Lipodystrophy in Patients with HIV-1 Infection: Effect of Stopping Protease Inhibitors on Tnf-α and Tnf-Receptor Levels,and on Metabolic Parameters

Abstract

Objective

To evaluate the effects of stopping treatment with protease inhibitors (PIs) on tumour necrosis factor (TNF)-α and TNF-receptor levels, and on the metabolic and morphological abnormalities seen in patients with lipodystrophy.

Design

Longitudinal study.

Methods

Ten HIV-positive patients with lipodystrophy (LD) were studied whilst on PIs (LD1) and 3 months after stopping PIs (LD2) together with 10 HIV-positive subjects on PIs without LD (controls). TNF-α and TNF-receptor levels, insulin resistance parameters, lipid and hormonal profiles, body composition and fat distribution were measured in all subjects.

Results

TNF-α, TNF-receptor I (-RI) and TNF-RII levels were significantly lower in controls (P=0.02) than in subjects with LD, and there was a significant decrease in TNF-RI and TNF-RII levels (P=0.01 and 0.03, respectively) on stopping PIs. Insulin levels and the homeostasis model assessment for insulin resistance (HOMA-IR) index were significantly higher in LD1 subjects (P=0.02) than in controls but did not alter when PIs were stopped. Bioelectrical impedance analysis showed a significant decrease on stopping PIs but CT scans showed no significant difference in fat distribution. Apart from high-density lipoprotein, there was no change in lipid parameters on stopping PIs. There was no difference in the level of testosterone, sex hormone binding globulin and cortisol between the three groups.

Conclusion

Our results show that TNF-α activity in patients with LD is modulated by PIs. This was not accompanied by significant changes in body habitus or insulin resistance, although this may have been a consequence of the short follow-up in this study.