The cumulative occurrence of resistance mutations in the HIV-1 protease gene is associated with failure of salvage therapy with ritonavir and saquinavir in protease inhibitor-experienced patients

Salvage therapy with ritonavir (RTV) and saquinavir (SQV) failed to achieve virological and immunological improvement in 24 HIV-infected patients who discontinued triple therapy with RTV or indinavir (IDV) because of failure or intolerance to treatment. Changes in the HIV-1 protease gene sequence we re analyzed prospectively in 14 patients. No primary protease mutation was found prior to the use of protease inhibitors. After 7 months of treatment with IDV or RTV, primary resistance mutations at codons pol 46 and/or pol 8 2 were observed in 11 of 13 patients. After 16 weeks on RTV-SQV, novel prim ary mutations related to SQV emerged in 7 of 13 patients, together with an increase in the number of secondary resistance mutations. Our observations indicate that the cumulative occurrence of resistance mutations in the prot ease gene was associated with failure of antiretroviral therapy. The presen ce of mutations to a first protease inhibitor may represent a risk factor f or the failure of a subsequent treatment with a second line protease inhibi tor. (C) 2000 Elsevier Science B.V. All rights reserved.