660   The Clinical Evolution of Lipodystrophy Syndrome Is Closely Related to Cortisol:DHEA Ratio and Serum IFN-α;. N. Christeff¹, P. Truchis², J.-C. Melchior², and M. L. Gougeon¹.

¹Inst. Pasteur, Paris and²Hosp. Raymond Poincaré, Garches, France.

Background:- We have previously shown in a cross-sectional study that lipid alterations associated with the lipodystrophy syndrome (LD) in HIV-1-infected men on combined therapy are correlated with decreased DHEA, increased cortisol/DHEA ratio, and increased serum IFNα;levels (Christeff et al., AIDS13:2251, 1999). In this study, we asked whether clinical evolution of LD is associated with changes in these parameters.

Methods:31 HIV-1-positive men on combined therapy, 20 of them showing LD defined by computed tomography scan, were tested for a 14- to 24-month interval. LD patients were subdivided according to their clinical evolution as follows: aggravated (n = 5); unchanged (n = 9), or improved (n = 6). Serum lipids (cholesterol, triglycerides, their subclasses, and apolipoproteins), cortisol, DHEA and IFN-α;were measured and compared to baseline values of the follow-up.

Results:We show that : 1) LD aggravation is associated with an increase in serum lipids, a decrease in DHEA, a dramatic increase in cortisol/DHEA ratio (+55%, p < 0.04) and persistent high levels of IFN-α;; 2) the absence of LD evolution is associated with persistent elevated lipids, a slight increase in DHEA, a significant decrease in cortisol/DHEA ratio (-25%, p < 0.03), and a decrease in IFN-α;; 3) LD improvement is associate with to normalization of serum lipids, a dramatic increase in DHEA (+90%, p < 0.04) leading to normalization of the cortisol/DHEA ratio, and normalization of IFN-α;levels. The follow-up of LD-negative men (n = 11) revealed that those who remained LD-negative (n = 9) showed normal lipids, elevated cortisol, highly elevated DHEA, leading to a normal cortisol/DHEA ratio, and normal levels of IFN-α;. The two patients who developed LD showed an increase in lipids levels, a decrease in DHEA concentration, an increase in cortisol/DHEA ratio and increased IFN-α;levels.

Conclusions:This study demonstrates that clinical evolution of LD and lipid alterations in HIV-1-positive men on combined therapies are both closely related to changes in cortisol/DHEA ratio and IFN-α;concentrations.