TITAN Trial Darunavir/r versus Lopinavir/r in Treatment-Experienced - PowerPoint PPT Presentation

Darunavir + RTV versus Lopinavir-RTV in Treatment Experienced TITAN Trial

Darunavir/r versus Lopinavir/r in Treatment-Experienced TITAN: Study Design Study Design: TITAN • Background : Randomized, controlled, open-label, Darunavir 600 mg BID phase 3 trial to compare the efficacy and safety of + Ritonavir 100 mg BID ritonavir-boosted darunavir versus lopinavir- + OBR ritonavir, both with OBR*, in treatment-experienced, (n = 298) lopinavir-naïve patients with HIV infection • Inclusion Criteria (n=595) - Adults ≥18 years - HIV RNA ≥500 copies/mL Lopinavir/ritonavir 400/100 mg BID - Treatment-experienced, lopinavir naïve + OBR (n = 297) • Treatment Arms - Darunavir 600 mg BID + RTV 100 mg BID + OBR* - Lopinavir/ritonavir (400/100 mg) BID + OBR* TITAN = T MC114/r I n T reatment-experienced p A tients N aïve to lopinavir *OBR = Optimized background regimen: ≥ 2 active antiretroviral agents Source: Madruga JV, et al. Lancet. 2007;370:49-58.

Darunavir/r versus Lopinavir/r in Treatment-Experienced TITAN: Study Participant ARV Treatment History Prior Number of Protease Inhibitors Most Frequently Used Prior PIs 60 0 1 Prior Protease Inhibitor (%) 50 ≥2 40 38% 35 31% 28 30 24 20 31% 10 0 Indinavir Nelfinavir Saquinavir Protease Inhibitor Source: Madruga JV, et al. Lancet. 2007;370:49-58.

Darunavir/r versus Lopinavir/r in Treatment-Experienced TITAN: Result Week 48: Virologic Response ( ITT-TLOVR) Darunavir + Ritonavir + OBR Lopinavir-Ritonavir + OBR 100 HIV RNA <50 copies/mL (%) 80 74 71 63 60 55 60 48 40 20 P = 0.005 0 ≥ 100,000 copies/mL All < 100,000 copies/mL Baseline HIV RNA Source: Madruga JV, et al. Lancet. 2007;370:49-58.

Darunavir/r versus Lopinavir/r in Treatment-Experienced TITAN: Result Week 48: Virologic Response, by Baseline PI Resistance ( ITT-TLOVR) Darunavir + Ritonavir + OBR Lopinavir-Ritonavir + OBR 100 HIV RNA < 50 copies/mL (%) 80 72 70 70 63 60 59 60 50 40 28 20 0 Lopinavir FC ≤10 Darunavir FC ≤10 Lopinavir FC >10 Darunavir FC >10 Baseline Resistance Source: Madruga JV, et al. Lancet. 2007;370:49-58.

Darunavir/r versus Lopinavir/r in Treatment-Experienced TITAN: Conclusions Interpretation : “In lopinavir-naïve, treatment-experienced patients, darunavir-ritonavir was non-inferior to lopinavir-ritonavir treatment in terms of our virological endpoint, and should therefore be considered as a treatment option for this population.” Source: Madruga JV, et al. Lancet. 2007;370:49-58.

Darunavir/r versus Lopinavir/r in Treatment-Experienced TITAN (Characterization of Virologic Failure): Result Week 48: Virologic Response, by Baseline Darunavir-Associated RAMs Darunavir + Ritonavir +OBR Lopinavir-Ritonavir + OBR 100 97 HIV RNA <400 copies/mL 91 90 89 80 83 79 74 60 60 46 40 36 20 0 ≥3 All Patients None 1 2 Number of Baseline Darunavir-Associated Mutations Source: De Meyer S, et al. AIDS. 2009;23:1829-40.

Darunavir/r versus Lopinavir/r in Treatment-Experienced TITAN (Characterization of Virologic Failure): Conclusions Conclusion : “In treatment -experienced, LPV-naive patients, the overall virologic failure rate in the DRV/r arm was low and was associated with limited resistance development. These findings showed that the use of DRV/r in earlier lines of treatment was less likely to lead to cross- resistance to other protease inhibitors compared with LPV/r.” Source: De Meyer S, et al. AIDS. 2009;23:1829-40.

Acknowledgment The National HIV Curriculum is an AIDS Education and Training Center (AETC) Program resource funded by the United States Health Resources and Services Administration. The project is led by the University of Washington and the AETC National Coordinating Resource Center. The content in this slide set does not represent the official views of the U.S. Department of Health and Human Services, Health Resources & Services Administration.