Insulin-Like Growth Factor-1 and Lean Body Mass in HIV-Infected Children

Chantry, Caroline J MD*; Hughes, Michael D PhD†; Alvero, Carmelita MS†; Cervia, Joseph S MD‡; Hodge, Janice BS§; Borum, Peggy PhD‖; Moye, Jack Jr. MD¶; for the PACTG 1010 Team

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e31817bbe6d
Clinical Science

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 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.

Author Information

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; ‖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.

Received for publication February 19, 2008; accepted April 1, 2008.

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:

Article Outline
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Poor growth1-5 and wasting6 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 children.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 longitudinal 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 disease10 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 in height and lean body mass would correlate positively with increases in IGF-1 and IGFBP-3 and with decreases in IGFBP-1.

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Subjects and Design

Pediatric AIDS Clinical Trials Group Protocol 1010 was a multisite, prospective 48-week cohort study of HIV-infected, prepubertal children aged 1 month to younger than 13 years who were beginning or changing ART. The ART criteria for inclusion incorporated one of the following scenarios: (a) beginning any ART if ART naive, (b) beginning protease inhibitor (PI)-based ART if PI naive, or (c) changing ART for virologic failure to a regimen including ≥2 new drugs. Exclusion criteria included the following: concurrent acute illness or fever within 14 days before entry; treatment within 180 days of entry with corticosteroids (unless ≤15 days total and not within the previous 14 days), anabolic steroids, megestrol acetate, interleukin, interferon, thalidomide, or GH; malignancy; pubertal development (Tanner Stage > 1); use of metal prostheses or implanted electrical devices; limb amputation; physical disability that would prevent a reliable assessment of height or length; and insulin-dependent diabetes. Ethics committee approval was obtained from each participating institution. Written informed consent from the parent or legal guardian and assent from the child when appropriate were also obtained. Accrual began in June 2000 and continued until March 2004.

Visits were at study entry (within 72 hours before ART initiation or change) and at 12, 24, 36, and 48 weeks thereafter. At each visit, the following evaluations were performed by trained staff: interim history and physical examination including Tanner staging, anthropometry [weight, height, circumferences (waist, hip, and limb) and skinfold thicknesses (triceps, thigh, and subscapular)], and 3-day diet record for protein and caloric intake (24 hours intake by recall if 3-day record not performed). Two distinct control cohorts were utilized as follows: (1) a large, nationally representative sample from which z scores for matched children could be derived [the National Health and Nutrition Examination Survey 1999-200211 (NHANES)] and (2) a control population which was more similar to the study population sociodemographically and included HIV-exposed, uninfected children from the Women and Infants Transmission Study12 (WITS) who were followed longitudinally. Growth and body composition measures {weight, length/height, body mass index (BMI), mid-thigh circumference (MTC), and mid-arm muscle circumference (MAMC) calculated as [mid-upper arm circumference − (triceps skinfold × 3.14)]} from study weeks 0, 24, and 48 were compared with z scores derived by selecting all available matched children in the NHANES database [of the same sex, race-ethnicity, and age (±3 months)] and then calculating the z score as (case's value − mean of matched controls)/(SD of matched controls). MTC was measured in NHANES only in children aged 8 years or older, limiting utility in our younger subjects. There was a mean (SD) number of matched controls from NHANES ranging from 36.3 (9.8) to 40.5 (12.9) for each study subject's different anthropometric measures, as not all measures were available in all children in Protocol 1010 or in NHANES. As noted above, growth and anthropometric data from 0 and 48 weeks were also compared with matched HIV-exposed, uninfected children from the WITS; in addition to matching criteria in NHANES, older WITS controls (females 7 years and older and males 9 years and older) were also matched to be Tanner Stage 1 at week 0. A total of 129 matches for 72 children (1-3 matched controls per case) were identified. As WITS had very few children older than 8 years, no matches for 22 of 38 children older than 8 years were identified, limiting utility in our older subjects. IGF-1, IGFBP-1, IGFBP-3 evaluations were not available in NHANES or WITS.

