INTRODUCTION: Growth failure is a common presenting sign in children with HIV disease and is a sensitive indicator of disease progression in children with AIDS. Highly active antiretroviral therapy (HAART) is associated with a significant decrease in viral load and a subsequent rise in CD4+ T cell counts in HIV-1-infected children and also with increased height and weight. The underlying mechanisms of catch-up growth during HAART are yet unknown. METHODS: Height and weight measurements, blood sample analyses for HIV-1 RNA and peripheral blood CD4+ T cell counts were obtained twice within 1 month before the start of HAART and after 12, 24, 36 and 48 weeks of treatment. Serum concentrations of insulin-like growth factor I (IGF-1), IGFs complexed to specific, structurally homologous binding proteins (IGFBP-3), cortisol, free thyroxine and tumor necrosis factor alpha (TNF-alpha) were measured before the start of therapy and after 24 weeks. In addition serum IGF-1 and IGFBP-3 values were determined after 48 weeks. RESULTS: Twenty-seven HIV-1-infected children with a median age of 5.5 years (range, 0.3 to 14.9 years) were included. Overall no significant changes in height and body mass index (BMI) z scores were observed. The median baseline plasma viral load of 68,800 copies/ml decreased to less than the detection limit of 500 copies/ml in 80% of the children after 48 weeks. TNF-alpha values were elevated (44 pg/ml) at baseline and decreased significantly to 37 pg/ml after 24 weeks. At baseline elevated TNF-alpha was observed in 78%, which decreased to 55% after 24 weeks. Baseline free thyroxine and cortisol values were normal and did not change during therapy. Baseline serum of IGF-1 and IGFBP-3 concentrations were normal, but IGF-1 tended to be lower than IGFBP-3. Both values increased significantly after the initiation of therapy. IGFBP-3 decreased after 48 weeks whereas IGF-1 stabilized. The increase in IGF-1 was significantly higher in children in whom the BMI and length (after correction for age and sex) increased the most. CONCLUSION: Hypothyroidism and adrenal axis abnormalities are not associated with restoration of growth after the initiation of antiretroviral therapy in HIV-1-infected children. The combination of relatively high serum IGFBP-3 concentration and relatively lower serum IGF-1 suggests the presence of a growth hormone-resistant state. During treatment with a protease inhibitor-containing regimen, decreased serum IGFBP-3 and stabilization of IGF-1 after a significant initial increase suggest restoration of normal sensitivity to growth hormone and recovery to an anabolic condition.
INTRODUCTION:Growth failure is a common presenting sign in children with HIV disease and is a sensitive indicator of disease progression in children with AIDS. Highly active antiretroviral therapy (HAART) is associated with a significant decrease in viral load and a subsequent rise in CD4+ T cell counts in HIV-1-infectedchildren and also with increased height and weight. The underlying mechanisms of catch-up growth during HAART are yet unknown. METHODS: Height and weight measurements, blood sample analyses for HIV-1 RNA and peripheral blood CD4+ T cell counts were obtained twice within 1 month before the start of HAART and after 12, 24, 36 and 48 weeks of treatment. Serum concentrations of insulin-like growth factor I (IGF-1), IGFs complexed to specific, structurally homologous binding proteins (IGFBP-3), cortisol, free thyroxine and tumor necrosis factor alpha (TNF-alpha) were measured before the start of therapy and after 24 weeks. In addition serum IGF-1 and IGFBP-3 values were determined after 48 weeks. RESULTS: Twenty-seven HIV-1-infectedchildren with a median age of 5.5 years (range, 0.3 to 14.9 years) were included. Overall no significant changes in height and body mass index (BMI) z scores were observed. The median baseline plasma viral load of 68,800 copies/ml decreased to less than the detection limit of 500 copies/ml in 80% of the children after 48 weeks. TNF-alpha values were elevated (44 pg/ml) at baseline and decreased significantly to 37 pg/ml after 24 weeks. At baseline elevated TNF-alpha was observed in 78%, which decreased to 55% after 24 weeks. Baseline free thyroxine and cortisol values were normal and did not change during therapy. Baseline serum of IGF-1 and IGFBP-3 concentrations were normal, but IGF-1 tended to be lower than IGFBP-3. Both values increased significantly after the initiation of therapy. IGFBP-3 decreased after 48 weeks whereas IGF-1 stabilized. The increase in IGF-1 was significantly higher in children in whom the BMI and length (after correction for age and sex) increased the most. CONCLUSION:Hypothyroidism and adrenal axis abnormalities are not associated with restoration of growth after the initiation of antiretroviral therapy in HIV-1-infectedchildren. The combination of relatively high serum IGFBP-3 concentration and relatively lower serum IGF-1 suggests the presence of a growth hormone-resistant state. During treatment with a protease inhibitor-containing regimen, decreased serum IGFBP-3 and stabilization of IGF-1 after a significant initial increase suggest restoration of normal sensitivity to growth hormone and recovery to an anabolic condition.