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Role of atazanavir in the treatment of HIV infection

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Author(s): Pablo Rivas | Judit Morello | Carolina Garrido | Sonia Rodríguez-Nóvoa | Vincent Soriano

Journal: Therapeutics and Clinical Risk Management
ISSN 1176-6336

Volume: 2009;
Issue: default;
Start page: 99;
Date: 2008;
Original page

ABSTRACT
Pablo Rivas1, Judit Morello2, Carolina Garrido1, Sonia Rodríguez-Nóvoa2, Vincent Soriano11Department of Infectious Diseases; 2Pharmacology Unit, Hospital Carlos III, Madrid, SpainAbstract: 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).Keywords: atazanavir, HIV, protease inhibitors, drug resistance

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