Although recent discussion of atazanavir use has tended to predict that the new protease inhibitor will find its niche as a first line protease inhibitor, a study published last week in the April issue of Antimicrobial Agents and Chemotherapy suggests that a substantial proportion of individuals who have experienced failure of nelfinavir, and to a lesser extent, of one other PI, are still likely to be susceptible to atazanavir.
A team from ViroLogic and Bristol Myers Squibb (the manufacturer of atazanavir) analysed protease inhibitor susceptibility in a panel of 551 clinical isolates derived from protease inhibitor-experienced patients screened to join studies of atazanavir in combination with ritonavir or saquinavir.
Loss of atazanavir susceptibility was correlated with mutations at the following protease codons: 10I/V/F, 20R/M/I, 24I, 33I/F/V, 46I/L, 48V, 54V/L, 63P, 71V/T/I, 73C/S/T/A, 82A/F/S/T, 84V, and 90M. The presence of substitutions at more than five of these positions was associated with greater than threefold loss of susceptibility to atazanavir in the vast majority of isolates (81.3%).
86% of 214 isolates resistant to one or two protease inhibitors were still susceptible to atazanavir (
25% of 195 isolates resistant to three or four protease inhibitors were still susceptible to atazanavir. In comparison, 61% of these isolates were still susceptible to amprenavir, 11% to indinavir, 42% to lopinavir, 8% to nelfinavir, 1% to ritonavir and 49% to saquinavir.
Further discussion of the use of atazanavir
ClinicalCare Options for HIV website – panel discussion of resistance and salvage therapy data from the Tenth Conference on Retroviruses and Opportunistic Infections
Colonno R et al. 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. Antimicrobial Agents and Chemotherapy 47 (4): 1324-33, 2003.