Weighing In: Glucagon-Like Peptide-1 Receptor Agonism for Persons With HIV

Weight gain among persons with HIV PWH) on contemporary antiretroviral therapy (ART) can extend beyond an initial return-to-health phenomenon and lead to overweight/obesity in the first 1 to 2 years, resulting in enhanced cardiometabolic risk. Factors that may contribute to increased weight gain include specific ART regimens (those initiating dolutegravir and tenofovir alafenamide or withdrawing tenofovir disoproxil and efavirenz), women with HIV, and certain virologic factors including lower baseline CD4 count and higher HIV viral load. Weight reduction starting at 5% body weight confers metabolic protection, such as improved hypertension and dysglycemia. Even greater metabolic impact has been shown with weight reduction in the approximate range of 15% body weight, as evidenced by decreases in cardiovascular disease mortality. Effective weight management is essential to reducing cardiometabolic risk, may not be achieved with lifestyle changes alone, and requires other therapeutic strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are well recognized to provide potent weight reduction among persons with overweight/obesity; in addition, studies have shown cardiovascular benefit among those with established cardiovascular disease. Recent studies have permitted us to begin to understand the potential role of GLP-1 RAs among PWH and overweight/obesity. This review highlights weight gain specific to PWH and discusses current evidence and key clinical considerations for GLP-1 RA use among PWH.