Abstract
Given the melanocortin-4 receptor's (MC4R) importance in obesity, we examined associations between MC4R gene variants and weight following a switch to integrase inhibitor-containing antiretroviral therapy among participants in Advancing Clinical Therapeutics Globally studies. Among 529 persons with HIV (median age: 50 years, 29% non-Hispanic Black, 22% female), 62% were overweight or obese at integrase strand transfer inhibitor switch, and 62% switched to raltegravir. In adjusted linear models, three variants were associated (P < .05) with weight change after switch in all participants or in prespecified subgroups. These exploratory findings are consistent with the role of melanocortins in appetite and weight and suggest a neuroendocrine contribution to integrase inhibitor-related weight gain.