Clinical pharmacology, efficacy and safety of atazanavir: a review

Background: Atazanavir (ATV) is a potent and safe protease inhibitor (PI) initially approved in adult HIV-1 infected patients in combination with other antiretroviral drugs with once daily administration. In combination with nucleoside reverse transcriptase inhibitors (NRTIs) and boosted with ritonavir, it has been established as the preferred initial regimen in published guidelines. Objective: This article reviews relevant pharmacodynamic, pharmacokinetic, efficacy and safety data of ATV, administered boosted with ritonavir or unboosted, in comparison with other Pis and/or non-NRTIs, with special focus on recent studies. Methods: Review articles, recent primary literature and scientific meeting reports were analyzed. Results: Compared to most Pis with similar efficacy, the advantages of ATV are a once daily administration with only 100 mg ritonavir when boosted, a good gastrointestinal tolerance with limited diarrhea, a neutral effect on cholesterol and triglycerides, and a favorable resistance profile. However, highly frequent hyperbilirubinemia is observed resulting in some cases in clinical jaundice. Unboosted ATV must be cautiously used because increased resistances have been described. Conclusion: The combination of a similar efficacy, a better tolerance and a low pill burden, as compared to other Pls, makes boosted ATV one of the best options, in combination with NRTIs, in PI-naive HIV-1 infected patients.