1st International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 26–28 June 1999 - San Diego, CA, USA

REVERSIBILITY OF PERIPHERAL FAT WASTING (LIPOATROPHY) ON STOPPING STAVUDINE THERAPY

Antiviral Therapy 1999; 4(Suppl. 2):45 (abstract no. 24)

T Saint-Marc and JL Touraine
Transplantation and Clinical Immunology Unit, Hôpital E Herriot, Lyon, France

BACKGROUND: A syndrome of peripheral fat wasting (facial fat pads, arms and legs), insulin resistance and hyperlipidaemia has been identified in patients treated with PI-containing regimens. However, several reports suggest that stavudine may be associated with limb and facial fat wasting.

OBJECTIVES: To assess the effects of stavudine therapy discontinuation on metabolic and clinical abnormalities in HIV-1 infected patients with peripheral fat wasting but without central adiposity.

METHODS: Body composition (BIA), regional fat distribution (abdominal and mid-thigh CT scan), fasting lipids, insulin, C-peptide and pyruvate levels and glucose tolerance were measured at baseline and after 6 months of stavudine discontinuation in 14 patients on stable NRTI therapy (NRTI group), and in 15 patients undergoing PI-containing combination therapy, and compared to 15 and 16 HIV-infected patients on NRTI and PI therapy, respectively, exhibiting no change in body fat distribution.

RESULTS: After 6 months of discontinuation mean plasma triglyceride and pyruvate levels dropped by 46% and 37.5% and by 36% and 20.8% in the NRTI and PI groups, respectively. No significant differences were observed among the two groups with regard to cholesterol, glucose and insulin measurements. A significant (P<0.05) increase in body fat was observed in both groups. In particular, abdominal and midthigh subcutaneous fat area increased by 41 % and 40.7% in the NRTI group (P<0.01) and 27% and 40.7% in the PI group (P<0.01). All improvements were incomplete when compared with controls. Higher fasting triglyceride, C-peptide and pyruvate levels distinguished patients with fat wasting from those without, particularly in the PI group. Of note, although the drug was discontinued fat loss continued to worsen in some patients during the first two months.

CONCLUSIONS: These non-randomized data suggest that ceasing stavudine therapy for 6 months resulted in improvements in metabolic and body fat abnormalities induced by stavudine. The reversibility of the symptoms further support the potential role of stavudine in the pathogenesis of a peripheral fat wasting syndrome.

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