Growth hormone in HIV/AIDS: current uses and future prospects

Recombinant human growth hormone (rhGH) and its primary induced product, insulin-like growth factor-I (IGF-I), have beneficial effects on a myriad of syndromes associated with catabolic metabolism in children and in adults. Their ability to promote nitrogen retention and protein synthesis and to enhance lipolysis has translated into significant increases in body weight, lean body mass, and sense of well-being among HIV+ individuals with wasting syndromes. These changes, first observed in limited phase I studies, have now been confirmed by two large, controlled clinical trials. The alterations are consistent with the low GH and/or IGF-I levels observed in HIV infection, as well as the relative resistance to GH. Whether long-term outcome in HIV disease is altered by such therapies remains to be determined, however. The ability of GH to augment cellular immune function and modulate T lymphocyte trafficking in animal models of immune suppression has also led to examination of its impact on CD4+ T cell counts and viral load in HIV infection. There is currently little evidence that short-term rhGH administration has any lasting impact on T cell biology in the setting of HIV disease. However, preliminary reports that, in vitro, GH alters immune cell apoptosis and enhances the efficacy of Zidovidine (AZT), similar to changes observed with granulocyte-macrophage colony-stimulating factor, may lead to additional uses for GH. Studies to define the mechanism of action of GH and IGF-I on normal and abnormal immune homeostasis in children and adults should enhance our ability to design effective treatments for those with acquired immune deficiency syndrome (AIDS) and perhaps other wasting and immune suppressive disorders.