Impact of HIV on the Hypothalamic-Pituitary Hormonal Axis

The human immunodeficiency virus (HIV) and antiretroviral therapy (ART) have well-established effects on the pituitary-growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis. GH dysregulation likely contributes to the complex defects in energy and lipid metabolism characteristic of persons living with HIV (PLWH). The etiology of GH axis abnormalities is likely multifactorial. Several studies have demonstrated decreased pulse amplitude of GH secretion, associated with increased visceral fat characteristic of HIV-associated dyslipidemic lipodystrophy (HADL). Increased somatostatin tone, decreased ghrelin levels, and direct suppression of GH by elevated free fatty acids have been proposed as mechanisms of the GH secretory defect in patients with HIV. The diagnosis of GH deficiency in patients is challenging due to difficulties in interpreting diagnostic tests in the context of HIV infection and obesity. Several therapies have been proposed for GH deficiency coupled with metabolic disturbances in HIV-infected patients. Tesamorelin, a growth hormone-releasing hormone analog, has been approved for use in the USA. Other therapies, including recombinant human growth hormone (r-hGH) and IGF-1 with insulin-like growth factor-binding protein 3 (IGFBP3), have also been proposed. More detailed understanding of the pathophysiology and treatment of defective GH regulation is needed for innovative and practical treatment of the metabolic defects in PLWH.