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Choosing When to Use Tipranavir
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12th CROI Feb 2005
Reported for NATAP by David Margolis, MD
Univ of Texas, Southwestern Medical Center Dallas; VA Dallas; ACTG
Jonathan Schapiro (abstr. 104) presented resistance data from the pivotal tipranavir RESIST trials for Boehringer Ingelheim. More than 100 patients were studied in these phase 3, multi-center, randomized, open-label trials which demonstrated superiority of TPV/ritonavir over an investigator-selected comparator boosted PI.
Patients enrolled has ≥ 3-class antiretroviral experience including ≥ 2 PI-based ARV regimens, ≥ 1 primary PI mutation (30N, 46I/L, 48V, 50V, 82A/F/L/T, 84V, or 90M), no more than 2 key mutations at amino acids 33, 82, 84, 90, and viral load ≥ 1000 copies/mL. Before randomization, an optimized CPI/r regimen was selected from among LPV, IDV, SQV, or APV. Patients were then randomized to TPV/r (500 mg/200 mg twice daily) or CPI/r. Resistance was determined from genotypic interpretation of TruGene or VirtualPhenotype assays. This planned interim analysis compared the effect of baseline genotype on the efficacy of TPV/r and CPI/r. The primary endpoint (treatment response) was defined as a confirmed ≥ 1 log decrease in viral load from baseline without prior treatment changes.
1483 patients were treated in RESIST 1 and 2, of which 1159 were available for analysis at 24 weeks. Patients had previously received a median of 12 ARV's. At 24 weeks, TPV/r had a superior treatment response to CPI/r in all genotype strata (ITT-NCF); 41.2% vs. 18.9% responding. When analyzed by number of mutations, 50.4% vs 29.8% with ≤ 12 protease gene mutations, 39.4% vs 26.3% with 13 to 15, 43.6% vs 13.0% with 16 to 18, and 31.7% vs 7.7% with ≥ 19 mutations responded. Similarly, treatment response to TPV/r was not affected by the number of primary PI mutations, with > 40% of patients whose virus had up to 6 primary PI mutations achieving treatment response. This compared with 28% of CPI/r patients with 1 to 2 of these mutations, 13.6% with 3 to 4, and 16.7% with 5 to 6. There was no difference in treatment response in the presence of 0 key mutations. However, with 1 to 2 key mutations, 44.2% vs 25% and 40.9% vs 15.3% had treatment response in the TPV/r and CPI/r groups respectively.
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