Atazanavir: improving the HIV protease inhibitor class

Abstract

Protease inhibitors are potent agents against HIV but their use is constrained by poor pharmacokinetics, cross-resistance and metabolic toxicities. Atazanavir [Reyataz™] is a new protease inhibitors with once-daily dosing and minimal lipid and glycemic effects. Resistance studies of clinical isolates reveal a mutational pattern distinctive from that of other protease inhibitors. Atazanavir selects for the I50L mutation in HIV protease that confers increased susceptibility to other protease inhibitors in vitro. Clinical trials have shown comparable efficacy to nelfinavir (Viracept®) and efavirenz (Sustiva®) in treatment-naive patients, and in preliminary studies, ritonavir-boosted atazanavir is effective in patients failing previous protease inhibitor-containing regimens. Reversible elevations in bilirubin occur in some patients but are not associated with hepatic injury. Atazanavir improves upon aspects of currently-available protease inhibitors and appears useful for initial and possibly subsequent HIV therapy.