Objective: To determine whether initiation of antiretroviral therapy that includes the protease inhibitor indinavir causes insulin resistance or abnormal B-cell function in study subjects with HIV infection.

Methods: Nonwasted, HIV-infected study subjects who did not have concurrent diabetes were prospectively evaluated by oral and intravenous glucose tolerance testing at baseline, at 2 weeks after starting indinavir monotherapy, and at another 6 weeks after initiating indinavir-based triple-therapy.

Results: Mean CD4 count at entry was 282 cells/[mu] l and median HIV RNA was 33,000 copies/ml; all experienced a virologic response. Fasting glucose increased from 83.2+/-3.7 mg/dl at baseline to 86.8+/-3.2 at week 2 and 91.7+/-3.5 at week 8 (p=. 003). Insulin sensitivity by minimal model analysis decreased by 30.5% over 8 weeks, from 3.83+/-0.63 min-1 per [mu] U/ml x 10-4 to 3.09+/-0.53 at week 2 and 2.66+/-0.35 at week 8 (p=. 01). Insulin secretion by the acute insulin response to intravenous glucose did not change (baseline 822+/-283 [mu] U/ml x min, week 8 880+/-289; p= 0.4), and the insulin response to oral glucose (30 minute insulin: glucose ratio) fell from 1.69+/-0.54 [mu] U/ml per mg/dl at baseline to 1.18+/-0.34 at week 8 (p=. 05).

Conclusion: During 8 weeks of indinavir-based therapy, fasting glucose increased and insulin sensitivity decreased, without a compensatory increase in insulin release. This combination of insulin resistance without augmented B-cell response may explain the hyperglycemia and other metabolic abnormalities seen in some protease inhibitortreated patients.