Noninvasive assessment of coronary artery calcification in people living with human immunodeficiency virus

Coronary artery calcification (CAC) is a well-established marker of subclinical coronary atherosclerosis and a powerful predictor of cardiovascular events. In people living with human immunodeficiency virus (HIV) (PLWH), the progression of CAC is accelerated due to the complex interplay between traditional cardiovascular risk factors and HIV-specific contributors, including chronic inflammation, immune activation, and long-term antiretroviral therapy (ART). This review aims to synthesize current evidence on the epidemiology, pathophysiology, and clinical implications of CAC in PLWH while critically evaluating existing risk stratification approaches and exploring novel integrative strategies for early cardiovascular disease (CVD) screening. We summarize data on the prevalence and prognostic significance of CAC across diverse PLWH populations, noting that CAC scoring provides independent prognostic value over and above traditional risk calculators, which frequently underestimate CVD risk in this population. The underlying mechanisms involve HIV-associated arterial inflammation, altered macrophage activity, and increased vascular-calcification pathways. Noninvasive assessment of CAC using cardiac computed tomography is reliable and reproducible, yet its clinical adoption in HIV care remains limited. We further discuss the association between CAC and long-term mortality, as well as major knowledge deficiencies, including the lack of prospective trials validating CAC-guided preventive strategies in PLWH. Integrating CAC detection with novel biomarkers—such as inflammatory cytokines (e.g., IL-6, hs-CRP), immune activation markers (e.g., CD8 + T-cell subsets, sCD163), and genetic susceptibility captured by polygenic risk scores for coronary artery disease—may significantly improve risk prediction. While polygenic risk scores have shown associations with CAC in PLWH, their performance varies by racial or ethnic group and HIV serostatus. Accordingly, we propose a multimodal risk model that combines CAC scores with inflammatory, immune, and genetic biomarkers to identify individuals at highest risk for rapid CAC progression and future cardiovascular events. The development and prospective validation of such integrated screening pathways are essential for translating these findings into clinical practice, enabling targeted, timely, and personalized preventive interventions in PLWH.