AIDS. 2026 Mar 31. doi: 10.1097/QAD.0000000000004512. Online ahead of print.
ABSTRACT
BACKGROUND AND OBJECTIVES: Cardiovascular disease (CVD) remains elevated among people with HIV (PWH) despite virological suppression. Whether metabolic-hepatic abnormalities contribute to vascular remodeling during contemporary integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) remains uncertain. We evaluated long-term carotid intima-media thickness (cIMT) trajectories and their metabolic, hepatic, and inflammatory determinants.
METHODS AND DESIGN: We conducted a 5-year prospective cohort study of virologically suppressed adults receiving INSTI-based ART. cIMT was measured at baseline, 48, 96, and 240 weeks. Mixed-effects models assessed longitudinal cIMT, and a complementary increment-based model evaluated predictors of visit-to-visit cIMT change. Measures of insulin resistance (TyG, HOMA-IR), hepatic steatosis (HSI, FLI), and inflammatory biomarkers (D-dimer, sCD14, sCD163, hsCRP, sICAM-1) were evaluated. Mediation through ASCVD risk was explored.
RESULTS: Among 101 participants, cIMT increased significantly over 5 years. In multivariable mixed-effects models, ASCVD risk, HSI, TyG, and D-dimer were independently associated with cIMT. In increment-based analyses (visit-to-visit change in cIMT), hepatic steatosis as assessed by the hepatic steatosis index (HSI) was the only metabolic or inflammatory variable independently associated with short-term cIMT progression (OR 1.042, 95% CI 1.008-1.079). HSI exerted a fully direct effect on cIMT progression (p < 0.001), without mediation through ASCVD risk, and increased the explained variance by 5.1% beyond ASCVD alone. TyG, D-dimer and sCD163 were associated with cIMT in mixed-effects models, but not with cIMT increments.
CONCLUSIONS: HSI-defined hepatic steatosis contributed independently and incrementally to subclinical atherosclerosis progression in PWH receiving INSTI-based ART, beyond traditional cardiovascular risk estimation. Incorporating simple hepatic-metabolic indices such as HSI may improve cardiovascular risk stratification in this population.
PMID:41921079 | DOI:10.1097/QAD.0000000000004512