There is evidence that children with HIV infection are at risk for body fat redistribution (lipodystrophy), in patterns similar to those seen in HIV-infected adult patients. However, there are few known interventions to prevent or control abnormal body composition and metabolic profiles in HIV-infected children exposed to highly active antiretroviral therapy. Our study group at the University of Rochester examined the cases of 2 HIV-infected children who underwent exercise training as part of an exercise rehabilitation program to determine whether progressive resistance and aerobic training was safe and feasible and could augment strength; improve body mass index; and reduce total, subcutaneous, and visceral adiposity. EXERCISE REHABILITATION PROGRAM METHODOLOGY The program consisted of a 2-day assessment of growth and body composition before the start of training. Heights and weights, adjusted for age and sex and expressed as z scores,1 were used to determine growth. Body composition was evaluated using several techniques, including dual-energy x-ray absorptiometry (DXA) to determine whole-body and regional lean and fat mass and measurement of skin-fold thickness at 4 body sites. A single sagittal CT scan was obtained at the level of the midpoint of the L4-5 intervertebral space, and the images were analyzed with a computerized image analysis system to determine visceral, subcutaneous abdominal, and total abdominal fat. HIV RNA level and CD4 counts were measured by standard methods in the clinical laboratory. On the second day, baseline peak oxygen consumption was assessed with a metabolic exercise stress test. Baseline 1-repetition maximum (1-RM) was determined on 8 pieces of pediatric weight training equipment (chest press, triceps extension, bicep curl, pec dec [pectorals], shoulder press, leg curl, leg extension, and lat pull down). Grip strength and flexibility were also measured. Following the pretraining assessments, the children completed a 12-week program in which they incrementally increased work capacity on each piece of equipment with close supervision and instruction by the exercise physiologist. The sessions were 1 to 1.5 hours, twice weekly. More time was allowed, as needed, for the patients to complete the exercise regimen. The children received their normal nutritional counseling through the Pediatric Infectious Disease Program. There was no specific parental counseling. At the end of the 12 weeks, the children underwent testing identical to the 2-day baseline evaluations by the same exercise physiologist. The children were given instruction at the completion of their 3-month program to continue using a home-based exercise program developed specifically for each of them. Weekly calls from the exercise physiologist ensured continued training. The children were to be evaluated 3 months after completion of the program to determine whether results could be maintained with the home-based program. The Human Subjects Review Board at The University of Rochester Medical Center, Rochester, NY, approved the program, and the legal guardians of the participants gave their consent. CASE SUMMARIESPatient 1 A 10-year-old girl with perinatally acquired HIV infection (CDC category B22) underwent 12 weeks of progressive resistance exercise training with an aerobic component because of personal motivation to adopt a healthier lifestyle. Her stable antiretroviral regimen included stavudine, nevirapine, and nelfinavir; this did not change over the 12 weeks of training. At the start of training, she had no evidence of clinical lipodystrophy, she was growing well, and her fasting lipid profile and glucose and insulin levels were normal. Patient 1 completed the 3-month program on schedule. Her absolute CD4+ cell count decreased from 540/µL to 404/µL. Paradoxically, the HIV RNA level decreased from 14,589 copies/mL to 3980 copies/mL. Body mass index (BMI) decreased 4% (from 20 kg/m2 to 19.3 kg/m2). Triceps skin-fold thickness percentage (adjusted for age and sex) decreased from 76% to 69%. Suprailiac, subscapular, and biceps skin-fold thicknesses also decreased, 17%, 9%, and 9%, respectively. Body fat and trunk fat as measured by DXA also decreased, 9% and 10%, respectively. Single-slice CT evaluations of total, subcutaneous, and visceral abdominal adiposity are shown in the Table and Figure 1. Total abdominal area (-8%) and abdominal total (-19%), subcutaneous (-19%), and visceral (-23%) fat area all decreased after completion of the 3-month training program. The ratios of visceral to subcutaneous adipose tissue (-5%) and abdominal total adipose tissue to visceral fat (4%) all showed improvement with decreased visceral fat. Figure 1.Change from start of exercise training to 3-month follow-up as assessed by single-slice CT scan evaluation of abdominal total adipose tissue (TAT), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) in each patient. Maximum oxygen consumption had increased 14% at completion of the 3-month program, suggesting improved cardiovascular conditioning. Figure 2 shows percent change in muscle strength