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Introduction <p>Aging in people with HIV (PWH) is accompanied by an increased burden of multimorbidity and persistent inflammation. Identifying biomarkers that reflect comorbidity risk can help improve long-term care. This study evaluated the association of multimorbidity with GDF-15, sICAM-1, sVCAM-1, and sP-selectin in PWH.</p> Methods <p>A cross-sectional study was performed in two cohorts of adults receiving antiretroviral therapy: a discovery cohort (<i>n</i> = 74) and a validation cohort (Spanish CoRIS network) (<i>n</i> = 150). Median age was 53&#xa0;years in both cohorts (IQR 44–60 and 45–58), and women represented 19 (25.7%) and 75 (50.0%), respectively. Multimorbidity was defined as ≥ 2 comorbidities, including but not limited to cardiovascular, metabolic, renal, and non-AIDS-defining cancers. Plasma GDF-15, sICAM-1, sVCAM-1, and sP-selectin were quantified by multiplex immunoassay. Associations with log-transformed GDF-15 were assessed using multivariable linear regression including age-multimorbidity ordinal categories, tobacco smoking, and CD4+ nadir.</p> Results <p>Multimorbidity prevalence was 48.6% (36) in the hospital cohort and 54.7% (82) in CoRIS. In both cohorts, participants with multimorbidity had significantly higher GDF-15 levels (hospital: 771.5 vs. 390.0&#xa0;pg/ml; CoRIS: 485.2 vs. 360.1&#xa0;pg/ml; both <i>p</i> &lt; 0.001). In the hospital cohort, smoking and age-multimorbidity were independently associated with elevated GDF-15, with 26.1% and 16.0% increases per category, respectively (<i>p</i> &lt; 0.05). These associations were confirmed in CoRIS, with 5.44% and 19.0% increases (<i>p</i> &lt; 0.01). CD4+ nadir showed no significant association with GDF-15. No significant associations were observed between multimorbidity and sICAM-1, sVCAM-1, or sP-selectin (all <i>p</i> &gt; 0.05).</p> Conclusions <p>Elevated GDF-15 was consistently associated with multimorbidity in PWH, primarily driven by aging and tobacco smoking. GDF-15 appears to reflect a broader state of multisystem physiological stress than traditional endothelial activation markers, supporting its utility as a biomarker to identify PWH at higher risk of age-related comorbidities and to monitor the impact of modifiable risk factors in clinical care.</p>

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Elevated Plasma GDF-15 Levels Are Associated with Aging, Multimorbidity, and Tobacco Exposure in People with HIV

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月21日

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  • Aida López López,
  • Jacobo Alonso Domínguez,
  • Inés Martínez Barros,
  • Alexandre Pérez González,
  • Antonio Ocampo,
  • Luis Morano,
  • Beatriz Calderón Cruz,
  • Noemí Martínez López de Castro,
  • Otilia Bisbal Pardo,
  • Mayte Pérez-Olmeda,
  • Jorge Sánchez-Villegas,
  • Víctor Asensi,
  • Marta Montero-Alonso,
  • Rafael Rodríguez-Rosado Martínez-Echevarría,
  • Eva Poveda

摘要

Introduction

Aging in people with HIV (PWH) is accompanied by an increased burden of multimorbidity and persistent inflammation. Identifying biomarkers that reflect comorbidity risk can help improve long-term care. This study evaluated the association of multimorbidity with GDF-15, sICAM-1, sVCAM-1, and sP-selectin in PWH.

Methods

A cross-sectional study was performed in two cohorts of adults receiving antiretroviral therapy: a discovery cohort (n = 74) and a validation cohort (Spanish CoRIS network) (n = 150). Median age was 53 years in both cohorts (IQR 44–60 and 45–58), and women represented 19 (25.7%) and 75 (50.0%), respectively. Multimorbidity was defined as ≥ 2 comorbidities, including but not limited to cardiovascular, metabolic, renal, and non-AIDS-defining cancers. Plasma GDF-15, sICAM-1, sVCAM-1, and sP-selectin were quantified by multiplex immunoassay. Associations with log-transformed GDF-15 were assessed using multivariable linear regression including age-multimorbidity ordinal categories, tobacco smoking, and CD4+ nadir.

Results

Multimorbidity prevalence was 48.6% (36) in the hospital cohort and 54.7% (82) in CoRIS. In both cohorts, participants with multimorbidity had significantly higher GDF-15 levels (hospital: 771.5 vs. 390.0 pg/ml; CoRIS: 485.2 vs. 360.1 pg/ml; both p < 0.001). In the hospital cohort, smoking and age-multimorbidity were independently associated with elevated GDF-15, with 26.1% and 16.0% increases per category, respectively (p < 0.05). These associations were confirmed in CoRIS, with 5.44% and 19.0% increases (p < 0.01). CD4+ nadir showed no significant association with GDF-15. No significant associations were observed between multimorbidity and sICAM-1, sVCAM-1, or sP-selectin (all p > 0.05).

Conclusions

Elevated GDF-15 was consistently associated with multimorbidity in PWH, primarily driven by aging and tobacco smoking. GDF-15 appears to reflect a broader state of multisystem physiological stress than traditional endothelial activation markers, supporting its utility as a biomarker to identify PWH at higher risk of age-related comorbidities and to monitor the impact of modifiable risk factors in clinical care.