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

METABOLIC EFFECTS OF INDINAVIR IN HEALTHY HIV-SERONEGATIVE SUBJECTS

Antiviral Therapy 2000; 5(Suppl. 5):8 (abstract no. O10)

M Noor¹, J Lo², K Mulligan², R Halvorsen², JM Schwarz^2,3, M Schambelan² and C Grunfeld^1
1Veterans Affairs Medical Center and University of California, San Francisco; ²San Francisco General Hospital and University of California, San Francisco; and ³University of California, Berkeley, Calif., USA

BACKGROUND: It is unclear whether adverse metabolic effects associated with protease inhibitors are drug-related, reflect changes in body composition or involve an interaction with the host response to HIV infection.

OBJECTIVES: To distinguish between direct metabolic effects of indinavir and those that may be related to HIV infection and changes in body composition.

DESIGN: Open-label study of the effects of indinavir 800 mg three times daily in 10 HIV-seronegative healthy volunteer men. We studied carbohydrate metabolism (fasting glucose and insulin, oral glucose tolerance test, hyperinsulinemic euglycemic clamp), fasting lipid profile and body composition (DEXA, BIA, sliced CT of abdomen) at baseline and again after 4 weeks on indinavir.

RESULTS: Subjects ranged in age from 30 to 65 years (mean±SEM 42.1±3.9 years), 4/10 were non-white. After 4 weeks on indinavir there was no significant change in weight, BMI, percentage total or regional body fat by DEXA, or visceral and subcutaneous adipose tissues by CT. Fasting plasma glucose (88.3±1.9 versus 92.7±3.0 mg/dl, P=0.05) and insulin (8.6±1.7 versus 11.7±1.7, P<0.05), I/G ratio (12.6±1.7 versus 15.9±1.9 pmol/mmol, P<0.05) and HOMA insulin resistance index (1.9±0.3 versus 2.8±0.5, P<0.05) all increased. During OGTT, 2 h glucose (91.4±7.1 versus 117.3±11.2 mg/dl, P<0.05) and insulin level (31.1±6.8 versus 54.4±l5.3, IU/l, P=0.05) also increased. A trend towards an increase in overall area-under-curve for both glucose and insulin was also observed. Insulin-mediated glucose disposal rate (Mil) during euglycemic hyperinsulinemic clamp decreased significantly (10.4±1.4 versus 8.6±1.2 mg/kg.min/IU/l, 95% CI 0.6-3.0, P<0.01). There was no significant change in total, LDL and HDL cholesterols, triglycerides or free fatty acids.

CONCLUSIONS: Treatment with indinavir in the absence of HIV infection or changes in body composition causes insulin resistance with little effect on lipids and lipoproteins.

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