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

ABSENCE OF INSULIN RESISTANCE THROUGH WEEK 24 WITH ATAZANAVIR ONCE-DAILY AND EFAVIRENZ ONCE-DAILY EACH WITH FIXED-DOSE ZIDOVUDINE PLUS LAMIVUDINE

Antiviral Therapy 2002; 7:L26 (abstract 36)

M Sension¹, A Thiry² and M Giordano² for the AI424-034 International Study Team
¹North Broward Hospital District, Comprehensive Care Ctr, Ft. Lauderdale, Fla., USA; ²Bristol-Myers Squibb Company, Wallingford, Conn., USA

BACKGROUND: Therapy with current protease inhibitors (PIs) is complicated by hyperglycaemia, insulin resistance and hyperlipidaemia. Atazanavir is a potent, safe, once-daily PI with a distinct resistance profile in vitro that is associated with lipid parameters superior to marketed PIs. In vitro atazanavir does not inhibit insulin-stimulated glucose transport through GLUT-4. Efavirenz, a standard of care for treatment of HIV, is not associated with insulin resistance.

OBJECTIVE/AIM: Compare fasting glucose, insulin and C-peptide as well as total cholesterol (TC) and HDL-C in atazanavir- and efavirenz-treated subjects as part of an ongoing, double-blind, multinational, randomized trial.

METHODS: 805 antiretroviral-naïve subjects treated with atazanavir 400 mg (n=404) once-daily or efavirenz 600 mg (n=401) once-daily, each in combination with fixed-dose zidovudine + lamivudine had measurements of glucose, insulin, C-peptide, TC and HDLC at baseline and multiple weeks on therapy.

RESULTS: Mean values ±SE at baseline vs 24 weeks were: glucose (mg/dl), 90 ±0.6 vs 92 ±0.8, atazanavir, and 90 ±1.1 vs 94 ±1.0, efavirenz; insulin (µU/ml), 11.3 ±0.76 vs 12.0 ±0.6, atazanavir, and 9.9 ±0.43 vs 10.0 ±0.42, efavirenz; C-peptide (ng/ml), 2.2 ±0.08 vs 2.4 ±0.07, atazanavir, and 2.1 ±0.06 vs 2.2 ±0.06, efavirenz; TC (mg/dl), 164 ±1.8 vs 166 ±1.9, atazanavir, and 162 ±1.8 vs 194 ±2.4, efavirenz; HDLC (mg/dl), 39 ±0.6 vs 42 ±0.7, atazanavir, and 38 ±0.6 vs 46 ±0.8, efavirenz. Mean changes from baseline at 24 weeks were +1% and +20% (TC) and +9% and +21% (HDL-C) for the atazanavir and efavirenz groups, respectively. At week 24, the proportions of subjects with a favorable TC/HDL-C ratio (<5) were 76% (atazanavir) vs 68% (efavirenz).

CONCLUSIONS: Atazanavir once-daily as part of a highly active antiretroviral regimen, like efavirenz, is not associated with the development of insulin resistance as assessed by fasting insulin, C-peptide and glucose concentrations. This is unique among PIs and consistent with atazanavir’s effect on GLUT-4 in vitro. In addition, atazanavir was not associated with increases in TC through 24 weeks. Most patients on both the atazanavir and efavirenz regimens had favorable TC/HDL-C ratios.

Presenting author: M Sension

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