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The protease inhibitor combination lopinavir/ritonavir does not decrease insulin secretion in healthy,

Vivian Y Pao1, Grace A Lee, Steven Taylor

  • 1Department of Medicine, University of California, CA, USA.

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Lopinavir/ritonavir did not affect insulin secretion in HIV-negative individuals. However, this protease inhibitor combination significantly worsened lipid profiles, suggesting HIV-related factors may influence drug effects in patients.

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Area of Science:

  • Metabolic effects of antiretroviral therapy
  • Pharmacology of HIV protease inhibitors
  • Endocrinology and lipid metabolism

Background:

  • HIV protease inhibitors (PIs) are known to disrupt glucose and lipid metabolism.
  • Emerging evidence suggests PIs may impair insulin secretion in individuals with HIV.
  • This study investigates the impact of a specific PI combination on metabolic parameters in HIV-negative subjects.

Purpose of the Study:

  • To evaluate the effects of lopinavir/ritonavir on insulin secretion, insulin sensitivity, and lipid metabolism.
  • To determine if the metabolic disturbances associated with PIs are a direct drug effect or related to HIV infection.
  • To assess changes in glucose homeostasis and body composition.

Main Methods:

  • Eight HIV-seronegative men received lopinavir 400 mg/ritonavir 100 mg twice daily for 4 weeks.
  • Fasting glucose, insulin, lipids, lipoproteins, and oral glucose tolerance tests were performed.
  • Hyperglycemic clamp studies assessed insulin secretion and disposal; dual-energy X-ray absorptiometry measured body composition.

Main Results:

  • No significant changes were observed in first-phase insulin secretion, fasting glucose/insulin levels, oral glucose tolerance, or insulin-mediated glucose disposal.
  • Significant increases in fasting triglycerides, total cholesterol, and apo B-100 levels were noted.
  • High-density lipoprotein cholesterol levels decreased significantly; body composition remained unchanged.

Conclusions:

  • Lopinavir/ritonavir administration in healthy HIV-negative individuals did not impair first-phase insulin secretion.
  • The drug combination led to adverse changes in lipid profiles (increased triglycerides, decreased HDL cholesterol).
  • Observed insulin secretion impairments in HIV-infected patients may be linked to HIV-related factors rather than a direct drug effect.