CLINICAL SCIENCE Insulin-Like Growth Factor-1 and Lean Body Mass in HIV-Infected Children Caroline J. Chantry, MD,* Michael D. Hughes, PhD,† Carmelita Alvero, MS,† Joseph S. Cervia, MD,‡ Janice Hodge, BS,§ and Peggy Borum, PhD, k and Jack Moye, Jr., MD¶ for the PACTG 1010 Team Objectives: 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 concen- trations 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 20.03, 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. Key Words: HIV, insulin-like growth factor-1, growth, body composition, lean body mass, children, binding proteins, IGF-1– binding protein-1, IGF-1–binding protein-3 (J Acquir Immune Defic Syndr 2008;48:437–443) INTRODUCTION Poor growth 1–5 and wasting 6 are common manifestations of HIV infection and AIDS in children; stunting in particular may not resolve even with the administration of highly active antiretroviral therapy. 7,8 The pathophysiology of these growth abnormalities is incompletely understood, although evidence is accumulating that HIV-infected children have growth hormone (GH) resistance relative to HIV-uninfected chil- dren. 8,9 Lower insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-1–binding protein-3 (IGFBP-3) levels have been noted in HIV-infected children with impaired growth. 9 It is unclear whether improved growth sometimes seen with antiviral treatment is primarily a physiologic result of immune restoration, viral suppression, or yet another mechanism such as restored GH action. Although multiple reports describe associations of attained growth and the GH axis in childhood HIV infection, fewer data examine longi- tudinal changes. Finally, IGFBP-1, which is known to inhibit somatic linear growth and weight gain, has been shown to be associated with growth failure in other chronic conditions such as end-stage liver disease 10 but has not been examined in HIV- infected children. The objectives of this study were (a) to describe the levels of IGF-1, IGFBP-1, IGFBP-3 in HIV-infected children before and after initiating or changing antiretroviral therapy (ART) and (b) to evaluate association of growth and body composition measures to growth factors at baseline and over a 48-week time period. We hypothesized that greater increases Received for publication February 19, 2008; accepted April 1, 2008. From the *Department of Pediatrics, University California Davis Medical Center, Sacramento, CA; †Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; ‡Departments of Internal Medicine and Pediatrics, Albert Einstein College of Medicine, Bronx, NY; §Frontier Science & Technology Research Foundation, Amherst, NY; k Departments of Food Science and Human Nutrition and Pediatrics, University of Florida, Gainesville, FL; and the {National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. Supported in part by the Pediatric AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases and the Pediatric/Perinatal HIV Clinical Trials Network of the National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. Correspondence to: Caroline J. Chantry, MD, Department of Pediatrics, University of California Davis Medical Center, 2516 Stockton Boulevard, Sacramento, CA 95817 (e-mail: caroline.chantry@ucdmc.ucdavis.edu). Copyright Ó 2008 by Lippincott Williams & Wilkins J Acquir Immune Defic Syndr  Volume 48, Number 4, August 1, 2008 437 Copyright © 2008 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.