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

Conf Retrovir Opportunistic Infect 2005 Feb 22-25;12:abstract no. 560

D Cooper¹, 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 McCallister^12
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.

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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.