Greater lipodystrophy risk in older US children with low viral load
Mark Mascolini, for NATAP.org
Older age, perinatal HIV infection, antiretroviral therapy, and an on-treatment viral load below 400 copies independently raised the risk of lipodystrophy in a LEGACY cohort study involving 1490 US children, adolescents, and young adults. 
Girls were twice more likely than boys to be diagnosed with lipodystrophy.
Use of nucleosides, usually blamed for lipodystrophy, did not independently boost the risk of body fat abnormalities in this cohort, although treatment with a protease inhibitor (PI) or a nonnucleoside (NNRTI) did. The overall lipodystrophy prevalence stood at only 9% in the LEGACY cohort, much lower than rates in some other studies of antiretroviral-treated children [2-4], but similar to prevalence in another large US study. 
The LEGACY cohort includes 1490 people between 2 and 24 years old, 140 (9%) of whom had a diagnosis or symptoms of lipodystrophy in the cross-sectional part of this study. The investigators looked more closely at 575 youths for whom they had a complete treatment history from 2001 through 2006. Eighty-five youngsters and young adults in this longitudinally studied group (15%) had lipodystrophy, a rate still well below those found in three non-US studies. [2-4]
Multivariate analysis in the 1490-person group isolated seven factors that independently hoisted the risk of lipodystrophy at the following odds ratios (OR) and 95% confidence intervals (CI):
- Age 11 years or older: OR 1.1, 95% CI 1.0 to 1.1, P = 0.0068
- Perinatal HIV infection: OR 6.5, 95% CI 2.4 to 17.4, P = 0.0002
- Female gender: OR 2.2, 95% CI 1.5 to 3.2, P = 0.0002
- Viral load below 400 copies: OR 2.3, 95% CI 1.5 to 3.4, P < 0.0001
- Any NNRTI use: OR 2.1, 95% CI 1.3 to 3.3, P = 0.0012
- Any PI use: OR 1.9, 95% CI 1.2 to 2.9, P = 0.0047
- Serum triglycerides at or above 500 mg/dL: OR 3.2, 95% CI 2.1 to 4.7, P < 0.0001
Four of these factors (age, perinatal infection, low viral load, high triglycerides) suggest that longer HIV infection and longer antiretroviral treatment boosted the risk of lipodystrophy in this cohort. It is curious that nucleoside use did not make lipodystrophy more likely since the vast majority of cohort members taking a PI or an NNRTI would also be taking a nucleoside. Other factors that did not significantly affect lipodystrophy risk in the multivariate analysis were race/ethnicity, total cholesterol at or above 200 mg/dL, and CD4% above 25.
In the 575-person subgroup analysis, youngsters with lipodystrophy started potent combination therapy at a significantly earlier average age than those without lipodystrophy (8.2 versus 10.9 years, P = 0.007). Cohort members with lipodystrophy were significantly younger than those without lipodystrophy when they started any PI, ritonavir, any nucleoside, stavudine (d4T), or any NNRTI.
Three recently published pediatric cohort studies found higher rates of lipodystrophy in Europe (26% in 477 children) , Thailand (9% after 48 weeks of NNRTI therapy for 90 children, but 65% after 144 weeks) , and Romania (33% in 88 children) . But a longitudinal 1999-2004 study of 178 US children in the PACTS-HOPE Group charted a lipodystrophy rate of only 5.6%. 
- Paul ME, Frederick T, Siberry GK, et al. Risk factors associated with lipodystrophy in HIV-infected children and adolescents in the LEGACY cohort study, USA, 2006. 48th ICAAC, 25-28 October 2008. Washington. Abstract H-462.
- European Paediatric Lipodystrophy Group. Antiretroviral therapy, fat redistribution and hyperlipidaemia in HIV-infected children in Europe. AIDS. 2004;18:1443-1451.
- Aurpibul L, Puthanakit T, Lee B, et al. Lipodystrophy and metabolic changes in HIV-infected children on non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy. Antivir Ther. 2007;12:1247-1254.
- Ene L, Goetghebuer T, Hainaut M, et al. Prevalence of lipodystrophy in hIV-infected children: a cross-sectional study. Eur J Pediatr. 2007;166:13-21.
- Carter RJ, Wiener J, Abrams EJ, et al; Perinatal AIDS Collaborative Transmission Study-HIV Follow-up after Perinatal Exposure (PACTS-HOPE) Group. Dyslipidemia among perinatally HIV-infected children enrolled in the PACTS-HOPE cohort, 1999-2004: a longitudinal analysis. J Acquir Immune Defic Syndr. 2006;41:453-460.