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Effect of widely used combinations of antiretroviral therapy on liver CYP3A4 activity in HIV‐infected patients
Author(s) -
Mouly Stéphane,
RizzoPadoin Nathalie,
Simoneau Guy,
Verstuyft Céline,
Aymard Guy,
Salvat Cécile,
Mahé Isabelle,
Bergmann JeanFrançois
Publication year - 2006
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2006.02637.x
Subject(s) - nevirapine , ritonavir , nelfinavir , gastroenterology , medicine , cyp3a4 , confidence interval , protease inhibitor (pharmacology) , pharmacology , human immunodeficiency virus (hiv) , viral load , immunology , antiretroviral therapy , cytochrome p450 , metabolism
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, α‐ and β‐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.