A Narrative Review of Metabolic Syndrome in People Living With HIV: Insights From the Cardiovascular-Kidney-Metabolic Framework

The widespread use of antiretroviral therapy has substantially improved survival among people living with HIV (PLWH), shifting HIV care from opportunistic infection control toward the prevention of long-term non-communicable comorbidities. Metabolic syndrome (MetS) is a common and clinically useful marker of clustered metabolic abnormalities in this population. In PLWH, MetS may arise from the combined effects of HIV-related chronic inflammation, ART-associated metabolic changes, and altered adipose tissue distribution, including peripheral lipoatrophy, central obesity, and visceral fat accumulation. However, conventional MetS definitions mainly identify metabolic abnormalities and do not capture their severity, target-organ involvement, or broader kidney and cardiovascular implications. The cardiovascular-kidney-metabolic framework proposed by the American Heart Association links metabolic risk, kidney dysfunction, and cardiovascular disease across progressive stages. In this Review, we summarize the diagnostic criteria, epidemiology, and major determinants of MetS in PLWH and reinterpret this evidence within the cardiovascular-kidney-metabolic framework. We discuss how antiretroviral therapy exposure, immune activation and inflammation, virological control, aging, adiposity, and lifestyle factors may shape cardiovascular-kidney-metabolic risk. Applying this framework to chronic HIV care may move practice beyond MetS identification toward longitudinal assessment of metabolic status, kidney involvement, and cardiovascular risk. This approach may support earlier risk detection, individualized monitoring, antiretroviral regimen optimization, lifestyle intervention, and multidisciplinary prevention.