Atazanavir: simplicity and convenience in different scenarios

Abstract

HIV protease inhibitors (PI) have undergone the most significant evolution when considering the different families of antiretrovirals. Marketed in 2003, atazanavir (ATV) is the first azapeptide PI, and is considered a member of the second generation of PIs. Important characteristics make ATV different from other drugs in the same family of antiretrovirals. It is administered once daily, either as two capsules (200 mg) or boosted with ritonavir (100 mg) two capsules (150 mg) or one capsule (300 mg). No elevations in serum levels of total cholesterol, low-density lipoprotein cholesterol or triglycerides have been observed with unboosted ATV. Although some increases in these levels are found with boosted ATV, these were lower when compared with other PIs. Elevation in unconjugated bilirubin levels, which is usually not dose limiting, is the most frequent adverse event. Naive patients receiving ATV boosted with ritonavir do not develop PI mutations at failure, whereas unboosted ATV in the same scenario induces the I50L mutation, which does not confer cross-resistance to other PIs. The best scenario for unboosted ATV is simplification. In PI treatment-experienced patients with PI mutations, susceptibility to ATV is usually reduced, so it should be administered with ritonavir. As with other PIs, careful attention must be given to pharmacokinetic drug interactions; the coadministration of certain commonly used drugs among HIV-infected patients, tenofovir and members of the proton pump inhibitor family, leads to significantly lower plasma levels of ATV.