Darunavirr versus Other PIs in Treatment Experienced POWER

Darunavir/r versus Other PIs in Treatment Experienced POWER 1 and 2

Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Study Design: POWER 1 and 2 • Background: Two randomized, phase 2 b trials to compare the efficacy and safety of ritonavir-boosted darunavir with other protease inhibitors in treatmentexperienced HIV-infected patients with PI resistance • Inclusion Criteria (n = 155) - Age ≥ 18 - HIV RNA >1000 copies/m. L - On PI-containing regimen - History of taking >1 NRTI, and ≥ 1 NNRTI as part of failing regimen - At least 1 primary PI mutation at screening • Treatment Arms - Darunavir 600 mg BID + Ritonavir 100 mg bid + OBR* - Investigator-selected control PI + OBR* *OBR = Optimized background regimen: ≥ 2 NRTIs +/- enfurvirtide Source: Clotet B, et al. Lancet. 2007; 369: 1169 -78. Darunavir BID + RTV BID + OBR (n = 131) Control PI + RTV + OBR (n =124)

Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Result Week 48: Virologic Response Darunavir + RTV + OBR Control PI + RTV + OBR Patients Success (%) 100 80 60 61 45 40 15 20 0 67/110 18/120 ≥ 1 log 10 Decrease in HIV RNA Source: Clotet B, et al. Lancet. 2007; 369: 1169 -78. 10 50/110 12/120 HIV RNA <50 copies/m. L

Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Result HIV RNA reduction ≥ 1· 0 log 10 copies per m. L from baseline (%) Week 48: Virologic Response ( ITT-TLOVR) Darunavir + RTV + OBR 100 Control PI + RTV + OBR 83 80 60 66 61 41 40 24 15 20 0 All 13 ≤ 20, 000 -100, 000 6 ≥ 100, 000 Baseline HIV RNA (copies/m. L) Source: Clotet B, et al. Lancet. 2007; 369: 1169 -78.

Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Result Week 48: Virologic Response, by Primary PI Mutations at Baseline Darunavir + RTV + OBR HIV RNA <50 copies/m. L (%) 100 80 Control PI + RTV + OBR 67 60 44 44 40 19 20 17 5 0 ≤ 1 2 Number of Primary PI Mutations Source: Clotet B, et al. Lancet. 2007; 369: 1169 -78. ≥ 3

Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Result Week 48: Virologic Response, by DRV-Associated Mutations at Baseline Darunavir + RTV + OBR HIV RNA <50 copies/m. L (%) 100 Control PI + RTV + OBR 80 60 56 46 40 26 17 20 0 7 ≤ 1 2 3 ≥ 3 Number of Darunavir-Associated Mutations Source: Clotet B, et al. Lancet. 2007; 369: 1169 -78.

Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Result ACTG Grade 3 or 4 Adverse Events (≥ 1% incidence regardless of causality) DRV + RTV + OBR Control PI + RTV + OBR (n = 131) (n = 124) Abdominal pain 3 0 Neutropenia 2 3 Diarrhea 2 2 Injection site reaction (2° enfuvirtide) 2 1 Acute renal failure 2 1 Hip arthroplasty 2 0 Peripheral neuropathy 2 0 Anemia 2 0 Weight decreased 2 0 Pneumonia 2 0 Fatigue 1 2 Hyperbilirubinemia 0 3 Herpes zoster 0 2 Data given for Number of Patients Source: Clotet B, et al. Lancet. 2007; 369: 1169 -78.

Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Conclusions Interpretation: “Efficacy responses with darunavir-ritonavir 600/100 mg twice daily plus optimised background regimen were greater than those with control PI and were sustained to at least week 48, with favourable safety and tolerability in treatment-experienced patients. This regimen could expand the treatment options available for such patients. ” Source: Clotet B, et al. Lancet. 2007; 369: 1169 -78.

Darunavir/r versus other PIs in Treatment-Experienced POWER 1 and 2: Result Week 24: Virologic Response, by Viral Susceptibility at Baseline HIV RNA <50 copies/m. L (%) 100 80 60 45 40 51 41 24 20 7 0 0 All patients Darunavir FC ≤ 10 11 -40 >40 Darunavir + RTV + OBR ≥ 1 active c. PI No active c. PIs Control PIs Source: Posniak A, et al. AIDS Res Hum Retroviruses. 2008; 24: 1275 -80.

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.