Atazanavir (Reyataz)

Published June 23, 2003; Updated October 19, 2011
Susa Coffey, MD
http://hivinsite.ucsf.edu/InSite?page=ar-03-07
Selected References
15. Colonno R, Rose R, Cianci C, Aldrovandi G, Parkin N, Friborg J. Emergence of Atazanavir Resistance and Maintenance of Susceptibility to Other PIs is Associated with an I50L Substitution in HIV Protease. 10th Conference on Retroviruses and Opportunistic Infections, Boston, February 9-14, 2003. Abstract 597.
16. Colonno  RJ, Thiry  A, Limoli  K, Parkin  N.
Activities of atazanavir (BMS-232632) against a large panel of human immunodeficiency virus type 1 clinical isolates resistant to one or more approved protease inhibitors. Antimicrob Agents Chemother. 2003 Apr;47(4):1324-33
[PubMed ID: 12654666]
Abstract:
To evaluate the cross-resistance profile of the human immunodeficiency virus type 1 protease inhibitor (PI) atazanavir (BMS-232632), a panel of 551 clinical isolates exhibiting a wide array of PI resistance profiles and a variety of genotypic patterns were assayed for susceptibility to atazanavir and six other PIs: amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir. In general, reductions in atazanavir susceptibility in vitro required several amino acid changes and were relatively modest in degree, and susceptibility was retained among isolates resistant to one or two of the currently approved PIs. There was a clear trend toward loss of susceptibility to atazanavir, as isolates exhibited increasing levels of cross-resistance to multiple PIs. Atazanavir appeared to have a distinct resistance profile relative to each of the other six PIs tested based on susceptibility comparisons against this panel of resistant isolates. Analysis of the genotypic profiles of 943 PI-susceptible and -resistant clinical isolates identified a strong correlation between the presence of amino acid changes at specific residues (10I/V/F, 20R/M/I, 24I, 33I/F/V, 36I/L/V, 46I/L, 48V, 54V/L, 63P, 71V/T/I, 73C/S/T/A, 82A/F/S/T, 84V, and 90M) and decreased susceptibility to atazanavir. While no single substitution or combination of substitutions was predictive of atazanavir resistance (change, >3.0-fold), the presence of at least five of these substitutions correlated strongly with loss of atazanavir susceptibility. Mutations associated with reduced susceptibility to each of the other six PIs were also determined.
17. Colonno R , Parkin N , McLaren C, Seekins D, Hodder S, Schnittman S, and Kelleher T. Pathways to Atazanavir Resistance in Treatment-experienced Patients and Impact of Residue 50 Substitutions. 11th Conference on Retrovirus and Opportunistic Infections, San Francisco, February 8-11,2004. Abstract 656.