Lipodystrophy in patients with HIV-1 infection: effect of stopping protease inhibitors on TNF-alpha and TNF-receptor levels, and on metabolic parameters.
OBJECTIVE
To evaluate the effects of stopping treatment with protease inhibitors (PIs) on tumour necrosis factor (TNF)-alpha and TNF-receptor levels, and on the metabolic and morphological abnormalities seen in patients with lipodystrophy.


METHODS
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-alpha and TNF-receptor levels, insulin resistance parameters, lipid and hormonal profiles, body composition and fat distribution were measured in all subjects.


RESULTS
TNF-alpha, 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.


CONCLUSIONS
Our results show that TNF-alpha 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.
Maher
Bridget
B
Department of Pharmacology, University of Liverpool, Liverpool, UK.
Lloyd
Judy
J
Wilkins
Edmund G L
EG
Fraser
William D
WD
Back
David
D
Park
B Kevin
BK
Pirmohamed
Munir
M
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001823:Body Composition; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D019380:Anti-HIV Agents; D008055:Lipids; D011480:Protease Inhibitors; D018124:Receptors, Tumor Necrosis Factor; D018894:Reverse Transcriptase Inhibitors; D014409:Tumor Necrosis Factor-alpha