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

Source: Madruga JV, et al. Lancet. 2007;370:49-58.

Darunavir 600 mg BID + Ritonavir 100 mg BID + OBR

(n = 298)

Lopinavir/ritonavir 400/100 mg BID + OBR

(n = 297)

Study Design: TITAN

• Background: Randomized, controlled, open-label,

phase 3 trial to compare the efficacy and safety of ritonavir-boosted darunavir versus lopinavir- ritonavir, both with OBR*, in treatment-experienced, lopinavir-naïve patients with HIV infection

• Inclusion Criteria (n=595)
• Adults ≥18 years
• HIV RNA ≥500 copies/mL
• Treatment-experienced, lopinavir naïve
• Treatment Arms
• Darunavir 600 mg BID + RTV 100 mg BID + OBR*
• Lopinavir/ritonavir (400/100 mg) BID + OBR*

TITAN = TMC114/r In Treatment-experienced pAtients Naïve to lopinavir *OBR = Optimized background regimen: ≥2 active antiretroviral agents

Darunavir/r versus Lopinavir/r in Treatment-Experienced

TITAN: Study Participant ARV Treatment History

Source: Madruga JV, et al. Lancet. 2007;370:49-58.

35 28 24

10 20 30 40 50 60 Indinavir Nelfinavir Saquinavir Prior Protease Inhibitor (%) Protease Inhibitor

31% 38% 31%

1 ≥2

Prior Number of Protease Inhibitors Most Frequently Used Prior PIs

Darunavir/r versus Lopinavir/r in Treatment-Experienced

TITAN: Result

Week 48: Virologic Response ( ITT-TLOVR)

Source: Madruga JV, et al. Lancet. 2007;370:49-58.

71 74 55 60 63 48

20 40 60 80 100 All < 100,000 copies/mL ≥ 100,000 copies/mL HIV RNA <50 copies/mL (%) Darunavir + Ritonavir + OBR Lopinavir-Ritonavir + OBR Baseline HIV RNA

P = 0.005

Darunavir/r versus Lopinavir/r in Treatment-Experienced

TITAN: Result

Week 48: Virologic Response, by Baseline PI Resistance ( ITT-TLOVR)

Source: Madruga JV, et al. Lancet. 2007;370:49-58.

70 72 70 60 63 28 59 50 20 40 60 80 100

Lopinavir FC ≤10 Lopinavir FC >10 Darunavir FC ≤10 Darunavir FC >10

HIV RNA < 50 copies/mL (%) Baseline Resistance Darunavir + Ritonavir + OBR Lopinavir-Ritonavir + OBR

Darunavir/r versus Lopinavir/r in Treatment-Experienced

TITAN: Conclusions

Source: Madruga JV, et al. Lancet. 2007;370:49-58.

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.”

Darunavir/r versus Lopinavir/r in Treatment-Experienced

TITAN (Characterization of Virologic Failure): Result

Week 48: Virologic Response, by Baseline Darunavir-Associated RAMs

Source: De Meyer S, et al. AIDS. 2009;23:1829-40.

90 91 97 89 60 79 83 74 36 46 20 40 60 80 100

All Patients None 1 2 ≥3

HIV RNA <400 copies/mL Number of Baseline Darunavir-Associated Mutations Darunavir + Ritonavir +OBR Lopinavir-Ritonavir + OBR

Darunavir/r versus Lopinavir/r in Treatment-Experienced TITAN (Characterization of Virologic Failure): Conclusions

Source: De Meyer S, et al. AIDS. 2009;23:1829-40.

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.”

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.