ATV RTV versus ATV SQV versus LPVRTV AI

ATV + RTV versus ATV + SQV versus LPV-RTV AI 424 -045 Study

ATV + RTV versus ATV + SQV versus LPV-RTV AI 424 -045: Study Design: AI 424 -045 Study • Background: Randomized, open label trial in patients with prior treatment failure evaluating efficacy and safety of ritonavirboosted atazanavir versus atazanavir plus saquinavir versus both in comparison with lopinavir-ritonavir, all given with 2 NRTIs • Inclusion Criteria (n = 358) - Age > 16 - History of ≥ 2 failures on regimens containing > 1 NRTI, a NNRTI, and a PI - CD 4 > 50 cells/mm 3 - HIV RNA >1, 000 copies/m. L • Treatment Arms - ATV mg 300 + RTV 100 mg + 2 NRTIs* - ATV 400 mg + SQV 1200 mg + 2 NRTIs* - LPV/r 400/100 mg BID + 2 NRTIs* Source: Johnson M, et al. AIDS. 2005; 19: 685 -94. Atazanavir + Ritonavir + 2 NRTIs* (n = 120) Atazanavir + Saquinavir + 2 NRTIs* (n = 115) Lopinavir-ritonavir + 2 NRTIs* (n= 123) *2 NRTIs = Tenofovir DF + 2 nd NRTI

ATV + RTV versus ATV + SQV versus LPV-RTV AI 424 -045: Results HIV RNA <50 copies/ml (%) Week 48: Virologic Response (ITT), by Number of Baseline PI Mutations 100 ATV + RTV + 2 NRTIs ATV + SQV + 2 NRTIs LPV-RTV + 2 NRTIs 80 55 60 46 40 38 44 38 26 30 25 20 3 0 Overall < 4 PI mutations ≥ 4 PI mutations Number of PI-Associated Mutations Source: Johnson M, et al. AIDS. 2005; 19: 685 -94.

ATV + RTV versus ATV + SQV versus LPV-RTV AI 424 -045: Results Week 48: Changes in Lipid Concentrations ATV + RTV + 2 NRTIs ATV + SQV + 2 NRTIs LPV-RTV + 2 NRTIs Mean Change from Baseline (%) 40 30 30 20 6 10 4 2 1 0 -10 -8 -4 -3 -7 -10 -20 -4 -14 -30 -40 Total Cholesterol HDL Source: Johnson M, et al. AIDS. 2005; 19: 685 -94. Fasting LDL Fasting Triglycerides

ATV + RTV versus ATV + SQV versus LPV-RTV AI 424 -045: Conclusions: “ATV boosted with RTV is as effective and well tolerated as LPV/RTV in treatment-experienced patients, with a more favorable impact on serum lipids. Pharmacokinetically enhanced ATV provides a suitable choice for therapy of treatment-experienced HIV-infected patients. ” Source: Johnson M, et al. AIDS. 2005; 19: 685 -94.

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.