Luput-Andrica IM; University of Medicine and Pharmacy
Timisoara, Romania.
Marinescu AR; Cut TG; Herlo A; et al

International Journal of Molecular Sciences. 27(15), 2026 Jul 28.
Headings by Dr Older

Background Despite the success of modern antiretroviral therapy in achieving
virological suppression, people living with HIV face an elevated risk of
cardiovascular diseases, particularly heart failure with preserved
ejection fraction.
Aims This study evaluates the cardiometabolic phenotype and
functional capacity in a Romanian HIV cohort to delineate the metabolic
footprint of chronic infection.
Methods In this cross-sectional study based on
prospectively collected, protocol-driven phenotyping, we evaluated 50
consecutive outpatients from a university-affiliated infectious diseases
clinic in Timisoara. Eligibility strictly required clinical stability and
sustained virological suppression (plasma HIV-RNA < 50 copies/mL for >=12
months).
Results The analysis revealed widespread metabolic dysregulation, with
52% exhibiting excess weight and 64% showing atherogenic dyslipidemia.
Integrase strand transfer inhibitor-based regimens were significantly
correlated with an increased body mass index (p = 0.034) and elevated LDL
cholesterol (aOR = 2.4, 95% CI [1.18-4.95], p = 0.022). Furthermore, we
observed a pronounced metabolic age gap (+4.5 +/- 2.8 years), defined as
the deviation of bioimpedance-estimated metabolic age from the patients’
chronological age. This gap (p = 0.028), alongside historical
immunodeficiency indicated by a low nadir CD4+ count (aOR = 0.998, 95% CI
[0.991-0.999], p = 0.021), strongly predicted exercise intolerance,
independent of current immune reconstruction. Sarcopenic obesity (present
in 18% of the cohort) and an elevated triglycerides-to-HDL ratio (aOR =
2.14, 95% CI [1.15-3.98], p = 0.016) emerged as robust independent
negative predictors of functional capacity. Additionally, subclinical
myocardial remodeling, evidenced by impaired Global Longitudinal Strain,
significantly predicted reduced aerobic capacity (aOR = 0.72, 95% CI
[0.58-0.89], p = 0.003).
Conclusions Consequently, contemporary HIV management must
transition beyond virological control to integrated cardiometabolic
screening. Utilizing cardiopulmonary exercise testing, echocardiography,
and metabolic biomarkers is critical for the early identification of
subclinical “functional HIV-associated frailty” and mitigating the
trajectory toward overt cardiovascular diseases.