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Laboratory Analyses

Serum was collected from overnight fasting subjects for IGF-1, IGFBP-1, and IGFBP-3 quantification at each visit. Serum was stored under refrigeration and/or frozen conditions, as appropriate for each analyte, and tested in real time at Quest Diagnostics using their routine methodologies in place from 2001 to 2004.13 IGF-1 was quantified by a 2-site chemiluminescence immunoassay and IGFBP-1 and IGFBP-3 by radioimmunoassay. Analytic sensitivities of the assays are 0.1 and 5.0 ng/mL and 0.8 mg/L, respectively. For some subjects, available serum volume meant that some or all 3 of the measurements could not be obtained; they were prioritized after viral, immune, and metabolic analytes and in the order IGF-1, IGFBP-3, and IGFBP-1. Age- and sex-specific normal values were obtained from this laboratory for children aged 2 months and older for IGF-1 and IGFBP-3 and 5 years and older for IGFBP-1.14

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Statistical Analyses

McNemar test was used to evaluate changes over time in the proportion of children with serum IGF-1 and IGFBP-3 concentrations that were below, and IGFBP-1 concentrations above, sex- and age-specific normal values. Student t test was used to compare mean z score changes (or case-control difference in change) of growth and body composition measures among children whose IGF-1 and IGFBP-3 increased to the normal range vs remained stable or became low and whose IGFBP-1 decreased to the normal range vs remained stable or became high. Wilcoxon rank sum test was used to compare median ratio of caloric intake to estimated caloric need at entry for children with normal vs abnormal baseline IGF-1, IGFBP-1, and IGFBP-3 and at 48 weeks for children whose values had normalized vs those whose had not.

Multivariate analysis was used to measure associations between (a) baseline anthropometric measures and IGF-1, IGFBP-1, IGFBP-3 concentrations and (b) changes in anthropometric measures and changes in IGF-1 and IGFBP concentrations over 48 weeks, after adjusting for age, sex, and race-ethnicity. In the multivariate analysis, IGF-1 and binding proteins were treated as continuous variables. To evaluate potential bias introduced by missing specimens, baseline clinical characteristics were compared for children with and without available serum for analysis.

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One hundred five patients were recruited to achieve the desired sample size of 100, as 5 patients were found to be ineligible after study entry because of pubarche (n = 3), disallowed medication (n = 1), or withdrawal of consent before initial data collection (n = 1). Three additional patients were excluded, as the entry visit occurred subsequent to the change in ART, resulting in a final sample size for analyses of 97 evaluable subjects at baseline. Six patients subsequently withdrew from the study before the 48-week visit. Demographic and clinical characteristics of the study population are summarized in Table 1. The mean (SD) age at baseline was 5.9 (3.6) years with 54% female, 61% black, non-Hispanic, and 48% CDC Clinical Class A or N; mean CD4% was 24.8 (12.5) and mean HIV-1 RNA was 4.55 (0.89) log10 copies/mL corresponding to a geometric mean of 35,338 copies/mL. At baseline, 29% of subjects were ART naive and, in addition, 24% were PI naive. At both 24 and 48 weeks, slightly more than half of the children had HIV-1 RNA <400 copies/mL. When comparing children with and without available samples for analysis of IGF-1 and binding proteins, there was a trend toward younger and shorter children and those with higher CD4% counts to have missing specimens. These children were not, however, more stunted (height-for-age z score) or wasted (weight-for-height z score) than those with specimens available for analysis.

