ACTIVITY OF A RITONAVIR PLUS SAQUINAVIR-CONTAINING REGIMEN IN PATIENTS WITH VIROLOGICAL EVIDENCE OF INDINAVIR OR RITONAVIR FAILURE

Objective: To evaluate the virologic activity of a ritonavir plus saqu inavir-containing regimen in patients who have failed an indinavir or ritonavir-containing regimen. Design: Patients were identified through a retrospective study evaluating the incidence of indinavir or ritona vir failure in our clinic. Patients: Eighteen patients failing indinav ir or ritonavir therapy and who switched to a ritonavir-saquinavir-con taining regimen were evaluated. Indinavir or ritonavir failure was def ined as a plasma viral load >1500 copies/ml (branched DNA) after 16 we eks of continuous therapy. Interventions: All patients switched to rit onavir (400 mg twice daily) plus saquinavir (400 mg twice daily) and r eceived concurrent therapy with two nucleoside reverse transcriptase i nhibitors (NRTI). Twelve of the 18 patients modified their NRTI regime n at the time ritonavir-saquinavir was initiated. Outcome measures: Pl asma viral load was monitored using a branched DNA assay. Genotypic an alysis was performed using a point mutation differential hybridization technique, and was confirmed with direct sequencing. Results: Fourtee n out of 18 patients completed at least 24 weeks of therapy; the remai ning four patients discontinued therapy after week 12 due to a lack of virologic response or intolerance. Plasma viral load decreased a medi an 1.4 log(10) after 4 weeks of treatment with ritonavir-saquinavir. O nly four patients had a greater than 0.5 log(10) decrease in viral loa d after 24 weeks of therapy. In eight out of 10 patients evaluated, th e V82A mutation was present at the time of the switch to ritonavir-saq uinavir. Viral rebound on ritonavir-saquinavir was associated with the emergence of mutations at amino acids 46, 48, 54 and 90. Conclusion: The combination of ritonavir, saquinavir and two NRTI resulted in a mo derate but transient suppression of viral replication in patients who have failed indinavir or ritonavir therapy. Failure of ritonavir-saqui navir may be associated with the emergence of mutations associated wit h resistance to ritonavir/saquinavir monotherapy, particularly the L90 M mutation. (C) 1998 Lippincott-Raven Publishers.