for select pieces of equipment over the 3 months of training. Muscle strength improved in all muscle groups, except for the shoulder press; the improvements that were seen ranged from 10% to 40%. Figure 2.Change in strength from start of exercise training to 3-month follow-up for selected resistance exercises. Seven months after completion of the program (logistical issues prevented the scheduled 3-month follow-up), maximum myocardial oxygen consumption had increased 28% over baseline, and repeated measurements of skin-fold thickness, obtained by the same observer, showed an overall decrease of 8% compared with the measurements taken at the start of training. BMI was stable, and 1-RM measurements showed that this patient's strength continued to be higher than was recorded before training (from a 2% to 75% increase). Patient 2 A 17-year-old girl with perinatally acquired HIV infection (CDC category B32) underwent the same 12-week training program as Patient 1 because of increased BMI (27.2 kg/m2) and increased body fat (43%). Her stable antiretroviral regimen included zidovudine, lamivudine, and nelfinavir; this did not change during the training period. Before the training program, she had no clinical evidence of lipodystrophy beyond increased body fat, and her fasting lipid profile, glucose level, and insulin level were normal. Like Patient 1, Patient 2 also completed the 12-week exercise program on schedule. Her HIV RNA level was undetectable before training and continued to be undetectable during the 3-month program. After 3 months, her BMI decreased from 27.2 kg/m2 to 26.1 kg/m2 (4% decrease). Although triceps skin-fold thickness percentage increased from 85% to 92%, other skin-fold measures of adiposity decreasedsuprailiac by 34%, subscapular by 27%, biceps by 10%-at the completion of the 3-month program. DXA mea-sures of adiposity remained relatively stable in this patient (total fat, 43% to 45%). However, more sensitive measures of total, subcutaneous, and visceral abdominal adiposity by single-slice CT scanning showed all measures decreased by 20%, 21%, and 3%, respectively, after completion of the 3-month training program (Table and Figure 1). This patient did not show improvement in maximum oxygen consumption after the training program. Figure 2 shows percent change in muscle strength for select pieces of equipment over the 3 months. Patient 2 had a greater increase in muscle strength than Patient 1 in most muscle groups: a 22% to 64% increase, depending on the muscle group. Three months after completion of training, maximum myocardial oxygen consumption remained the same, and repeated measurements of skin-fold thickness showed an overall decrease of 14% compared with measurements taken before training. BMI decreased an additional 4%, and 1-RM measurements showed continued improvements. DISCUSSION It is well documented that exercise can promote healthy outcomes for adults who engage in it regularly. These effects are appreciated in lower rates of cardiovascular disease,3 decreased osteoporosis in women,4 improved function in those with rheumatoid arthritis,5 and lowered risk of diabetes,6 to name a few. There is currently an interest in exercise programs for children, with the recognition that early institution of healthful habits in children may have positive behavioral effects later in adulthood, when physical activity usually declines.7,8 In general, studies have shown that physical exercise has positive influences on the growth and maturation of children.9 Active children, compared with inactive peers, have higher scores on strength, motor, and cardiovascular fitness tests.9 It is unclear whether this is a cause or a consequence of greater physical activity. Age, sex, and socioeconomic status also influence physical activity, with greater activity in boys, children of higher socioeconomic status, and older children.10 Exercise can increase bone mineral density over and above the effect on body weight in prepubescent and adolescent girls.11 Specific programs designed to improve strength, flexibility, and endurance in healthy children have been studied and appear to be safe in children as young as 6 years.12,13 Even before the recognition of lipodystrophy, exercise programs for adults with HIV infection showed promise in improving nutritional and functional outcomes.14,15 Other studies showed improvements in weight, with a greater than expected percent increase in lean body mass.16-18 Furthermore, controlled training programs in HIV-infected patients have not decreased CD4 counts or increased cytokine activation.17,19,20 Pulmonary function studies in adults with HIV infection revealed lower workload, lower anaerobic threshold, and decreased oxygen utilization compared with those in adults in an age-matched control group.14 These parameters can be improved with aerobic training in HIV-infected adults.15 Exercise training programs also have been shown to control or reverse lipodystrophy in adults.21-23 Children with chronic illness are likely to have decreased physical activity, less muscle strength, decreased