2020.7954.
4.
Rodes B, Cadinanos J, Esteban-Cantos A, Rodríguez-Centeno J, Arribas JR. Ageing with HIV: challenges and biomarkers. EBioMedicine 2022; 77: 103896. DOI: 10.1016/j.ebiom.2022.103896.
5.
Field AE, Robertson NA, Wang T, Havas A, Ideker T, Adams PD. DNA methylation clocks in aging: categories, causes, and consequences. Mol Cell 2018; 71: 882-895.
6.
Unnikrishnan A, Hadad N, Masser DR, Jackson J, Freeman WM, Richardson A. Revisiting the genomic hypomethylation hypothesis of aging. Ann N Y Acad Sci 2018; 1418: 69-79.
7.
Duan R, Fu Q, Sun Y, Li Q. Epigenetic clock: a promising biomarker and practical tool in aging. Ageing Res Rev 2022; 81: 101743. DOI: 10.1016/j.arr.2022.101743.
8.
Bożejko M, Knysz B, Czernicka A, Tarski I, Szymczak A, Małodobra-Mazur M. HIV infection is associated with accelerated epigenetic ageing: a systematic review. Ageing Res Rev 2025; 112: 102884. DOI: 10.1016/j.arr.2025.102884.
9.
Bożejko M, Małodobra-Mazur M, Gnatowski A, Ołdakowska M, Szymczak A, Szetela B, et al. HIV infection as an independent factor accelerating epigenetic ageing in men treated with integrase inhibitors: a case-control study. Viruses 2026; 18: 199. DOI: 10.3390/v18020199.
10.
Zhang J, Sehl ME, Shih R, Breen EC, Li F, Lu AT, et al. Effects of highly active antiretroviral therapy initiation on epigenomic DNA methylation in persons living with HIV. Front Bioinform 2024; 4: 1357889. DOI: 10.3389/fbinf.2024.1357889.
11.
Abdeljelil M, Kooli I, Bouchahda N, Achour A, Harzallah G, Golli M, et al. Sub-clinical atherosclerosis in HIV-infected patients: prevalence and risk factors. HIV AIDS Rev 2023; 22: 290-294.
12.
Kumar S, Pandey VP, Thakur A. The effect of antiretroviral therapy in newly diagnosed people living with HIV and AIDS, and their correlation with common inflammatory markers and lipid profile. HIV AIDS Rev 2024; 23: 130-135.
13.
Macedo LFR, dos Santos Cardoso G, dos Santos NAT, de Sousa Menezes RT. Body weight gain in HIV-positive people treated with antiretroviral therapy in Brazil. HIV AIDS Rev 2024; 23: 107-108.
14.
Sehgal R, Borrus D, Kasamato J, Armstrong JF, Gonzalez J, Markov Y, et al. DNAm aging biomarkers are responsive: Insights from 51 longevity interventional studies in humans. bioRxiv [Preprint]. 2024 Oct 25. DOI: 10.1101/2024.10.22.619522.
15.
Simpson DJ, Chandra T. Epigenetic age prediction. Aging Cell 2021; 20: e13452. DOI: 10.1111/acel.13452.
16.
Oblak L, van der Zaag J, Higgins-Chen AT, Levine ME, Boks MP. A systematic review of biological, social and environmental factors associated with epigenetic clock acceleration. Ageing Res Rev 2021; 69: 101348. DOI: 10.1016/j.arr.2021.101348.
17.
Lundgren S, Kuitunen S, Pietiläinen KH, Hurme M, Kähönen M, Männistö S, et al. BMI is positively associated with accelerated epigenetic aging in twin pairs discordant for body mass index. J Intern Med 2022; 292: 627-640.
18.
Robinson O, Chadeau Hyam M, Karaman I, Climaco Pinto R, Ala-Korpela M, Handakas E, et al. Determinants of accelerated metabolomic and epigenetic aging in a UK cohort. Aging Cell 2020; 19: e13149. DOI: 10.1111/acel.13149.
19.
Liang X, Justice AC, Marconi VC, Aouizerat BE, Xu K. Co-occurrence of injection drug use and hepatitis C increases epigenetic age acceleration that contributes to all-cause mortality among people living with HIV. Epigenetics 2023; 18: 2212235. DOI: 10.1080/15592294.2023.2212235.
20.
Heany SJ, Levine AJ, Lesosky M, Phillips N, Fouche JP, Myer L, et al. Persistent accelerated epigenetic ageing in a longitudinal cohort of vertically infected HIV-positive adolescents. J Neurovirol 2023; 29: 3. DOI: 10.1007/s13365-023-01130-6.
21.
Dye CK, Wu H, Jackson GL, Kidane A, Nkambule R, Lukhele NG, et al. Epigenetic aging in older people living with HIV in Eswatini: a pilot study of HIV and lifestyle factors and epigenetic aging. Clin Epigenet 2024; 16: 1. DOI: 10.1186/s13148-024-01629-7.
22.
Esteban-Cantos A, Montejano R, Rodríguez-Centeno J, Saiz-Medrano G, De Miguel R, Barruz P, et al. Longitudinal changes in epigenetic age acceleration in aviremic human immunodeficiency virus-infected recipients of long-term antiretroviral treatment. J Infect Dis 2022; 225: 2. DOI: 10.1093/infdis/jiab338.