title: Lipodystrophy defined by a clinical score in HIV-infected men on highly active antiretroviral therapy: correlation between dyslipidaemia and steroid hormone alterations.
abstract: BACKGROUND
  A syndrome of lipodystrophy, associated with hypertriglyceridaemia, hypercholesterolaemia, hyperinsulinaemia and peripheral insulin resistance has been reported in protease inhibitor (PI)-treated HIV-infected patients. Because lipid metabolism, fat mass distribution and insulin resistance are partly regulated by steroid hormones, we questioned whether lipodystrophy is related to hormonal perturbations.
  
  
  OBJECTIVE
  To evaluate serum lipid and steroid hormone concentrations in HIV-positive men on highly active antiretroviral therapy (HAART) in order to determine whether dyslipidaemia, peripheral loss of fatty tissue and central fat accumulation are related to steroid hormone modifications.
  
  
  METHODS
  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 and their subclasses, apolipoproteins and steroid hormones, including cortisol, dehydroepiandrosterone (DHEA), DHEA sulphate, androstenedione, testosterone 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 atherogenic ratios of cholesterol:HDL cholesterol, LDL cholesterol:HDL cholesterol 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 significantly 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 SCSL was positively correlated with dyslipidaemia and the cortisol:DHEA ratio.
  
  
  CONCLUSIONS
  This study demonstrates an association between the cortisol:DHEA ratio, lipid alterations and lipodystrophy. This syndrome might result from an imbalance between peripheral lipolysis and lipogenesis, both regulated by cortisol and DHEA.
authors.affiliation: URA CNRS 1930, Département SIDA et Retrovirus, Institut Pasteur, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Christeff
authors.forename: J C
authors.initials: JC
authors.lastname: Melchior
authors.forename: P
authors.initials: P
authors.lastname: de Truchis
authors.forename: C
authors.initials: C
authors.lastname: Perronne
authors.forename: E A
authors.initials: EA
authors.lastname: Nunez
authors.forename: M L
authors.initials: ML
authors.lastname: Gougeon
mesh_terms: D000328:Adult; D000728:Androgens / Q000097:blood*; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D006949:Hyperlipidemias / Q000150:complications / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008060:Lipodystrophy / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged
chemical_list: D000728:Androgens; D019380:Anti-HIV Agents; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D006854:Hydrocortisone