The efficacy of
HIV-1 protease inhibitors (PIs) as part of
highly active antiretroviral therapy is now well established and has provided benefits to many patients with
HIV infection.
Atazanavir is a new azapeptide PI compound that was recently approved in the US and Europe.
Atazanavir is recommended in combination with other
antiretroviral agents for the treatment of HIV-1
infection.
Atazanavir is rapidly absorbed and administration of a single dose of
atazanavir with a light meal resulted in a 70% increase in area under the plasma concentration-time curve (AUC); therefore
atazanavir should be taken with food.
Atazanavir is 86% bound to human
serum protein independently of concentration. Concentration in body fluids appeared to be lower than plasma concentration. Like other PIs,
atazanavir is extensively metabolised by hepatic
cytochrome P450 (CYP) 3A
isoenzymes. The mean terminal elimination half-life in healthy volunteers was approximately 7 hours at steady state following administration of
atazanavir 400 mg daily with a light meal. When
atazanavir 300 mg was coadministered with
ritonavir 100 mg on a once-daily dosage regimen,
atazanavir AUC from 0 to 24 hours and minimum plasma concentration were increased by 3- to 4-fold and approximately 10-fold, respectively, compared with
atazanavir 300 mg alone. Therefore,
ritonavir boosted
atazanavir regimen (
ritonavir 100 mg and
atazanavir 300 mg once daily) is increasingly favoured in some patients.
Efavirenz, a potent
CYP3A inducer, decreased
atazanavir concentrations by 75% and, unexpectedly,
tenofovir, a
nucleotide reverse transcriptase inhibitor, decreased
atazanavir concentrations by 25%. Average predose concentrations in HIV-infected patients who received
atazanavir 400mg once daily were 273 ng/mL, which was believed to be several-fold higher than protein-binding corrected 50% inhibitory concentration of wild-type viruses. In HIV-infected patients who received once-daily
ritonavir (100mg) boosted
atazanavir (300 mg), mean (+/-SD) trough concentration was 862 (+/-838) ng/mL. Several clinical trials showed the efficacy of
atazanavir 400 mg once daily with a
nucleoside analogue backbone in antiretroviral-naive patients. The
atazanavir 300/
ritonavir 100 mg once-daily combination coadministered with other antiretrovirals showed the efficacy of this strategy in patients receiving
efavirenz or in moderately antiretroviral-experienced HIV-infected patients. Recommended once-daily doses of
atazanavir taken with food are either 400 mg or 300 mg in combination with low dose
ritonavir (100 mg) in moderately antiretroviral-experienced patients. Major advantages of
atazanavir to date are its simplicity of administration (once-daily administration) and its less undesirable effect on the
lipid profiles in patients.