560 24-Week RESIST Study Analyses: the Efficacy of Tipranavir/Ritonavir Is Superior to Lopinavir/Ritonavir, and the TPV/r Treatment Response is Enhanced by Inclusion of Genotypically Active Antiretrovirals in the Optimized Background Regimen D Cooper*1, C Hicks2, P Cahn3, A Lazzarin4, S Walmsley5, K Arasteh6, C Katlama7, B Grinsztejn8, S Moreno9, N Clumeck10, P Lopez11, G Mukwaya12, J Villacian12, V Kohlbrenner12, and S McCallister12 1St Vincent's Hosp, Univ of New South Wales, Sydney, Australia; 2Duke Univ Med Ctr, Durham, NC, USA; 3Fndn Huésped, Buenos Aires, Argentina; 4Fndn Centro San Raffaele del Monte Tabor, Milan, Italy; 5Toronto Gen Hosp, Canada; 6Epimed GmbH, c/o Vivantes Auguste-Viktoria Hosp, Berlin, Germany; 7Hosp Pitie-Salpetriere, Paris, France; 8Oswaldo Cruz Inst, Fiocruz, Rio de Janeiro, Brazil; 9Hosp Ramon y Cajal, Madrid, Spain; 10Ctr Hosp Univ, Univ Med Ctr, Brussels, Belgium; 11Ctr Guadalajara, Mexico City, Mexico; and 12Boehringer Ingelheim Pharma Inc, Ridgefield, CT, USA

Background:  RESIST-1 and -2 are ongoing phase 3, multicenter, open-label trials in treatment-experienced patients randomized to a standard-of-care regimen containing either a boosted comparator protease inhibitor (PI) (CPI/r) or tipranavir/ritonavir (TPV/r). The objective of this analysis was to compare the efficacy of TPV/r and lopinavir/ritonavir(LPV/r), and to assess the role of additional active drugs in the optimized background regimen (OBR).

Methods:  Patients with ≥ 3-class antiretroviral therapy (ART) experience, including ≥ 2 PI-based ART regimens, and ≥ 1 primary PI mutation but ≤ 2 at amino acids 33, 82, 84, 90, and viral load ³ 1000 copies/mL were eligible. Before randomization, an optimized CPI/r regimen (that could include enfuvirtide [T20] in the OBR) was selected. Patients then received either TPV/r (500 mg/200 mg bid) or the preselected CPI/r plus the OBR. The TPV/r and LPV/r treatment response was compared and the effect of active ART in the OBR was evaluated. Active drugs were defined as those with predicted ART sensitivity based on interpretation of TruGene^® or VirtualPhenotype™ assays. Treatment response was defined as a confirmed ≥ 1 log₁₀ decrease in viral load from baseline.

Results:  We randomized and treated 1483 patients in the 2 trials, of which 1159 were available for analysis at 24 weeks. Median baseline values were:  viral load, 4.8 log₁₀ copies/mL; CD4⁺ cell count, 162 cells/mm³; number of protease gene mutations, 16. Patients had previously received a median 12 prior ART; 11.9% of all patients had taken T20; 50% of investigators preselected LPV/r as optimized CPI/r and LPV was a new PI in 42% in this stratum. At 24 weeks, treatment response (ITT-NCF) was seen in 39.6% (116 of 293) and 21.4% (62 of 290) in the TPV/r and LPV/r groups, respectively (p < 0.05); 34% and 18%, respectively, had viral loads < 400 copies/mL, and CD4⁺ increase was 31 cells/mm³ and 6 cells/mm³, respectively. The 24-week treatment response increased in both the TPV/r and CPI/r groups with the use of more active background ART:  0 active background ART used (13.1% vs 9.1%, respectively), 1 (37.4% vs 12.9%), 2 (46.2% vs 19.9%), or ≥ 3 (54.7% vs 34.3%); 24.7% of patients used T20. At week 24, the treatment response in patients using T20 was:  TPV/r arm, 58.2%; CPI/r arm, 25.8%. The treatment response in patients not using T20 was:  TPV/r arm, 34.9%; CPI/r arm, 16.9%. 

Conclusions:  The 24-week RESIST study results indicate that TPV/r was superior to LPV/r across multiple efficacy variables in these PI-experienced HIV⁺ patients. The TPV/r treatment response is enhanced when combined with additional active ART.

Keywords: Tipranavir; Enfuvirtide; Protease Inhibitor