Our hypothesis was that persistent HIV RNA production in lymphatic tissues—though undetectable in plasma—-leads to chronic inflammation and IA, resulting in abnormalities in the production of the incretin GLP-1 and other protective hormones, which, in turn may predispose to metabolic abnormalities increasingly seen in PWH, including diabetes, steatosis, and obesity. Here, GCG is linked to obesity due to melanocortin 4 receptor deficiency.