Insulin-like growth factor-1 and lean body mass in HIV-infected children.
OBJECTIVE
To describe insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-1-binding protein-1 (IGFBP-1) and IGFBP-3 in HIV+ children before and after initiating or changing antiretroviral therapy and to evaluate association of growth and body composition to growth factors at baseline and over time.


METHODS
Ninety-seven prepubertal HIV+ children aged 1 month to younger than 13 years were observed over 48 weeks after beginning or changing antiretroviral therapy. Serum IGF-1, IGFBP-1, and IGFBP-3 were measured and compared with age- and sex-specific norms. Anthropometric measures were compared as follows: subjects vs matched children from (a) the National Health and Nutrition Examination Survey to generate z scores and (b) HIV-exposed, uninfected children from Women and Infants Transmission Study; and subjects with normal vs abnormal IGF-1 and IGFBP concentrations at baseline. Anthropometric changes were compared for children whose IGF-1 level normalized vs remaining subjects. Multivariate analysis adjusting for sex, race, and baseline age evaluated associations between anthropometry and IGF-1 and IGFBP concentrations.


RESULTS
In multivariate analysis, lower baseline IGF-1 and IGFBP-3 were associated with lower mean weight, height, mid-arm muscle circumference, and mid-thigh circumference z scores. Twenty-four percent of children had a low IGF-1 level at baseline, 50% of whom normalized IGF-1 on study. Children whose IGF-1 normalized had greater increases in mean mid-arm muscle circumference z score (1.00 vs -0.03, P = 0.029), but a trend toward lesser mean height increase (P = 0.082) than remaining subjects. Likewise, in comparison to controls from Women and Infants Transmission Study, mean mid-arm muscle circumference also increased more in children whose IGF-1 normalized (P = 0.024) but mean height changed less (P = 0.003). Fifty-five percent of children had elevated IGFBP-1 at baseline, 69% of whom normalized.


CONCLUSIONS
IGF-1 increases and IGFBP-1 decreases in HIV-infected children upon initiation or change in antiretroviral therapy. Improved muscle mass, but not linear growth, is associated with normalized IGF-1 concentration. These findings suggest that IGF-1 may merit evaluation as a potential therapeutic strategy to improve lean body mass in HIV-infected children.
Chantry
Caroline J
CJ
Department of Pediatrics, University of California Davis Medical Center, 2516 Stockton Boulevard, Sacramento, CA 95817, USA. caroline.chantry@ucdmc.ucdavis.edu
Hughes
Michael D
MD
Alvero
Carmelita
C
Cervia
Joseph S
JS
Hodge
Janice
J
Borum
Peggy
P
Moye
Jack
J
D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D001827:Body Height; D001835:Body Weight; D002648:Child; D002657:Child Development / Q000187:drug effects; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006128:Growth; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D015497:HIV-1; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D015999:Multivariate Analysis; D016896:Treatment Outcome
D044966:Anti-Retroviral Agents; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I