Longitudinal evolution of HIV-1-associated lipodystrophy is correlated to serum cortisol:DHEA ratio and IFN-α

Authors


  • Molecular Medicine Department, URA CNRS 1930, Institut Pasteur (N. Christeff, M-L. Gougeon); Service des Maladies Infectieuses et Tropicales, Hôpital Raymond Poincaré, Garches, (P. de Truchis, J-C. Melchior, C. Perronne); Laboratoire de Biochimie B, CHU Bichat Claude Bernard (N. Christeff), Paris Cedex, France.

Marie-Lise Gougeon, Molecular Medicine Department, URA CNRS 1930, Institut Pasteur, Paris Cedex, France. Tel.: +33–45–68–89–07; fax: +33–45–68–89–09; e-mail: mlgougeo@pasteur.fr

Abstract

Background We have previously shown that lipid alterations in HIV-1-associated lipodystrophy (LD) are correlated with decreased serum dehydroepiandosterone (DHEA) and increased cortisol:DHEA ratio and IFN-α levels.

Objective To evaluate in a longitudinal study whether steroid and cytokine modifications are associated with the evolution of physical changes and lipid alterations associated with LD.

Methods Thirty-four HIV-1-positive men were followed during 32·5 ± 4·0 months and tested at four time-points. The patients were subdivided into five groups according to physical changes and anthropometric measurements: LD-negative, initially LD-negative becoming LD-positive, LD-positive unchanged, aggravated or improved. Serum lipids, apolipoproteins, adrenal steroids and cytokines were measured and compared with baseline values.

Results (1) LD aggravation is associated with persistent elevated lipids, a decrease in serum DHEA, an increase in cortisol:DHEA ratio and persistent high levels of IFN-α. (2) LD improvement is associated with normalization of serum lipids, an increase in serum DHEA leading to normalization in cortisol:DHEA ratio, and normalization of IFN-α levels. (3) In LD-positive men evolution of VLDL cholesterol is negatively correlated with DHEA (r = −0·56, P < 0·01) and positively with cortisol:DHEA ratio (r = 0·62, P < 0·004) and with IFN-α (r = 0·57, P < 0·01). (4) The switch to LD is associated with a decrease in serum DHEA. (5) Patients who remained LD-negative maintained normal lipids, elevated cortisol and DHEA, and normal cortisol:DHEA ratio and normal levels of IFN-α.

Conclusions This study indicates that cortisol:DHEA ratio and serum IFN-α levels are closely associated with clinical evolution and atherogenic lipid alterations in LD.

Ancillary