Vigano A, Saresella M, Trabattoni D, et al. J Pediatr. 2004;145:542–548
Purpose of the Study.
Growth hormone (GH) plays a role in thymic function, and decreased hormone secretion has been reported in HIV-infected children. Highly active antiretroviral therapy suppresses HIV replication and results in increases in CD4+ T cells in HIV-infected patients. The aim of this study was to determine if the level of immune reconstitution associated with antiretroviral therapy is influenced by the status of the GH insulin-like growth factor 1 axis.
HIV-infected children (n = 26) were studied. Half of them had GH deficiency as defined by a reduced peak GH response to GH-releasing hormone and arginine-stimulation test. These patients were matched to 13 patients of similar age, pubertal status, and clinical findings but with normal GH-response tests.
Thymic volume was measured with magnetic resonance imaging. Peripheral blood lymphocyte subsets were evaluated with standard monoclonal antibody techniques. Serum interleukin 7 levels were measured with an enzyme-linked immunosorbent assay.
The 2 patient populations did not differ in age, weight, height, body mass index, pubertal status, clinical or immunologic stage of disease, or number and percentage of CD4+ T cells before beginning antiretroviral therapy. After antiretroviral therapy, children with GH deficiency had reduced CD4+ T-cell numbers and percentages, reduced interleukin 7 concentrations, and reduced thymic volumes. “Naive” CD4+ T cells were lower in the GH-deficient children, as were central memory T cells. In contrast, effector memory CD4+ T cells and effector CD8+ T cells were increased in the GH-deficient children.
Thymic and postthymic lymphocyte pathways are impaired in HIV-infected children, and antiretroviral therapy–associated immune reconstitution is often incomplete. GH might be useful in the management of HIV-infected children with GH deficiency and incomplete immune reconstitution with antiretroviral therapy.
The reasons why some patients respond to antiretroviral therapy more effectively than others is generally unknown. However, this study suggests that some of this variation may be related to the GH axis of the infected patients. Whether GH-replacement therapy will improve the immune reconstitution in GH-deficient subjects awaits clinical trials. Of interest, also, would be the effect of GH treatment on subjects with incomplete immune reconstitution but normal GH-stimulation studies.