7th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 13–16 November 2005, Dublin, Ireland

FOUR WEEKS OF INDINAVIR DOES NOT ALTER ADIPOGENIC TRANSCRIPTION FACTORS IN HEALTHY HIV-NEGATIVE SUBJECTS

SS Shankar, LN Bell, HO Steinberg and RV Considine
Indiana University School of Medicine, Indianapolis, IN, USA

Antiviral Therapy 2005; Supplement 3:L20 (abstract no. 27)

INTRODUCTION AND OBJECTIVES: HIV-infected patients on antiretroviral therapy have been reported to develop a lipodystrophy syndrome. Both HIV-1 protease inhibitors, as well as nucleoside analogue reverse transcriptase inhibitors have been implicated. However, it is unclear if this is a direct drug effect, or a result of an interaction between drug and the underlying HIV infection. In order to dissect out the direct role of drug alone in this process, we studied the in vivo effect of a single protease inhibitor, indinavir, on the key adipogenic transcription factors, C/EBP-α, SREBP1c and PPAR-γ.

METHODS: We obtained abdominal subcutaneous adipose tissue samples from seven HIV-negative subjects at baseline, and after 4 weeks of daily oral indinavir at 800mg three times a day. Adipocytes were obtained by collagenase digestion and total RNA isolated by standard methods. Expression of C/EBP-α, SREBP1c and PPAR-γ mRNA was quantitated by real-time reverse transcription, normalized to expression of β-actin, using the delta Ct method.

RESULTS: The subjects had a mean age of 36 ±3 years, with a mean BMI of 29.5 ±1.9 kg/m². There was no change in BMI or waist-to-hip ratio after 4 weeks of indinavir. Indinavir administration had no effect on expression of C/EBP-a (304.0 ±32.3 vs 359.2 ±43.4), SREBP1c (82.0 ±14.0 vs 104.9 ±34.0), or PPAR-γ (350.7 ±54.0 vs 351.0 ±48.8 relative units).

CONCLUSIONS: Four weeks of the protease inhibitor indinavir does not alter adipogenic transcription factors in healthy HIV-negative subjects. Our findings indicate that indinavir does not appear to have a direct role in the development of lipodystrophy, suggesting that the lipodystrophy is likely either due to an interaction between drug and disease, or attributable to antiretroviral agents other than indinavir.

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2005-11-13
27

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