Risk Factors for Major Adverse Cardiovascular Events in Antiretroviral Therapy-Treated People with HIV: A Long-Term Cohort Study in Turkey

People living with HIV (PLWH) continue to experience longer life expectancy due to effective antiretroviral therapy (ART). However, cardiovascular disease (CVD) has become a leading cause of morbidity and mortality. Despite improved HIV care, major adverse cardiovascular events (MACE) remain prevalent, with limited data from long-term cohorts. This study aimed to determine the incidence, risk factors, and predictors of MACE in long-term ACTHIV-IST cohort of PLWH in Istanbul. We conducted a retrospective analysis of 1059 patients followed for at least 10 years. Patients with prior MACE or noncardiac mortality were excluded. Traditional CVD risk factors, HIV-related immunovirological parameters, ART, and comorbidities were analyzed using Cox proportional hazards regression. MACE incidence was 7.55% (80/1059) with a cumulative rate of 11.1%. The most frequent events were ischemic heart disease (30.4%), myocardial infarction (27.6%), and sudden cardiac death (18.6%). Among those without traditional CVD risk factors, a CD4⁺ count <200 cells/mm³ at diagnosis was associated with a 4.5-fold increased MACE risk. Hypertension (hazard ratio [HR]: 4.74), coronary artery disease (CAD) (HR: 8.49), and older age at HIV diagnosis (HR: 1.031/year) were the strongest independent predictors (<i>p</i> < 0.05). Patients who should have used statins but did not were at higher risk of developing MACE (34% vs. 17%) compared to those who did (<i>p</i> < 0.05). Twenty-one statin users of those who had MACE were before the event. A significantly higher MACE rate was observed in patients who used protease inhibitor (PI) compared to those who did not (<i>p</i> = 0.002). Low baseline CD4⁺ T-cell count, prolonged HIV duration, comorbidities (e.g., hypertension, CAD, and dyslipidemia), PI experienced, and older age at HIV diagnosis significantly increase MACE risk. Early diagnosis, continuous cardiovascular monitoring, start statins if indicated, and individualized ART strategies are essential to reduce MACE-related morbidity and mortality in PLWH.