4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 22-25 September 2002, San Diego, CA, USA

BOTH STAVUDINE AND ZIDOVUDINE-BASED THERAPY IS ASSOCIATED WITH GLUTEAL SUBCUTANEOUS ADIPOCYTE DEPLETION

Antiviral Therapy 2002; 7:L22 (abstract 30)

J Morlese¹, N Qazi¹, C Orkin¹, D Datta¹, R Abbas¹, B Gazzard¹, N Francis² and G Moyle^1
1St Stephen’s Centre, Chelsea and Westminster Hospital; ²Histopathology Department, Charing Cross Hospital, Imperial College, London

INTRODUCTION: Lipoatrophy is a stigmaitising dysmorphology observed during antiretroviral therapy (ART). The aetiology of lipoatrophy is unclear. Nucleoside analogue (NA) treatment is associated with lipoatrophy but the relative contributions of each NA to lipoatrophy has not been determined.

AIMS: To determine which NA combinations are most associated with the presence of lipoatrophy on fat biopsy.

METHODS: HIV-1-infected protease inhibitor-naïve patients currently treated with their first ART for greater than 1 year were studied. All the patients had a subcutaneous fat biopsy taken from the left buttock to determine the extent of fat loss using light microscopy and mitochondrial depletion using electron microscopy. The patients also had fasting plasma lipids, an oral glucose tolerance test, kidney and liver function tests, CD4 and HIV-1 RNA load and a full endocrine profile performed. HIV-negative individuals acted as controls. Histology was performed blinded to therapy/status.

RESULTS: Forty-two male patients and eight controls were included. Groups were well matched for age, CD4 and viral load and therapy duration. One out of 10 patients treated with stavudine/didanosine and four out of 10 treated with stavudine/lamivudine had evidence of gluteal lipoatrophy compared with one out of three treated with zidovudine/didanosine, five out of nine treated with zidovudine/lamivudine and one out of three treated with zidovudine/zalcitabine. None of the eight HIV-1-uninfected male control patients had evidence of gluteal lipoatrophy. The mean ±SE fasting total cholesterol, triglycerides, glucose and lactate were 5.3 ±0.7, 1.8 ±0.7, 5.2 ±0.6 and 1.4 ±0.8 in the stavudine/ didanosine group; 5.3 ±1.5, 1.9 ±0.6, 5.2 ±1.0 and 1.2 ±0.3 in the stavudine/lamivudine group; 4.5 ±0.6, 0.8 ±0.1, 5.3 ±0.6 and 1.5 ±0.6 in the zidovudine/didanosine group; 6.4 ±2.1, 3.1 ±3.7, 4.9 ±0.8, 1.3 ±0.7 in the zidovudine/lamivudine group; 4.0 ±0.2, 1.3 ±0.5, 6.1 ±0.5, 1.2 ±0.1 in the zidovudine/zalcitabine group and 5.5 ±0.6, 1.1 ±0.6, 5.0 ±0.3, 1.0 ±0.2 in the control patients, respectively.

CONCLUSIONS: Both stavudine and zidovudine-based ART is associated with significant gluteal subcutaneous adipocyte depletion. Lamivudine was associated with somewhat more adipocyte depletion than didanosine or zalcitabine. Nucleoside analogue choice may not play an important role in lipoatrophy development.

Presenting author: G Moyle

2002-09-22
30

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