Body fat changes and lipodystrophy in HIV-infected children: impact of highly active antiretroviral therapy.

To the Editor: HIV infection is a major cause of morbidity and mortality worldwide. In developed countries, life expectancy has increased considerably since the introduction of highly active antiretroviral therapy (HAART) in 1996. However, a number of reports have documented some unexpected adverse effects from HAART, including a group of conditions characterized by altered lipid and glucose metabolism and alterations in body fat distribution in patients receiving combination antiretroviral therapy. Clinical presentations have included the accumulation of adipose tissue in the dorsocervical region, commonly referred to as buffalo hump; fatty infiltration and bulging of supraclavicular fat pads, called Madelung disease; visceral abdominal fat accumulation (Bcrix belly^); benign symmetric lipomatosis; and subcutaneous fat wasting of the face and limbs. The pathogenesis of body fat redistribution and metabolic changes occurring among HIV-infected patients treated with antiretroviral therapy remains obscure. The lipodystrophy syndrome was initially described in the adult HIV-infected population and was thought to be associated with the use of the protease inhibitors (PIs). However, more recent studies (also in adults) have strongly suggested a role for nucleoside reverse transcriptase inhibitors (NRTIs) in the alteration of body fat distribution. Treatments combining a PI and NRTI increase the incidence and severity of the lipodystrophy syndrome. Although the lipodystrophy syndrome has been well characterized in the adult population, there are few pediatric data available. We therefore studied children with perinatally acquired HIV infection to examine the effect of HAART on body fat distribution, as assessed by measurements of limb and waist circumference and skinfold thickness in a crosssectional observational study. We studied HIV-infected children older than 3 years attending the HIV Family Clinic at Great Ormond Street Hospital National Health Service Trust, London, UK, in November 2002 to 2003. Of the 107 HIV-infected children identified as eligible for the study, 98 agreed to participate. All children included were classified according to the Centers for Disease Control and Prevention (CDC, Atlanta, GA) revised classification system for HIV infection in children. Clinical details and therapy history were extracted from the patient’s medical records. All children had a general physical examination, including specific observation for the presence of clinical features of altered body fat distribution (peripheral lipoatrophy: sunken cheeks, skinny arms, and legs with prominent veins; central lipohypertrophy: increased abdominal girth, Bbuffalohump,^ and breast enlargement). Blood samples and anthropometric measurements were also taken at the same visit. The latter included weight and height measurements and body mass index (BMI). Because these values vary with age, they were converted to ageand sex-adjusted z scores based on the British 1990 reference. Skinfold measurements (triceps, biceps, subscapular, and suprailiac) were measured using the Harpenden skinfold caliper (Holtain Ltd, Crymych, UK). Upper arm, waist, hip, thigh, and calf circumferences were measured using a narrow 1-m tape. All skinfolds and circumference were measured by the same trained researcher (A.D.). Waist circumference measurements were converted to ageand sex-adjusted z scores based on UK data. Values for skinfold measurements were converted to ageand sex-adjusted z scores with the use of Dutch reference curves using an SPSS program developed at the Institute of Child Health, University College London. Variables were tested for normality with the Kolmogorov-Smirnov test. For normal data, differences between groups were tested by t test or 1-way analysis of variance. Leptin levels were log10 transformed before analysis. For nonnormal data, group differences were analyzed by the Mann-Whitney U test. Correlations between lipid abnormalities and HAART duration were assessed by Spearman coefficient. Regression analysis was used to look for associations between anthropometry and the type and duration of HAART treatment. Statistical analyses were performed using SPSS software (PC version 12.0; SPSS, Chicago, IL), and significance was defined as P G 0.05. Ethical approval was given by the Institute of Child Health and Great Ormond Street Hospital Research Ethics Committee. Details of the 98 HIV-infected children enrolled in the study are shown in Table 1. All had vertically acquired HIV-1 infection, and 85% were of sub-Saharan African origin. At enrollment, 59 children (60%) were receiving combination HAART. Of these, 23 (39%) were receiving stavudine (d4T) as part of a backbone NRTI regimen. Twenty-four (41%) also received a PI, including 7 (12%) who were receiving both d4T and PI. Thirty-nine children (40%) were not on any treatment at enrollment, including 7 who had been previously treated, but had stopped therapy at least 6 months before entry. Thirty-two children had never been treated with HAART. Clinical features of lipodystrophy were seen in 5 (5%) of 98 children. The CDC clinical and CD4 immunologic categories of the patients are summarized in Table 1. A higher proportion of patients with CDC stage C (AIDS) received PIs as part of their HAART. As far as anthropometric measurements are concerned, when the untreated group was compared with the reference sample, they were found to have a higher BMI, waist circumference, biceps, triceps, and subscapular skinfolds, but lower arm, thigh, and calf circumferences. Compared with the untreated group (Table 2), children receiving PIs had lower measurements for height, weight, arm, thigh, calf, and waist circumference and lower triceps, subscapular, and suprailiac skinfolds. Children receiving HAART without PIs had LETTERS TO THE EDITOR