Use of human recombinant growth hormone and human recombinant insulin-like growth factor-I in patients with human immunodeficiency virus infection.

Abstract

Infection with the human immunodeficiency virus (HIV) can lead to global alterations in metabolism as well as immunodeficiency. There is dysregulation of endocrine function in adults and children, the extent and magnitude correlating with disease progression. Some of the more prominent abnormalities occur in the thyroid, gonadal, and somatomedin axes. Clinical manifestations of these abnormalities are growth failure in children, which is one of the most sensitive indicators of disease progression, and a wasting syndrome in adults and children. Although there are case reports of growth hormone (GH) deficiency in HIV-infected children, most patients with growth failure have normal serum levels of GH and normal to low levels of insulin-like growth factor-I (IGF-I). Antiretrovial therapy can improve the growth rate in children for a period of time if there is a drop in viral titer, but as the viral load increases, the growth rate decreases again. Administration of GH or IGF-I to these patients can improve the growth rate and lean body mass, and in some patients improve immune function. Although studies on resting energy expenditure in HIV-infected patients have shown increases, these are not proportional to disease progression, but may be dependent upon cytokine activation and other abnormalities. Adult patients with wasting have been shown to have relatively normal total energy expenditure, but decreased intake. Appetite stimulants have been shown to have some benefit, but do not increase lean body mass. The most significant clinical benefit has come from administration of GH in short-term trials. GH and IGF-I are both able to inhibit apoptosis and reconstitute the immune system in rodents treated with ablative therapy. In addition, GH can modulate the marrow suppressive effects of zidovudine and may enhance its ability to inhibit viral reverse transcriptase. Current clinical trials are ongoing in both adults and children. GH and IGF-I may have a role in regimens intended for immune reconstruction, and could be useful as adjuvant therapy in selected patients with HIV infection.