Weight gain and obesity management in people with HIV: pathophysiology, antiretroviral therapy effects, and clinical strategies.

Obesity is a chronic, relapsing disease that is defended by complex biologic regulatory mechanisms, and is defined by excessive or abnormal adipose tissue that impairs health. Among people with HIV (PWH), the epidemiology of body weight has shifted dramatically in the modern antiretroviral therapy (ART) era, with obesity now replacing wasting and lipodystrophy as dominant body-composition phenotypes. Excess adiposity in PWH arises from overlapping influences: persistent immune activation, ART-specific effects on adipose tissue, and the same environmental factors driving the global obesity epidemic. The consequences include insulin resistance, dyslipidemia, cardiovascular disease, and fatty liver disease, which now constitute the leading causes of morbidity and mortality in this population. This review summarizes the pathophysiology, epidemiology, and management of obesity in PWH, emphasizing mechanisms that link ART exposure to altered adipose biology and metabolic risk. Effective care requires an integrated approach combining behavioral, pharmacologic, and procedural strategies within multidisciplinary HIV programs. Recognizing obesity as a chronic, treatable disease reframes management away from lifestyle blame toward durable metabolic control. In contemporary HIV care, the goal extends beyond viral suppression to encompass the prevention of cardiometabolic disease and preservation of long-term health.