Mean (SD) concentrations of IGF-1, IGFBP-1, and IGFBP-3 at baseline and at week 48 are shown in Table 2, and number and percent of children with abnormal values of each at both time points are found in Table 3. Eighty-seven children had IGF-1 measurements at baseline including 21 (24%) with values below the lower limit of the normal range; none had values above the upper limit of the normal range. Compared with children with normal baseline IGF-1 concentrations, children whose IGF-1 concentration was low at baseline were older (median age 9.8 vs 5.4 years, P < 0.001) and had more advanced disease as measured by lower median CD4% (11.5 vs 27.0, P < 0.001) and higher median viral load (log HIV RNA 5.0 vs 4.5, P = 0.002) at baseline; there was no difference in the percent of children who were ART or PI naive vs exposed (P = 0.58 and P = 0.46, respectively). Anthropometric measurements demonstrated that they had lower mean z scores for weight (−1.20 vs −0.49), height (−1.95 vs −0.68), BMI (−0.77 vs −0.19), MTC (−1.42 vs −0.60), and MAMC (−1.72 vs −0.23) (Table 4). Infected children with low IGF-1 concentrations also showed greater mean deficits in each of these parameters vs their matched WITS controls than infected children with normal IGF-1 concentrations, though the difference was statistically significant only for height (−11.61 vs −3.22 cm, P = 0.004) and MAMC (−2.25 vs 0.10 cm, P = 0.001).

Sixty-nine children had IGF-1 measurements at both baseline and week 48. Eight of the 16 (50%) who had concentrations below normal at baseline had concentrations in the normal range at week 48, whereas only 1 of the 53 children with concentrations in the normal range at baseline showed a decline to below normal (P = 0.020; Table 2). The 8 children who normalized their IGF-1 had significantly greater median increase in CD4% (17.5%) than either the children who had low levels that remained low (2.0%) or those whose levels were initially normal and remained so (5.0%) (P = 0.010). There was, however, no difference in percent of children achieving viral suppression at 48 weeks (P = 0.24). Compared with the 61 children who did not show an increase in IGF-1 category, the 8 children whose IGF-1 concentration increased from low to normal demonstrated greater increase in muscle mass as measured by mean change in MAMC z score at 48 weeks (1.00 vs −0.03, P = 0.029) and mean difference in MAMC compared with matched controls from WITS (1.32 vs −0.22 cm, P = 0.024). They demonstrated lesser increase in height, however, compared with their uninfected WITS counterparts (−2.90 vs 1.09 cm, P = 0.003).

Multivariate analysis of associations between entry anthropometric measures and baseline IGF-1 concentrations provided similar results. Entry z scores (derived from NHANES controls) for weight, height, MAMC (P < 0.001 each), MTC (P = 0.002), and BMI (P = 0.010) were significantly and positively associated with IGF-1 concentration at baseline, as were case-control differences (derived from WITS controls) for weight (P = 0.008), height (P = 0.016), MAMC (P < 0.001), and MTC (P = 0.001), whereas those for BMI and mid-thigh muscle circumference did not reach statistical significance (P = 0.078 and 0.064, respectively). The largest effect was seen with MAMC, where the z score (95% confidence interval) increased 0.84 (0.44, 1.23) for each 100 ng/mL higher baseline IGF-1. Multivariate analysis of the association between z score change (95% confidence interval) at 48 weeks and change in IGF-1 concentrations demonstrated significantly greater increases in MTC (P = 0.020) and BMI (P = 0.025) with greater IGF-1 increases. Although the association with weight and MAMC failed to reach statistical significance (P = 0.059 and 0.057, respectively), the effect size with MAMC again was greatest with 0.32 (−0.01, 0.66) z score increase for every 100 ng/mL increase in IGF-1 at 48 weeks. In the corresponding analysis with WITS controls, no differences in anthropometric changes were significantly associated with changes in IGF-1 concentrations (data not shown).

