3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 23-26 October 2001, Athens, Greece

Prospective, 48-week, intensive metabolic and body composition study of amprenavir-based therapy (COL30309)

Antiviral Therapy 2001; 6(Suppl. 4):11 (abstract no. 14)

MP Dubé¹, D Qian², HE Melançon², FR Sattler², D Goodwin³, C Martinez², V Williams³ and TA Buchanan^2
1Indiana University, Indianapolis, Ind., USA; ²University of Southern California, Los Angeles, Calif.,USA; and ³GlaxoSmithKline, Research Triangle Park, NC, USA

BACKGROUND: Amprenavir may lack some of the metabolic effects of other PIs.

OBJECTIVE: Characterize the effects of amprenavir-based antiretroviral therapy on metabolism and body composition.

METHODS: Fourteen stable, non-diabetic, PI-naïve adults (12 men, two women) with CD4 >100 were prospectively evaluated by OGTT, IVGTT, lipid measures, and DEXA over 48 weeks after starting amprenavir 1200 mg/abacavir 300 mg/lamivudine 150mg twice a day.

RESULTS: Mean age was 38 years. Median CD4 at entry was 264 cells/µl and HIV RNA 5.0 log₁₀ copies/ml; 79% were <400 copies/ml at week 48 (ITT missing=failure analysis). There was no significant change in fasting glucose, fasting insulin, or HOMAIR. Insulin sensitivity (Si) by the minimal model did not fall significantly by week 8 or week 24, but was decreased at week 48 (baseline 4.9±0.8 min^-1 per µU/ml•10⁴, week 48 3.0±0.4, P=0.04 by ANOVA). Six subjects experienced new or worsening glucose tolerance by week 24, but fasting hyperglycemia did not occur. At week 48 (n=l1), subjects gained 4.9±1.8 kg (P=0.03). DEXA scan at week 48 showed increased lean tissue (+1.5±0.8 kg, P=0.07), fat mass (+3.4±1.2kg, P=0.03), trunk fat (+2.2±0.7 kg, P=0.01) and limb fat (+1.2±0.6 kg, P=0.054). The trunk:limb fat ratio increased from 1.40±0.13 to 1.49±0.15 (P=0.005). Week 48 self-reported body image questionnaires showed either no changes or increases in the amountof fleshin the face and limbs. Total-body bone mineral content (BMC) increased from 2.38±0.14 to 2.42±0.14 kg at week 48 (P=0.02).

CONCLUSIONS: Amprenavir-based therapy did not cause short-term insulin resistance. An increase in BMC occurred, suggesting this regimen may not have deleterious effects on bone metabolism. Insulin resistance appeared late following weight gain, particularly trunk fat, but loss of limb fat or facial lipoatrophy did not occur. Unlike the short-term insulin resistance reported with indinavir, these late changes appear to be related to increased adiposity rather than a direct drug effect.

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