Study of the IGF-IGFBPs in HIV-positive children: correlation with growth

Abstract

HIV infection in children is a health problem, mainly in developing countries. Daily 1500 new children are infected mainly by vertical transmission that is responsible for 85% of the cases. In Brazil there is an increasing population of children infected by HIV early in life. These patients carry the stigma and the complications of HIV infection throughout the growth period of childhood and adolescence. Also, they show deficient weight and height gain, increased frailty, difficulty to couple with stress conditions like infections and consequent high morbidity and mortality rates.Preliminary studies have reported that endocrine disorders like hypothyroidism, diabetes mellitus, adrenal insufficiency or growth hormone (GH) deficiency are uncommon in these patients. However, many of them have reduced levels of insulin-like growth factor I (IGF-I). IGF-I is a peptide hormone that, together with IGF-II, is considered to be the real growth promoter. The IGFs (I and II) are the main integrants of a complex hormonal system that has many interactions and regulation points. Differently from others peptide hormones, the IGFs are bound in the circulation and in the extracellular space to a family of binding proteins (insulin-like growth factor binding proteins: IGFBP-1, -2, -3, -4, -5 and -6), each one with distinct regulation. The IGF system, that also includes an acid-labile subunit (ALS) and 2 specific IGF receptors (IGF1R and IGF2R), is a dynamic system and the concentrations of the different components can change accordingly to many factors such as nutritional status, chronic disease, inflammation, excess or deficiency of other hormones or some medicines. Studies regarding IGF-I in HIV children are scarce, inconclusive and often do not contemplate all components of the IGF system. This information could open new possibilities of clinical intervention in order to minimize the growth arrest observed in this population and thus improve social inclusion. In this research project we propose to study a cohort of HIV-infected children in order to study possible correlations between linear growth and the concentrations of the different components of the IGF system and of inflammatory cytokines, as well as the control of HIV infection. AIMS: To study the concentrations of different components of the IGF system (IGF-I, IGF-II, IGFBPs, IGFBP-3 protease activity, ALS) in HIV children, and to analyze possible correlations between growth rate, HIV infection control status and serum concentration of inflammatory cytokines and C-reactive protein (CRP). METHODS: We will conduct a prospective study of a cohort of HIV-infected children. Patients (prepubertal children vertically infected with HIV, aged 5 to 12 years) will be clinically evaluated over a period of 1 year. At time zero (inclusion in the study) and at 6 and 12 months they will have their weights and heights evaluated by the same examiner and have a sample of their blood taken for measurement of the components of the IGF system (IGF-I, IGF-II, IGFBPs, IGFBP-3 protease activity, ALS), inflammatory cytokines (IL-2, IL-6, TNF-alpha), and CRP and for general tests essential for the assessment of the control of HIV infection. IGF-I, IGF-II, IGFBP-3, cytokines and CRP will be measured by immunoassays, while others IGFBPs and ALS will be analyzed by Western ligand- and immuno-blotting. A control group will be composed of healthy prepubertal age-matched children who will undergo blood sampling for elective presurgical procedures. They will have their weights and heights evaluated by the same examiner and have a sample of their blood taken for measurement of the components of the IGF system, inflammatory cytokines and CRP. Statistical analyses include description of continuous variables, constructions of 95% confidence intervals, test of hypothesis for mean difference and linear regression for correlations. (AU)