Normal ranges for IGFBP-1 concentration were only available for children aged 5 years or older. Forty-two children in this age range had baseline measurements, including 23 (55%) who had concentrations above the upper limit of the normal range; only one child had a concentration below the lower limit of the normal range. Twenty-three children had both baseline and week 48 IGFBP-1 measurements. Nine of the 13 (69%) who had concentrations above normal at baseline had concentrations below the upper limit of the normal range at week 48, whereas only 2 of the 10 children with concentrations below the upper limit of the normal range at baseline showed an increase to above normal (P = 0.035; Table 3). In multivariate analysis, entry BMI z score was significantly and inversely associated with baseline IGFBP-1 concentration, P = 0.036; there were no other statistically significant associations with concentrations at either baseline or with changes in the concentration over time. Nor were there significant differences between infected children with abnormal vs normal concentrations of IGFBP-1 at baseline in baseline growth or body composition measures, though small numbers limit the power to evaluate differences. Finally, comparing children who showed declines from high to normal concentrations with those who did not show such changes revealed no significant differences in growth or body composition changes (data not shown).

Relatively few children had abnormal concentrations of IGFBP-3 at any point in time. At baseline, only 5 of the 67 children with measurements (7%) had concentrations below normal, and among the 37 children with both baseline and week 48 measurements, only one child showed an improvement from below normal to normal and 2 children showed decreases from normal to below normal. Because of the very small number of children with abnormal IGFBP-3 concentrations, growth and body composition measures were not compared for children with abnormal vs normal concentrations. In multivariate analysis, there were significant associations between weight (P = 0.006), height (P < 0.001), MAMC (P = 0.002), and MTC (P = 0.012) z scores at entry and baseline concentrations of IGFBP-3, but anthropometric changes were not associated with changes in IGFBP-3 concentrations.

There was no significant difference in median ratio of caloric intake to estimated caloric need between children with abnormal vs normal concentrations of IGF-1 or IGFBP-1 or IGFBP-3 at entry (P = 0.15, 0.88 and 0.79, respectively) or between those whose IGF-1 or IGFBP-3 levels remained low vs increased to normal (P = 0.37, 1.00). There was, however, a significantly greater median ratio of intake to need among subjects whose IGFBP-1 level was initially high and decreased to normal vs those whose IGFBP-1 remained high, 1.04 vs 0.68, P = 0.021.

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The novel findings in this study are two-fold: a) in children whose IGF-1 was initially low and became normal there was an associated increase in muscle mass (specifically MAMC) compared both with population norms and comparable matched controls of uninfected children born to HIV-infected mothers; and b) a high proportion of children had abnormally high IGFBP-1 concentrations at study entry which decreased to normal over time. Decreased IGF-1 has been noted in multiple studies to be associated with failure to thrive in children with HIV infection,15,16 but changes in muscle mass have not heretofore been associated with longitudinal improvements in IGF-1. Although improvements in mean MAMC z score were seen when an abnormally low IGF-1 became normal, the association between mean MAMC z score increase and increases in IGF-1 was only of marginal significance in multivariate analysis when evaluating anthropometric changes in all the study children. This difference may relate to the wide range of normal values obscuring changes of more physiological significance.

In this study, normalization of IGF-1 was associated with lesser height improvement compared with WITS controls, in contrast with findings previously reported in a smaller cohort.8 Of note, all 6 of the children included in the WITS case-control comparison who normalized their IGF-1 levels were markedly stunted at the beginning of the study and did grow over the 48 weeks of observation but less so than did their uninfected matched controls, certainly not demonstrating catch-up growth. We did not note the increases in IGFBP-3 described in a prior study.8 Speculatively, the latter difference may be due to the uniform use of PI therapy in that study, which may have a specific effect on proteolysis of IGFBP-3.

Our findings lend credence to the theory that alterations in GH sensitivity may be fundamental to the improved anabolism that may be seen upon initiation of highly active antiretroviral therapy. It is not clear why the improved GH sensitivity was reflected in improved limb muscle mass and not in linear growth. Perhaps, early in the anabolic response, protein accretion is first directed toward diminished muscle mass and subsequently toward linear growth such that a longer study may have demonstrated an association between IGF-1 and greater height increases. Alternatively, a persistent deficit in linear growth may reflect a persistent endocrine abnormality, such as IGF-1 resistance, despite a normalized concentration of IGF-1.

