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. Address correspondence and reprint requests to Michael P. Dubé, Wishard Memorial Hospital, 1001 W. Tenth Street, Suite OPW-430, Indianapolis, IN 46202 U.S.A.; e-mail [email protected] Manuscript received November 2, 2000; accepted February 23, 2001. © 2001 Lippincott Williams & Wilkins, Inc.