Lipodystrophy defined by a clinical score in HIV-infected men on highly active antiretroviral therapy: correlation between dyslipidaemia and steroid hormone alterations

Background: A syndrome of lipodystrophy, associated with hypertriglyceridae mia, hypercholesterolaemia, hyperinsulinaemia and peripheral insulin resist ance has been reported in protease inhibitor (PI)-treated HIV-infected pati ents. Because lipid metabolism, fat mass distribution and insulin resistanc e are partly regulated by steroid hormones, we questioned whether lipodystr ophy is related to hormonal perturbations. Objective: To evaluate serum lipid and steroid hormone concentrations in HI V-positive men on highly active antiretroviral therapy (HAART) in order to determine whether dyslipidaemia, peripheral loss of fatty tissue and centra l fat accumulation are related to steroid hormone modifications. Design: A cross-sectional study. Methods: Thirty-seven HIV-1-positive men on HAART, 23 of whom had symptoms of lipodystrophy, according to a subjective clinical score of lipodystrophy (SCSL), were tested. Serum concentrations of cholesterol, triglycerides an d their subclasses, apolipoproteins and steroid hormones, including cortiso l, dehydroepiandrosterone (DHEA), DHEA sulphate, androstenedione, testoster one and dihydrotestosterone were measured. Results: Serum cholesterol, very low density lipoprotein (VLDL) cholesterol , triglycerides, VLDL triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL) triglycerides, apolipoprotein B (ApoB) and ather ogenic ratios of cholesterol : HDL cholesterol, LDL cholesterol : HDL chole sterol and ApoB : apolipoprotein A1 (ApoA1) were significantly increased in lipodystrophy-positive compared with lipodystrophy-negative men. The serum cortisol level was similar in lipodystrophy-positive versus lipodystrophy- negative men, but was elevated compared with controls. Serum DHEA was signi ficantly lower in lipodystrophy-positive versus lipodystrophy-negative men and, consequently, the cortisol : DHEA ratio was increased in lipodystrophy -positive patients. A positive correlation was found between the cortisol: DHEA ratio and increased levels of atherogenic lipids. In addition, the SCS L was positively correlated with dyslipidaemia and the cortisol : DHEA rati o. Conclusion: This study demonstrates an association between the cortisol : D HEA ratio, lipid alterations and lipodystrophy. This syndrome might result from an imbalance between peripheral lipolysis and lipogenesis, both regula ted by cortisol and DHEA. (C) 1999 Lippincott Williams & Wilkins.