Abstract and Introduction
Atazanavir is the first once-daily protease inhibitor for the treatment of human immunodeficiency virus type 1 infection and should be used only in combination therapy, as part of a highly active antiretroviral therapy (HAART) regimen. In addition to being the most potent protease inhibitor in vitro, atazanavir has a distinct cross-resistance profile that does not confer resistance to other protease inhibitors. However, resistance to other protease inhibitors often confers clinically relevant resistance to atazanavir. Currently, atazanavir is not a preferred protease inhibitor for initial HAART regimens. In treatment-naïve patients, atazanavir can be given as 400 mg/day. However, atazanavir should be pharmacologically boosted with ritonavir in treatment-experienced patients or when coadministered with either tenofovir or efavirenz. Patients who receive atazanavir experience similar rates of adverse events compared with patients receiving comparator regimens. An exception is an increased risk of asymptomatic hyperbilirubinemia, which is due to competitive inhibition of uridine diphosphate-glucuronosyltransferase 1A1. Although hyperbilirubinemia is a common adverse drug reaction of atazanavir therapy (22-47%), fewer than 2% of patients discontinue atazanavir therapy because of this adverse effect. Common adverse effects reported with atazanavir include infection, nausea, vomiting, diarrhea, abdominal pain, headache, peripheral neuropathy, and rash. Of significance, fewer abnormalities have been observed in plasma lipid profiles in patients treated with atazanavir compared with other protease inhibitor-containing regimens. As with other protease inhibitors, atazanavir is also a substrate and moderate inhibitor of the cytochrome P450 (CYP) system, in particular CYP3A4 and CYP2C9. Clinically significant drug interactions include (but are not limited to) antacids, proton pump inhibitors, histamine type 2 receptor antagonists, tenofovir, diltiazem, irinotecan, simvastatin, lovastatin, St. John's wort, and warfarin. We conclude that atazanavir is a distinctively characteristic protease inhibitor owing to its in vitro potency, once-daily dosing, distinct initial resistance pattern, and infrequent association with metabolic abnormalities.
The introduction of highly active antiretroviral therapy (HAART) has significantly reduced the morbidity and morality related to human immunodeficiency virus (HIV) infection.[1,2] Protease inhibitors, along with a backbone of two nucleoside reverse transcriptase inhibitors (NRTIs), are still considered to be a preferred regimen for the treatment of antiretroviral-naïve patients who are HIV positive.[3] Such HAART regimens can suppress plasma HIV RNA to undetectable levels (< 50 RNA copies/ml) but may be associated with long-term complications. Such complications may include metabolic abnormalities such as glucose intolerance, insulin resistance, dyslipidemia, and abnormal fat distribution. It is feared that these adverse reactions may lead to coronary artery disease and, ultimately, higher rates of cardiovascular events.[4,5,6] In addition, antiretroviral therapy is a difficult undertaking due to drug-related adverse events, nonadherence to therapy, the evolution of antiretroviral-resistant HIV, and clinically significant drug interactions.[3,7,8,9]
The recent approval of atazanavir sulfate (Reyataz; Bristol-Myers Squibb Company, Princeton, NJ), offers some distinct advantages compared with current protease inhibitors. Atazanavir is an azapeptide protease inhibitor with a pharmacokinetic profile that allows once-daily dosing, it has a distinctive resistance profile, and its use may result in fewer metabolic complications.
Pharmacotherapy. 2004;24(12) © 2004 Pharmacotherapy Publications
Copyright © 1999, Pharmacotherapy Publications, Inc., All rights reserved.
Cite this: Atazanavir for the Treatment of Human Immunodeficiency Virus Infection - Medscape - Dec 01, 2004.
