Influence of tenofovir, nevirapine and efavirenz on ritonavir-boosted atazanavir pharmacokinetics in HIV-infected patients

Objective: The influence of nevirapine, efavirenz and tenofovir co-administration on ritonavir-boosted atazanavir pharmacokinetics was investigated in HIV (human immunodeficiency virus)-infected patients. Methods: A population pharmacokinetic analysis was performed in the context of therapeutic drug monitoring (87 patients, 121 samples). Results: A significant increase of atazanavir clearance (Cl/F) was found when either tenofovir (group B), efavirenz (group C), or nevirapine (group D) were co administered with atazanavir/ritonavir in comparison with patients treated with atazanavir/ritonavir and nucleoside reverse transcriptase inhibitors (group A): 6.24 +/- 0.36 l h(-1) (group A) versus 7.42 +/- 0.25 l h(-1) (group B) versus 9.60 +/- 0.27 l h(-1) (group C) versus 17.53 +/- 0.57 l h(-1) (group D) (P < 0.001). However, the decrease of the mean trough plasma concentration of atazanavir was significant only in group D: 1.02 +/- 0.86 mg/l (group A) versus 0.21 +/- 013 mg/l (group D) (P < 0.001). Conclusion: The increase in atazanavir clearance when it is used in combination with nevirapine, efavirenz and/or tenofovir suggests that therapeutic drug monitoring of atazanavir should be performed in such circumstances.