12th Conference on Retroviruses and Opportunistic Infections Boston, Massachusetts - February 22-25, 2005

Conf Retrovir Opportunistic Infect 2005 Feb 22-25;12:abstract no. 104

J Schapiro¹, P Cahn², B Trottier³, F Antunes⁴, D Jayaweera⁵, J Gerstoft⁶, D Norris⁷, D Cooper⁸, C Hicks⁹, S McCallister¹⁰, D Hall¹⁰, H Valdez¹⁰, D Neubacher¹⁰, V Kohlbrenner¹⁰, and D Mayers^10
1Ctr for AIDS Res, Stanford Univ Med Sch, CA, USA; ²Fndn Huésped, Buenos Aires, Argentina; ³Clin Med l' Actuel, Montreal, Canada; ⁴Hosp Santa Maria, Lisbon, Portugal; ⁵Jackson Med Ctr, Miami, FL, USA; ⁶Natl Univ Hosp, Rigshospitalet, Copenhagen, Denmark; ⁷Ctr for Quality Care, Tampa, FL, USA; ⁸St Vincent's Hosp, Univ of New South Wales, Sydney, Australia; ⁹Duke Univ Med Ctr, Durham, NC, USA; and ¹⁰Boehringer Ingelheim Pharma Inc, Ridgefield, CT, USA

BACKGROUND: Tipranavir (TPV) is a non-peptidic protease inhibitor (PI) that has demonstrated potent activity in treatment-experienced patients with resistance to available PI. The phase 3, multi-center, randomized, open-label RESIST-1 and -2 trials demonstrated superiority of TPV/ritonavir (r) over comparator/r (CPI/r). The objective of this analysis was to further evaluate the genotypic resistance profile of TPV/r relative to CPI/r.

METHODS: Patients with ≥ 3-class antiretroviral (ARV) experience including ≥ 2 PI-based ARV regimens, ≥ 1 primary PI mutation (30N, 46I/L, 48V, 50V, 82A/F/L/T, 84V, or 90M) and as many as 2 key mutations at amino acids 33, 82, 84, 90, and viral load ≥ 1000 copies/mL were eligible. 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. Protease mutations were defined as deviations from the N American Consensus Sequence B. 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.

RESULTS: We randomized and treated 1483 patients in the 2 trials, of which 1159 were available for analysis at 24 weeks. Patients had previously received a median 6 nucleoside reverse transcriptase inhibitors (NRTI), 1 non-NRTI (NNRTI), and 4 PI; 11.8% had previously taken enfuvirtide. At 24 weeks, TPV/r had a superior treatment response to CPI/r in all genotype strata (ITT-NCF); 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. 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.

CONCLUSIONS: These results indicate that the efficacy of TPV/r-based therapy was consistently superior to CPI/r in this cohort of treatment-experienced HIV+ patients regardless of the number of total baseline protease mutations, primary PI mutations, or key mutations.

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Copyright © 2005 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.