IGFBP-1 inhibits IGF-1 by rendering it unavailable to receptors; its expression increases in catabolic states,17 and it is a marker for insulin resistance. To our knowledge, this binding protein has not previously been evaluated in childhood HIV disease, but adult AIDS patients with vs without wasting have increased levels.18 Hepatic production of IGFBP-1 is stimulated by multiple cytokines, including interleukin-1,19,20 interleukin-6,21 and tumor necrosis factor alpha.22 The potential importance of elevated IGFBP-1 in many of the HIV-infected children in this study is underscored by multiple reports that note an association between increased mortality rates and IGFBP-1 levels in diverse disease states, such as meningococcal sepsis in children23 and cardiovascular disease in elderly men.24 Investigation of IGFBP-1 as a prognostic marker in HIV infection may be warranted. It is possible that the elevated IGFBP-1 found in our study contributes to decreased growth and lean body mass in these children, despite the fact that we did not detect more wasting or stunting in children with higher levels at entry or improved linear or ponderal growth in children whose IGFBP-1 levels diminished during the study as we had hypothesized. This may be due to limited power as normal ranges for IGFBP-1 were only available for children aged 5 years or higher, and limited serum sample volume restricted IGFBP-1 testing such that only 42 children in this age range had measurements at baseline. It is also possible that the decrease in IGFBP-1 seen in this study may be secondary to an increase in insulin resistance induced by the initiation or change in ART. We previously reported that mean insulin levels significantly increased over the 48 weeks in this population,25 but insulin resistance was only abnormal in 3% of the children at 48 weeks, quite disparate from the change in abnormal IGFBP-1 concentration from 55% to 20% of the children studied. Lastly, it may be that the decrease in IGFBP-1 was a result of improved nutritional status in the children whose level normalized, as suggested by the significant difference in median caloric intake relative to estimated need between children whose level remained abnormal vs those that decreased to normal. We would expect, however, that if poor nutrition was the primary cause of elevated IGFBP-1 in these children, then there would also have been a significant difference in intake at baseline between children with normal vs abnormal values, which was not the case.

There are several limitations to this study. It is likely that the HIV-infected children in our study differed from the overall US population represented in NHANES data in ways for which we could not adjust, such as socioeconomic status, parental health, and so on. In addition, NHANES is a cross-sectional study and therefore not an ideal comparison group for longitudinal growth data. The HIV-exposed, uninfected cohort in WITS are likely to be more similar to our study population than the overall population in NHANES and had the additional advantage of having anthropometric measurements in young children, but there were very few matches for the older children and a sample size that did not allow for generation of z scores. Measures of body composition were limited to anthropometric measures, with only muscle circumferences to evaluate lean body mass. Although muscle circumference measures are clinically significant and accurately reflect regional muscle mass, there are more accurate techniques to measure overall lean body mass. Accordingly, lack of associations between the GH axis and lean body measures in this study should not be regarded as conclusive. Furthermore, we did not have a comparison group of HIV-infected children who were not beginning or changing ART, so clearly the changes in IGF-1 and binding proteins noted are not necessarily causally related to the ART. Similarly, the association between abnormally low IGF-1 levels becoming normal and improved anabolism does not demonstrate causality. Finally, the sample volume was limiting for many children such that 10%, 31%, and 57% of children at baseline had missing IGF-1, IGFBP-3, and IGFBP-1 results, respectively. Given the trend toward children who were younger, shorter, and had higher CD4% cell counts to have missing data, these findings may not fully represent the children in Protocol 1010. The major strengths of the study include a sample size larger than other prospective studies evaluating IGF-1 and binding proteins in a population of growing children, anthropometric measures other than height and weight, inclusion of IGFBP-1, and evaluation before and after initiation or change in multidrug combination ART.

