The Effect of Nevirapine in Combination With Nelfinavir in Heavily Pretreated HIV-1–Infected Patients

Abstract

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/μl 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 μU/ml × 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 μU/ml × 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 μU/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.