Variability in activity of hepatic CYP3A4 in patients infected with HIV

Abstract

Study objectives: To evaluate hepatic cytochrome P450 (CYP) 3A4 activity in patients infected with the human immunodeficiency virus (HIV) using the erythromycin breath test (ERMBT), and to examine the relationship of the ERMBT to plasma concentrations of indinavir and nelfinavir.

Design: Prospective observational study.

Setting: University infectious diseases clinic.

Subjects: Thirty-nine HIV-positive patients and 47 healthy controls.

Intervention: After the ERMBT in patients and controls, 25 patients received indinavir or nelfinavir.

Measurements and main results: Compared with controls, ERMBT variability was significantly greater in HIV-positive patients, including a subset of 19 patients receiving no concurrent drugs reported to alter CYP3A4 activity. Correlation between the ERMBT and first-dose plasma indinavir concentrations nearly reached statistical significance (p=0.07).

Conclusion: Variability in hepatic activity of CYP3A4 in HIV-positive patients may be greater than in controls and may explain some between-subject variability in plasma concentrations of indinavir. However, clearance mechanisms for protease inhibitors are complex, and if it is important to assess systemic exposure, the ERMBT is not a substitute for direct measurement of plasma concentrations.