539   Assessment of Lipodystrophy in Patients Previously Exposed to AZT, ddI or ddC, but Naive for d4T and Protease Inhibitors (PI), and Randomized Between d4T/3TC/ Indinavir and AZT/3TC/Indinavir (NOVAVIR Trial).

V. Joly*, P. Flandre, V. Meiffredy, S. Hazebrouck, M. Harel, J. P. Aboulker, and P. Yeni.
ANRS, Paris, France.

Background:Our objective was to evaluate clinical lipodystrophy (body shape abnormalities) and metabolic abnormalities in HIV-1-infected patients (Pts) randomized to receive either AZT or d4T, in combination with a backbone regimen of 3TC and indinavir. NOVAVIR was a randomized multicenter trial comparing d4T/3TC/IDV and AZT/3TC/IDV in 170 Pts pretreated with AZT, ddI and/or ddC (>6 months) but naive for 3TC, d4T and PIs. Median duration of previous nucleoside therapy (Rx) was 19.3 months.

Methods:Intent-to-treat analysis did not show any significant difference in the antiviral efficacy or in the toxicity of the two regimens. At M30, clinical lipodystrophy was assessed by a physician through a standardized questionnaire evaluating peripheral fat depletion (facial, upper limb, lower limb or buttock atrophy, venomegaly) and central fat accumulation (increased abdominal wall thickness, neck, breast, or waist size, buffalo hump). Bicipital, tricipital, scapular, suprailiac and thigh skinfolds were measured. Fasting total cholesterol, triglycerides and glucose blood levels were determined.

Results:96 Pts were evaluated. Plasma HIV RNA was below 500 cps/ml in 82% of Pts. The incidence of lipoatrophy clinical signs was increased in the d4T arm versus the AZT arm, as followed: facial atrophy: 44% vs 29% of Pts, p = 0.006; lower limb atrophy: 50% vs 22% of Pts, p = 0.005; buttock atrophy: 48% vs 18% of Pts, p = 0.002; and venomegaly: 58% vs 22% of Pts, p = 0.004. The proportions of Pts with 0, 1 or>2 clinical signs of lipoatrophy were 27%, 29% and 44% in the d4T arm and 59%, 24% and 18% in the AZT arm, p = 0.003. The median thigh skinfold was significantly lower in the d4T arm (6.65 mm, IQR: 4.1—7.4) than in the AZT arm (8.80, IQR: 6—17). There was no significant difference in the incidence of clinical signs of central fat accumulation or in fasting triglycerides, total cholesterol and glucose blood levels at M30 between the 2 arms.

Conclusion:In this study, d4T increased the incidence of clinical lipoatrophy compared to AZT in Pts treated with a PI-containing regimen.