Atazanavir (ATV) is one of the latest
protease inhibitors (PI) approved for the treatment of
HIV infection. The
drug has a relatively long-life (~7 h) and large inhibitory quotient which allows once daily administration. It is generally well tolerated and the main side effect is
hyperbilirubinemia, since ATV inhibits the hepatic uridin-glucoronyl-
transferase. A signature mutation at the
protease gene, I50L, may confer loss of susceptibility to the
drug. Interestingly, it produces hypersusceptibility to all other PIs. When ATV is pharmacokinetically boosted with
ritonavir (r) 100 mg/day, a greater genetic barrier for resistance is achieved, and generally more than 3 major PI resistance associated mutations are needed to result in ATV resistance. In
drug-naïve subjects, regimens based on ATV/r have shown non-inferiority compared to
lopinavir (LPV)/r (CASTLE study) or
fosamprenavir/r (ALERT trial), generally with improved tolerance (less
diarrhea and
dyslipidemia). Given its good tolerance and convenience, ATV has been proven to be successful as a simplification strategy in switch studies (ie, SWAN and SLOAT) conducted in patients with complete virological suppression under other PI-based regimens. Finally, ATV/r-based combinations have shown to be equivalent in terms of viral response to other PI/r-containing regimens, including LPV/r, in rescue interventions in patients failing other PI regimens (ie, studies AI424-045 and NADIS).