Finally, the findings in our study may have therapeutic implications for HIV-infected children with persistently diminished muscle mass. The anabolic response that was associated with normalized IGF-1 during the study and the high proportion of children who concomitantly experienced normalization of IGFBP-1 suggest that recombinant IGF-1 or anticytokine therapies may merit evaluation as potential treatment strategies for prepubertal HIV-infected children with poor muscle mass resistant to other interventions. To our knowledge, there have been no such trials. Published randomized trials of IGF-1 for wasting in HIV-infected adults have given combined IGF-1 and GH with mixed results.26,27 Thalidomide, an inhibitor of tumor necrosis factor alpha, has been found effective for HIV-associated wasting in adults;28 perhaps, the mechanism is via reduction of IGFBP-1 levels.

In summary, in this population of HIV-infected children predominantly with mild to moderate disease, IGF-1 concentrations were associated with more robust baseline growth and body composition, and children whose IGF-1 concentrations became normal demonstrated improved anabolism over time. A high proportion of children had abnormally high IGFBP-1 levels that decreased upon initiation or change in ART. These findings provide further evidence that alterations in the GH axis commonly affect growth and body composition adversely in childhood HIV infection and suggest potential therapeutic strategies for HIV-infected children with poor muscle mass.

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The authors would like to acknowledge the children who participated in this study and their families, the entire Protocol 1010 team for their contributions and support, and Jie Chin for statistical support. We are also grateful to the Women and Infant Transmission Study for sharing data on matched, uninfected children. We acknowledge W.A. Meyer III, Quest Diagnostics, Baltimore, for his assistance in coordinating the laboratory analyses and review of this manuscript.

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The following sites and individuals have contributed to this study: Howard University: S. Rana, P. Yu, S. Dangol, J. Roa; Bronx Lebanon Hospital Center; St. Jude Children's Hospital: M. Donohoe, K. Knapp, N. Patel, J. Utech; Baylor Texas Children's Hospital: K. Owl, M. Dobmeier, M. Paul, C. Hanson; Children's Hospital of Boston, Harlem Hospital: E. Abrams, D. Calo, M. Fere, S. Champion; North Broward Hospital District, Jacobi Medical Center: A. Wiznia, M. Chin, K. Dorio, J. Abadi; University of Florida: J. Sleasman, R. Lawrence, C. Delaney; Children Hospital of LA: T. Dunaway, L. Heller; University of Maryland: J. Farley, M. MacFadden; State University of New York at Stony Brook: S. Nachman, M. Davi, C. Seifert, S. Muniz; Metropolitan Hospital Center: M. Bamji, I. Pathak, S. Manwani; Children's Hospital, Oakland: A. Petru, T. Courville, K. Gold, S. Bessler; Harbor-UCLA Medical Center: M. Keller, K. Zangwill, J. Hayes, A. Gagajena; Columbia Presbyterian Medical Center: A. Higgins, M. Foca; University of Miami: C. Goldberg, M. Bissainthe, C. Mitchell, G. Scott; New York University School of Medicine: T. Hastings, M. Mintor, N. Deygoo, W. Borkowsky; University of Illinois: K. Rich, K. Hayani, J. Camacho; Children's Hospital University of Colorado, Denver: E. McFarland, M. Levin, C. Salbenblatt, E. Barr; Medical College of Georgia: W. Foshee, C. Mani, C. White, B. Kiernan; Johns Hopkins University: S. Marvin, A. Ruff; Duke University: R. McKinney, Y. Choi, L.Ferguson, J. Swetnam; Children's National Medical Center, San Juan City Hospital: M. Acevedo, M. Gonzales, C. Martinez Betancoult, F. Pabon; Yale University School of Medicine: D. Schroeder, S. Romano, M. J. Aquino-de Jesus; Los Angeles County Medical Center: J. Homans, Y. Rodriquez, A. Kovacs; University of Puerto Rico: I. Febo Rodriquez, L. Lugo, I. Heyer, C. Martinez; University of Massachusetts Medical School.


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

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