PROTEOLYSIS OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-3 IN HUMAN IMMUNODEFICIENCY VIRUS-POSITIVE CHILDREN WHO FAIL TO THRIVE

Failure to thrive is a common manifestation of human immunodeficiency virus (HIV) infection in children. Given the role of insulin-like grow th factor I (IGF-I) in stimulating postnatal growth, we have examined whether HIV-infected pediatric patients with growth failure have lower serum concentrations of IGF-I than age-matched control subjects. IGF- I was measured in 16 HIV-infected children and 13 HIV-negative control s. Ten of the HIV-infected children failed to thrive based on height a nd linear growth that was below the National Center for Health Statist ics 10th percentile. IGF-I levels were significantly lower in children who failed to thrive compared to those in age-matched controls (20 vs . 60 mu g/L; P < 0.001). Children who failed to thrive also displayed lower IGF-I levels than HIV-positive children, who exhibited normal gr owth velocity (20 vs. 91 mu g/L; P < 0.001). Failure to thrive was ass ociated with a significant reduction in circulating levels of IGF-bind ing protein-3 (IGFBP-3), as determined by Ligand and Western blotting (P < 0.001), enhanced IGFBP-3 proteolysis (P < 0.001), and a decrease in the serum concentration of the acid-labile subunit of the IGFBP-3 t ernary complex (P < 0.005). IGFBP-3 proteolysis was negatively correla ted with IGF-I (r = 0.78) and IGFBP-3 levels (r = 0.70). Failure to th rive was associated with a reduction in the formation of the ternary c omplex, but the ternary complex could be restored by the addition of a n excess of IGFBP-3 to serum. These results indicate that low levels o f IGF-I, IGFBP-3, and acid-labile subunit are associated with a failur e to thrive in HIV-infected children.