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Background <p>Telomere length (TL) is a widely used biomarker of biological aging, and is shortened in people living with HIV (PWH) due to chronic inflammation and immune-activation. The DNA methylation-based estimator of TL (DNAmTL) has emerged as a promising alternative to classical TL measurements, but their comparative performance in PWH remains poorly characterized.</p> Methods <p>We conducted a cross-sectional study comparing DNAmTL and monochrome multiplex quantitative PCR-based TL (qPCR-TL) in two cohorts of PWH: 160 ART-naïve individuals and 143 long-term treated individuals with sustained viral suppression. DNAmTL was derived from blood DNA methylation profiles generated using the Infinium MethylationEPIC arrays, while qPCR-TL was measured using a standardized assay. We evaluated the agreement between methods using correlation, Bland-Altman analysis and Cohen’s Kappa coefficient, and their associations with demographic, clinical and immunological factors were assessed using multivariable linear regression.</p> Results <p>DNAmTL and qPCR-TL were moderately correlated in both ART-naïve (<i>r</i> = 0.54, <i>p</i> &lt; 0.001) and ART-treated participants (<i>r</i> = 0.46, <i>p</i> &lt; 0.001), showing reasonable to fair agreement across continuous and categorical assessments. Both measures were inversely correlated with chronological age, although associations were stronger for DNAmTL. Compared to qPCR-TL, DNAmTL demonstrated more robust and independent associations with female sex and ethnicity, immunovirological markers of HIV disease severity such as plasma HIV-RNA viral load and the CD4:CD8 ratio, as well as with comorbidities including type 2 diabetes and hepatitis C virus coinfection.</p> Conclusions <p>DNAmTL provides a more biologically informative measure of aging and disease burden in PWH. Further research is warranted to validate these results and to determine its predictive value for clinical outcomes.</p>

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DNA methylation-based estimator of blood telomere length (DNAmTL) outperforms qPCR-based telomere length in reflecting clinical and sociodemographic factors in people with HIV infection

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月19日

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  • Andrés Esteban-Cantos,
  • Javier Rodríguez-Centeno,
  • Rocío Montejano,
  • Julen Cadiñanos,
  • Rosa de Miguel-Buckley,
  • Lucía Gutiérrez-García,
  • Cristina Marcelo-Calvo,
  • Patricia Martínez-Martín,
  • Jose I. Bernardino,
  • Alejandro de Gea-Grela,
  • Alejandro Díez-Vidal,
  • Carlos Oñoro,
  • Berta Rodés,
  • José R. Arribas

摘要

Background

Telomere length (TL) is a widely used biomarker of biological aging, and is shortened in people living with HIV (PWH) due to chronic inflammation and immune-activation. The DNA methylation-based estimator of TL (DNAmTL) has emerged as a promising alternative to classical TL measurements, but their comparative performance in PWH remains poorly characterized.

Methods

We conducted a cross-sectional study comparing DNAmTL and monochrome multiplex quantitative PCR-based TL (qPCR-TL) in two cohorts of PWH: 160 ART-naïve individuals and 143 long-term treated individuals with sustained viral suppression. DNAmTL was derived from blood DNA methylation profiles generated using the Infinium MethylationEPIC arrays, while qPCR-TL was measured using a standardized assay. We evaluated the agreement between methods using correlation, Bland-Altman analysis and Cohen’s Kappa coefficient, and their associations with demographic, clinical and immunological factors were assessed using multivariable linear regression.

Results

DNAmTL and qPCR-TL were moderately correlated in both ART-naïve (r = 0.54, p < 0.001) and ART-treated participants (r = 0.46, p < 0.001), showing reasonable to fair agreement across continuous and categorical assessments. Both measures were inversely correlated with chronological age, although associations were stronger for DNAmTL. Compared to qPCR-TL, DNAmTL demonstrated more robust and independent associations with female sex and ethnicity, immunovirological markers of HIV disease severity such as plasma HIV-RNA viral load and the CD4:CD8 ratio, as well as with comorbidities including type 2 diabetes and hepatitis C virus coinfection.

Conclusions

DNAmTL provides a more biologically informative measure of aging and disease burden in PWH. Further research is warranted to validate these results and to determine its predictive value for clinical outcomes.