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Alterations in regional fat, often associated with abnormalities in lipid and insulin metabolism, have been reported in HIV-infected adults. To determine whether similar abnormalities occur in children with HIV, patterns of change in regional body fat distribution were determined by dual energy x-ray absorptiometry in 28 prepubertal HIV-infected children. Eight (29%) children experienced lipodystrophy (LD), defined as extremity lipoatrophy together with trunk fat accumulation. Despite a mean body weight increase of 2.9 ± 2.4 kg, children with LD experienced a mean loss of total fat in contrast to children without LD who increased total fat (-0.151 ± 0.324 versus 0.981 ± 1.041 kg; p < .01). Children with LD had significantly higher levels of HIV RNA and lower CD4 count and percentage at baseline. LD was associated with use of protease inhibitors or stavudine, (odds ratio [OR], 7.0, 95% confidence interval [CI], 1.1-45.2, p = .04; OR, 9.0, 95% CI, 1.4-59.8, p = .03, respectively). This observational study suggests that during a time in childhood when accumulation of extremity and trunk fat is expected, some HIV-infected children experience changes in fat distribution that are similar to HIV-associated LD reported in adults. Studies to determine whether HIV-infected children with changes in regional fat also experience increases in “atherogenic” lipids and insulin resistance as described in adults with HIV-associated LD are warranted.