Pediatr Infect Dis J, 2003;22:77–84 Vol. 22, No. 1 Copyright © 2003 by Lippincott Williams & Wilkins, Inc. Printed in U.S.A. Metabolic complications of antiretroviral therapy in children ETHAN G. LEONARD, MD AND GRACE A. MCCOMSEY, MD Survival in HIV-infected children has greatly improved with the introduction of highly active antiretroviral therapy. Children are more vul- nerable than adults to metabolic side effects of therapy because of its potential impact on growth and the children’s likely greater cumula- tive exposure. This review summarizes the epi- demiology and management of lipodystrophy, dyslipidemia, insulin resistance, hyperlac- tatemia, osteopenia and growth failure in HIV- infected children. INTRODUCTION The implementation of potent antiretroviral drugs in combination regimens has profoundly decreased mor- tality and disease progression in HIV-infected pa- tients. 1 Concomitantly morbidity from the long term effects of antiretroviral therapy has grown in impor- tance. Among all these complications, lipodystrophy syndrome, mitochondrial toxicity and more recently osteopenia are the most concerning side effects of prolonged antiretroviral therapy. The adult medical literature contains many studies and reports about these complications. This review discusses each of these abnormalities separately in an attempt to sum- marize the current understanding of their pathogene- sis and management with a focus on HIV-infected children. LIPODYSTROPHY Although recognized since 1996, HIV-associated lip- odystrophy syndrome remains controversial in its def- inition and mysterious in its etiology. A variety of terms describe this syndrome in terms of its clinical manifestations or its postulated etiologies: “the fat redistribution syndrome,” “truncal obesity syndrome,” “buffalo hump,” “symmetric lipomatosis,” “protease paunch” and “Crix belly.” 2 Recently lipodystrophy syn- drome has been reported in HIV-infected children. 3, 4 Estimates of its prevalence among HIV-infected adults range from 2 to 84% 5 and from 1 to 43% 6 of HIV- infected children, likely reflecting the lack of standard- ized definitions for the features of this syndrome. The lipodystrophy syndrome involves body fat maldistribu- tion as well as the metabolic alterations of hyperlipid- emia and insulin resistance. Affected individuals dem- onstrate differing combinations and severity of these derangements. Each of these derangements is dis- cussed separately. FAT MALDISTRIBUTION Despite the confusing nomenclature the morphologic changes of lipodystrophy syndrome have been consis- tently described. In decreasing order of frequency, patients present with peripheral loss of adipose tissue (lipoatrophy), central gain in adiposity (lipohypertro- phy) or both features (mixed syndrome). Various means of assessing these changes have been reported. Patients often are the first to identify the symptoms by noting changes in their facial features or tightness of clothing. 7, 8 Various objective techniques to assess the changes in body fat content and distribution have been utilized including bioelectrical impedance, 9 anthropo- metric measurements, 5, 10 dual energy X-ray absorpti- ometry (DEXA), 5, 11 and abdominal computed tomogra- phy or magnetic resonance imaging (MRI). 12, 13 Bioelectrical impedance provides useful information about lean body mass and total body fat but not regional fat distribution. Caliper measurements assess only subcutaneous fat. DEXA provides information about regional fat distribution, except for the face. Only computed tomography or MRI scanning discriminates between subcutaneous fat stores and visceral fat. Pa- tients with lipodystrophy often have significant central obesity, but their subcutaneous abdominal fat is signif- icantly lacking whereas visceral stores are markedly increased. Increased visceral fat has clearly been asso- ciated with increased risk of coronary artery disease as well as insulin resistance. 14, 15 These body habitus changes are not only esthetically distressing to pa- tients but also predispose them to future cardiovascu- lar diseases and type II diabetes mellitus. These Accepted for publication Sept. 20, 2002. From the Division of Pediatric Infectious Diseases, Rainbow Babies and Children’s Hospital (EGL, GAM), and the Center for AIDS Research, Case Western Reserve University (GAM), Cleve- land, OH. Key words: Lipodystrophy, dyslipidemia, insulin resistance, hyperlactatemia, mitochondrial toxicity, osteopenia. Address for reprints: Dr. Grace A. McComsey, Division of Pediatric Infectious Diseases, Rainbow Babies and Children’s Hospital, 11100 Euclid Avenue, Room 487, Cleveland, OH 44106. Fax 216-844-8362; E-mail mccomsey.grace@clevelandactu.org. 77