Long-term antiretroviral therapy (ART) provides durable viral suppression and extended life expectancy in people living with HIV (PLWH). However, metabolic, cardiovascular, and renal comorbi­dities frequently develop despite virologic control, reflecting the cumulative effects of aging, chronic inflammation, and long-term drug exposure. We report a 25-year clinical course of a man diagnosed with HIV in 1993 who maintained viral suppression and stable CD4 counts for more than two decades. Despite excellent ART adherence and effectiveness, he developed metabolic syndrome and progressive dyslipidaemia, hypertension, carotid arteries stenosis, intermittent claudication, type 2 diabetes, hepatic steatosis, and ultimately end-stage renal disease requiring dialysis. Long-term exposure to several generations of antiretroviral agents, including stavudine, saquinavir, abacavir, and tenofovir disoproxil fumarate, likely contributed to meta­bolic and vascular toxicity. Social circumstances – homelessness, limited access to multidisciplinary care, and low health literacy regarding non-HIV conditions – hindered adequate prevention and treatment of comorbidities. The patient died in 2024 from myocardial infarction and sepsis. This case illustrates that successful viral suppression alone does not prevent metabolic and cardiovascular complications in aging PLWH. Cumulative ART toxicity, lifestyle factors, and social determinants all contributed to an adverse outcome. Comprehensive care should integrate proactive risk- factor management, patient education, and close coordination between HIV and primary care services to improve long-term health and survival in this population.