POWER 1 and 2 Darunavir/r versus other PIs in Treatment-Experienced - - PowerPoint PPT Presentation

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

Source: Clotet B, et al. Lancet. 2007;369:1169-78.

Darunavir BID + RTV BID + OBR

(n = 131)

Control PI + RTV + OBR

(n =124)

Study Design: POWER 1 and 2

• Background: Two randomized, phase 2b trials to

compare the efficacy and safety of ritonavir-boosted darunavir with other protease inhibitors in treatment- experienced HIV-infected patients with PI resistance

• Inclusion Criteria (n = 155)
• Age ≥18
• HIV RNA >1000 copies/mL
• 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

Darunavir/r versus other PIs in Treatment-Experienced

POWER 1 and 2: Result

Week 48: Virologic Response

Source: Clotet B, et al. Lancet. 2007;369:1169-78.

61 45 15 10 20 40 60 80 100 ≥1 log10 Decrease in HIV RNA HIV RNA <50 copies/mL Patients Success (%) Darunavir + RTV + OBR Control PI + RTV + OBR

50/110 12/120 67/110 18/120

Darunavir/r versus other PIs in Treatment-Experienced

POWER 1 and 2: Result

Week 48: Virologic Response ( ITT-TLOVR)

Source: Clotet B, et al. Lancet. 2007;369:1169-78.

61 83 41 66 15 24 13 6 20 40 60 80 100

All ≤20,00 20,000-100,000 ≥100,000 HIV RNA reduction ≥1·0 log10 copies per mL from baseline (%)

Darunavir + RTV + OBR Control PI + RTV + OBR

Baseline HIV RNA (copies/mL)

Darunavir/r versus other PIs in Treatment-Experienced

POWER 1 and 2: Result

Week 48: Virologic Response, by Primary PI Mutations at Baseline

Source: Clotet B, et al. Lancet. 2007;369:1169-78.

67 44 44 19 17 5 20 40 60 80 100

≤1 2 ≥ 3

HIV RNA <50 copies/mL (%)

Number of Primary PI Mutations

Darunavir + RTV + OBR Control PI + RTV + OBR

Darunavir/r versus other PIs in Treatment-Experienced

POWER 1 and 2: Result

Week 48: Virologic Response, by DRV-Associated Mutations at Baseline

Source: Clotet B, et al. Lancet. 2007;369:1169-78.

56 46 26 17 7 3 20 40 60 80 100

≤1 2 ≥ 3

HIV RNA <50 copies/mL (%)

Number of Darunavir-Associated Mutations

Darunavir + RTV + OBR Control PI + RTV + OBR

Darunavir/r versus other PIs in Treatment-Experienced

POWER 1 and 2: Result

Source: Clotet B, et al. Lancet. 2007;369:1169-78.

ACTG Grade 3 or 4 Adverse Events (≥ 1% incidence regardless of causality) Data given for Number of Patients DRV + RTV + OBR

(n = 131)

Control PI + RTV + OBR

(n = 124)

Abdominal pain 3 Neutropenia 2 3 Diarrhea 2 2 Injection site reaction (2° enfuvirtide) 2 1 Acute renal failure 2 1 Hip arthroplasty 2 Peripheral neuropathy 2 Anemia 2 Weight decreased 2 Pneumonia 2 Fatigue 1 2 Hyperbilirubinemia 3 Herpes zoster 2

Darunavir/r versus other PIs in Treatment-Experienced

POWER 1 and 2: Conclusions

Source: Clotet B, et al. Lancet. 2007;369:1169-78.

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.”

Darunavir/r versus other PIs in Treatment-Experienced

POWER 1 and 2: Result

Week 24: Virologic Response, by Viral Susceptibility at Baseline

Source: Posniak A, et al. AIDS Res Hum Retroviruses. 2008;24:1275-80.

45 51 41 24 7 20 40 60 80 100

All patients Darunavir FC ≤10 Darunavir FC 11-40 Darunavir FC >40 ≥1 active cPI No active cPIs HIV RNA <50 copies/mL (%)

Darunavir + RTV + OBR Control PIs

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.