2nd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 13-15 September 2000, Toronto, Canada

PROSPECTIVE STUDY OF THE EFFECTS OF AMPRENAVIR-BASED THERAPY ON GLUCOSE AND LIPID METABOLISM IN HIV-INFECTED PATIENTS

Antiviral Therapy 2000; 5(Suppl. 5):26 (abstract no. P4)

MP Dubé¹, D Qian^2,3, H Edmondson-Melanç;on⁴, FR Sattler^3,4, D Goodwin⁵, C Martinez³, V Williams⁵, D Johnson⁴ and TA Buchanan^3,6
1Medicine and Infectious Diseases, Indiana University, Indianapolis, Ind.; ⁵Glaxo Wellcome, Research Triangle Park, N.C.; ²Preventive Medicine; ³GCRC; ⁴Infectious Diseases; and ⁶Endocrinology,USC and the LA County-USC Medical Center, Los Angeles, Calif., USA

BACKGROUND: Insulin resistance and hyperlipidemia can complicate treatment with protease inhibitors (PIs). Animal data suggest that amprenavir has metabolic effects that differ from other PIs.

DESIGN: Stable, non-diabetic, HIV-infected, PI-naïve adults with CD4 >100 cells/mm³ underwent oral and IV glucose tolerance tests (GTT) at entry, then 2, 8, 24 and 48 weeks after starting amprenavir 1200 mg twice daily, abacavir 300 mg twice daily and lamivudine 150 mg twice daily. Fifteen subjects have been enrolled; we report on the first 10 to reach week 8 of study.

RESULTS: Nine men and one woman (mean age, 36 years) were studied. Mean CD4 at entry was 301 cells/mm³ and mean HIV RNA was 4.76 log₁₀ copies/ml; all experienced a virologic response to <50 copies/ml or ≥2log₁₀ decrease at week 8. There was no change in (±SE) fasting glucose (96±3 mg/dl at baseline, 94±3 week 8), insulin (9.5±1.6 µU/ml, 12.7±4.9), and HOMA insulin resistance (2.2±0.4, 3.0±1.2, all P>0.77). Insulin sensitivity by minimal model analysis of the IV GTI also did not change (baseline, 5.1±1.1 min^-1 per µU/ml x10⁴; week 8, 4.6±1.0; P=0.92) nor did insulin secretion measured by acute insulin response to IV glucose (AIR_G baseline 756±162 µU/ml.min; week 8, 870±170; P=0.25). Total fasting cholesterol rose from 163±17 mg/dl to 213±20 (P<0.01) at week 8, directly measured LDL-C rose from 77±5 to 100±6 (P<0.01), triglycerides rose from 103±16 to 144±19 (P=0.08), and HDL-C rose from 30±4 to 33±3 (P=0.32). Food diaries showed no increase in intake of total calories or fat at 8 weeks compared to baseline.

CONCLUSIONS: Over the first 8 weeks of this study, amprenavir-based therapy did not measurably affect glucose metabolism, but was associated with significant increases in cholesterol. In contrast, our previous study using the same measures (1st IWADRHL, 1999) showed increased fasting glucose and reduced insulin sensitivity during 8 weeks of indinavir-based therapy, without significant changes in lipids. Although they can co-exist, PI-associated glucose and lipid dysregulation may not necessarily result from the same pathogenic mechanism.

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P4

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