Infect Dis Ther. 2026 Jan 21. doi: 10.1007/s40121-026-01302-x. Online ahead of print.
ABSTRACT
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.
PMID:41563586 | DOI:10.1007/s40121-026-01302-x