8th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV San Francisco, California - September 24 - 26, 2006

EARLY CHANGES IN ADIPONECTIN AND LEPTIN LEVELS PREDICT CHANGES IN LIMB FAT MASS OVER 2 YEARS FOLLOWING INITIATION OF ANTIRETROVIRAL THERAPY

Antiviral Therapy 2006; 11:L12 (abstract no. 16)

A Calmy¹, D Carey², PW Mallon², H Wand², DA Cooper^1,2, M Law² and A Carr^1
1St Vincent’s Hospital, Sydney, NSW, Australia; ²National Centre in HIV Epidemiology and Clinical Research, University of New South Wales Sydney, NSW, Australia

BACKGROUND: Lipodystrophy (LD) has been associated with stavudine therapy and older age, but no biological marker has been found to predict the evolution of LD in patients receiving antiretroviral therapy (ART). We investigated whether metabolic markers could predict long term LD development.

METHODS: Using stored samples collected at baseline, weeks 12, 24 and 48 in two prospective studies of adults initiating combination ART, serial measurements of plasma adipokines, cytokines, and lipid, glycaemic and acid-base parameters related to fat mass and LD were performed. The association between plasma markers and subsequent development of lipoatrophy (change in limb fat mass between weeks 24 and 96 by DEXA) and lipohypertrophy (visceral fat gain [VAT] by abdominal CT to week 48) was investigated. Data were analysed using non parametric methods and Spearman’s coefficient used for correlations.

RESULTS: 54 HIV-infected, treatment-naïve adults were studied: 53 were males, median age 39 (IQR 34–48) years, body mass index (BMI) 22.6 (IQR 20–24.8) kg/m², and median CD4+ count 208 (IQR 102–320) cells/mm³. Most common nucleosides analogues were ddI and d4T, 34 (62%) were on a protease inhibitor containing regimen. Baseline BMI (r=-0.45; P=0.005) and leg fat (r=-0.53; P=0.0005) predicted changes in limb fat mass between week 24 and 96. Negative correlations between change in limb fat mass between weeks 24 and 96 and changes in leptin levels at baseline, week 12 and week 24, were consistently found (r=-0.34, P=0.03; r=-0.35, P=0.05; r=-0.44, P=0.005 respectively). Adiponectin change at week 48 was also significantly associated with change in limb fat mass between week 24 and 96 (r=0.61, P=0.0001). Changes to week 48 in lipids, insulin, lactate, TNF-α and HIV RNA were not predictive of limb fat change between weeks 24 and 96. Baseline TNF-α levels and changes between baseline and weeks 12, 24 and 48 were strong predictors of VAT change over 48 weeks (r=-0.53, P=0.0002, r=-0.4, P=0.009, r=-0.38, P=0.008, r=-0.36, P=0.02).

CONCLUSIONS: In ART-naïve individuals, early changes in adiponectin and leptin concentrations might assist in predicting long-term loss of limb fat. Both baseline BMI and leg fat mass were strong predictors of limb fat loss after 2 years of ART.

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2006-09-24
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