Effect of widely used combinations of antiretroviral therapy on liver CYP3A4 activity in HIV-infected patients.

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Mouly S, Rizzo-Padoin N, Simoneau G, Verstuyft C, Aymard G, Salvat C, Mahe I, Bergmann JF

Effect of widely used combinations of antiretroviral therapy on liver CYP3A4 activity in HIV-infected patients.

Br J Clin Pharmacol. 2006 Aug;62(2):200-9. doi: 10.1111/j.1365-2125.2006.02637.x.

PubMed ID

16842395 [ View in PubMed

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Abstract

AIMS: To evaluate the effects of combined antiretroviral drugs (HAART) on liver CYP3A4 activity using the [(14)C-N-methyl]-erythromycin breath test (ERMBT). METHODS: HIV-infected patients (31 women, 30 men) with mean (+/- SD) age of 38 +/- 9 years were enrolled and underwent complete clinical and laboratory evaluation. Patients were divided into five groups and were treated with two nucleoside analogues (NAs) and one of the following: nelfinavir alone (n = 13), any ritonavir-boosted protease inhibitor with (n = 8) or without (n = 13) nevirapine, nevirapine alone (n = 15), or a third NA (n = 12). Three or four ERMBTs were performed 7 days prior to (D-7) and at the beginning of treatment (D0), D14 (only for patients taking nevirapine) and on D28. RESULTS: Mean baseline liver CYP3A4 activity displayed high interindividual variability (47%) but low intraindividual variability (15%). Women had 30% higher ERMBT values than men [2.7 +/- 1.3 vs. 1.9 +/- 0.7; 95% confidence interval (CI) 20.5, 49.5; P = 0.003]. The ERMBT data correlated with body weight, alpha- and beta-globulins and alanin aminotransferases (0.10 < r(s) < 0.20; P < 0.01). Whereas nevirapine had no effect on liver CYP3A4 activity, nelfinavir-based and ritonavir-boosted drug regimens inhibited it by 69% (95% CI 64.7, 72.9; P = 0.005) and by 95% (95% CI 93.3, 96.7; P = 0.001), respectively. CONCLUSION: Evaluation of the effect of HAART on liver CYP3A4 activity may aid in preventing inappropriate treatment regimens in HIV-infected patients.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Indinavir	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inhibitor	Details
Nevirapine	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate Inducer	Details