aerobic capacity, and overall deconditioning. In HIV-infected children, we have shown an overall decline in lean body mass, nutritional state,24,25 and functional status over time.26 Moreover, highly active antiretroviral therapy may predispose children to the chronic problems of abnormal lipid metabolism, fat redistribution, and insulin resistance. It is therefore important to determine whether exercise programs are feasible, practical, and effective in HIV-infected children with and without metabolic concerns. Here, the use of a medically supervised 12-week aerobic and resistance training program proved to be feasible, safe, and effective in improving strength and flexibility in 2 HIV-infected patients. Of importance, we found that the improvements in strength, body composition, and BMI were sustained at home (through a home-based program) for months following the more intensive hospital-based exercise program. Although there are no normal standards for subcutaneous and visceral adiposity as measured by CT scanning in children, we found that a 3-month program decreased these measures. Central adiposity, a feature often found in lipodystrophy associated with highly active antiretroviral therapy, is a known risk factor that can contribute to long-term adverse metabolic and cardiac outcomes in adults.27 The children had normal lipid, glucose, and insulin values before the training program, thus we could not assess the response within these metabolic parameters. The HAART era has brought effective treatment for control of HIV infection in many patients, yet unwanted sequelae have appeared. While protease inhibitor therapy can have a positive effect on growth and lean body mass in children,28 lipodystrophy associated with antiretroviral therapy has been well described in both adult and pediatric populations.29-35 The long-term consequences of hyperlipidemia, trunk adiposity, and insulin resistance are well known in non-HIV populations.27 In addition, data show that these biochemical abnormalities translate into increased atherosclerotic cardiovascular risk, with greater than normal rates of myocardial infarction36,37 and stroke38 among HIV-infected adults. Similar data are not yet available in children, since the length of follow-up time has not been sufficient. Physical activity and training programs can reverse abnormal metabolic and cardiovascular parameters in other chronic illnesses,39 and data showing the same in HIV-infected adults are emerging.21-23 Although drug trials using recombinant human growth hormone, testosterone, and hypoglycemic agents to reverse lipodystrophy are under way, these medications have adverse effects, and studies of their safety and efficacy in children have been limited. Physical activity programs require no medications and have the potential to initiate lifelong positive healthful behaviors for children. Although the data presented here are from only 2 cases, the positive effects of aerobic and strength resistance training in these children were evident. Although both children derived benefits from the training program, their age difference, reflecting different stages in puperty, may account for the degree of changes in strength and body composition. In light of the potential nutritional and metabolic complications associated with HIV infection, these interventions in children may have the potential for widespread impact, especially if the training programs can be conducted in programs close to home. For children with HIV infection and malnutrition, few interventions thus far have been shown to improve body composition and other functional outcomes.40,41 Furthermore, the data are limited on therapies to reverse the body composition and metabolic abnormalities in HIV-infected children with lipodystrophy associated with antiretroviral therapy; strength resistance and aerobic training has the potential to improve both of these conditions. On the basis of our encouraging preliminary findings, progressive resistance training programs for children with HIV infection, especially those with clinically apparent lipodystrophy and abnormal metabolic profiles, should be pursued. Acknowledgment: The University of Rochester Study Group investigators include Sara Horgan (exercise physiologist), Jeanne Nicchitta (research dietician), and Tina Lipinczyk (research associate). This work was supported in part by NIH grants P01DK45734 and 5M01RR02172. No potential conflict of interest relevant to this article was reported by Dr Miller. References: References1. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, et al. CDC growth charts: United States. Adv Data. 2000;314:1-27. 2. Centers for Disease Control and Prevention. 1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age. MMWR. 1994;43:1-10. 3. Erikssen G, Liestöl K, Björnholt J, et al. Changes in physical fitness and changes in mortality. Lancet. 1998;352:759-762. 4. Shangold MM. Exercise in the menopausal woman. Obstet Gynecol. 1990;75(4 suppl):53S-58S. 5. Bell MJ, Lineker SC, Wilkins AL, et al. 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