Endocrinologic and immunologic factors associated with recovery of growth in children with human immunodeficiency virus type 1 infection treated with protease inhibitors.
BACKGROUND
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.


CONCLUSIONS
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.
Van Rossum
Annemarie M
AM
Division of Pediatric Infectious Diseases and Immunology, Department of Pediatrics, Erasmus MC/Sophia Children's Hospital, Rotterdam, the Netherlands.
Gaakeer
Menno I
MI
Verweel
Swenda
S
Hartwig
Nico G
NG
Wolfs
Tom F
TF
Geelen
Sibyl P
SP
Lamberts
Steven W
SW
de Groot
Ronald
R
D023241:Antiretroviral Therapy, Highly Active; D001827:Body Height; D015992:Body Mass Index; D018791:CD4 Lymphocyte Count; D002675:Child, Preschool; D005260:Female; D006128:Growth / Q000187:drug effects*; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis / Q000276:immunology; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000276:immunology; D008297:Male; D019888:Nelfinavir / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D012709:Serum Albumin / Q000032:analysis; D013974:Thyroxine / Q000032:analysis; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019562:Viral Load
D017320:HIV Protease Inhibitors; D018972:Insulin-Like Growth Factor Binding Protein 3; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D019888:Nelfinavir; D013974:Thyroxine; D006854:Hydrocortisone