Absence of hypersensitivity to glucocorticoids in antiretroviral-associated lipodystrophy

The lipodystrophy syndrome, which is associated with the use of antiretroviral drugs in some human immunodeficiency virus (HIV)-infected individuals, bears a striking similarity to the fat redistribution observed in Cushing's disease. Although urinary free cortisol excretion and glucocorticoid receptor binding affinity are not elevated in subjects with lipodystrophy, glucocorticoid action at the cellular level has not been examined in affected individuals. The objective of this study was to determine whether tissue sensitivity to glucocorticoids is increased in subjects with lipodystrophy taking protease inhibitors.

Subjects included 11 HIV-infected men on protease inhibitor therapy with lipodystrophy and 10 control HIV-infected men not on protease inhibitor therapy and without lipodystrophy. Trunk to extremity fat ratio was measured by DXA. Dexamethasone suppression of peripheral blood mononuclear cell proliferation was measured as an index of tissue sensitivity to glucocorticoid action.

Compared with the control group, subjects with lipodystrophy had a significant elevation of the trunk to extremity fat ratio [median (interquartile range): 2.9 (1.3) vs. 1.6 (1.2); p < 0.05]. The concentration of dexamethasone resulting in 50% maximal suppression of proliferation was 11.7 nM (9.3 nM) in subjects with lipodystrophy and 19.6 nM (9.7 nM) in control subjects (p = not significant), and the percentage minimal proliferation was 4% (12%) and 17% (18%) in the two groups, respectively (p = not significant).

Despite the Cushingoid appearance of affected individuals, these data suggest that body fat redistribution in antiretroviral-associated lipodystrophy does not arise through an increase in postreceptor glucocorticoid signaling.