POWER 3 Study Confirms Safety and Efficacy of Darunavir/Ritonavir in Treatment-Experienced Patients Slideset on: Molina JM, Cohen C, Katlama C, et al. Safety and efficacy of darunavir (TMC114) with low- dose ritonavir in treatment-experienced patients: 24-week results of POWER 3. J Acquir Immune Defic Syndr. 2007;46: This program is supported by educational grants from Jointly sponsored by Postgraduate Institute for Medicine and Clinical Care Options, LLC

clinicaloptions.com/hiv POWER 3: Darunavir/Ritonavir in Treatment-Experienced Patients Background  Virologic and immunologic responses in treatment-experienced patients on current antiretroviral regimens inferior to those of treatment-naive patients  Darunavir/ritonavir a potent boosted PI active against wild-type and many PI-resistant viruses [1]  POWER 1 and 2 studies demonstrated efficacy and safety of darunavir/ritonavir in treatment-experienced individuals [2] –Parallel dose-ranging trials in treatment-experienced patients  Current POWER 3 study designed to provide additional data on efficacy and safety of darunavir/ritonavir 600/100 mg in treatment-experienced, HIV- infected patients [3] 1. De Meyer S, et al. Antimicrob Agents Chemother. 2005;49: Clotet B, et al. Lancet. 2007;369: Molina JM, et al. J Acquir Immune Defic Syndr. 2007;46:24-31.

clinicaloptions.com/hiv POWER 3: Darunavir/Ritonavir in Treatment-Experienced Patients Summary of Study Design  327 patients from 2 open-label phase IIb trials (TMC114-C215 conducted at 13 international sites and TMC114-C208 in Australia) –Additional data on 600/100-mg darunavir/ritonavir dose for regulatory approval –Inclusion criteria: ≥ 3 months prior NRTI use, use of ≥ 1 prior NNRTI, ≥ 1 PI-based regimen for ≥ 3 months, PI therapy for ≥ 8 weeks before screening, HIV-1 RNA > 1000 copies/mL, ≥ 1 IAS-USA primary PI mutation at screening, darunavir naive  Genotypic resistance testing performed at screening to help guide selection of optimized background regimen (OBR) comprising NRTIs ± enfuvirtide  Primary endpoint: ≥ 1 log 10 reduction in HIV-1 RNA at Week 24 (intent-to-treat, time-to-loss-of-virologic-response [ITT, TLOVR] analysis)  Secondary endpoints –HIV-1 RNA < 50 and < 400 copies/mL at Week 24 (ITT, TLOVR analysis) –Mean change in HIV-1 RNA at Week 24 (ITT, noncompleter = failure) –Mean change in CD4+ cell count at Week 24 (ITT, last observation carried forward) –Safety and tolerability Molina JM, et al. J Acquir Immune Defic Syndr. 2007;46:24-31.

clinicaloptions.com/hiv POWER 3: Darunavir/Ritonavir in Treatment-Experienced Patients Main Findings  Darunavir/ritonavir plus OBR associated with substantial virologic responses and immunologic improvement at Week 24 Molina JM, et al. J Acquir Immune Defic Syndr. 2007;46: Outcome at Week 24Patients > 1 log 10 copies/mL reduction in HIV-1 RNA, %65 HIV-1 RNA < 400 copies/mL, %57 HIV-1 RNA < 50 copies/mL, %40 Mean change in HIV-1 RNA, log 10 copies/mL-1.65 Mean change in CD4+ cell count, cells/mm 3 +80

clinicaloptions.com/hiv POWER 3: Darunavir/Ritonavir in Treatment-Experienced Patients n = Main Findings (cont’d)  Darunavir fold change ≤ 10 and HIV-1 RNA ≤ 100,000 copies/mL at baseline significantly associated with HIV-1 RNA < 50 copies/mL at Week 24 Molina JM, et al. J Acquir Immune Defic Syndr. 2007;46: HIV-1 RNA < 50 copies/mL (%) ≤ 10 > 100,000 9 > 40 ≤ 100,000 < Darunavir Fold Change HIV-1 RNA, log 10 copies/mL 50-99≥ 200 CD4+ Cell Count, cells/mm P <.0001 P =.0036 P <.0001

clinicaloptions.com/hiv POWER 3: Darunavir/Ritonavir in Treatment-Experienced Patients Other Outcomes  Most adverse events mild to moderate in severity –25% of patients reported ≥ 1 grade 3 or 4 adverse event *At Week 48. Molina JM, et al. J Acquir Immune Defic Syndr. 2007;46: Grade 3-4 Adverse Events With Incidence ≥ 2, %Darunavir/Ritonavir (n = 298) Diarrhea14 Nasopharyngitis11 Nausea10 Elevated cholesterol4 Elevated triglycerides6 Decreased white blood cell count7 Decreased lymphocytes5 Elevated pancreatic amylase7 Elevated ALT2 Elevated AST2 Neutropenia5

clinicaloptions.com/hiv POWER 3: Darunavir/Ritonavir in Treatment-Experienced Patients Summary of Key Conclusions  Darunavir/ritonavir 600/100 mg twice daily safe and effective in treatment-experienced patients with drug- resistant HIV –Rates of virologic suppression similar to those seen in POWER 1 and 2 randomized studies –Full susceptibility to darunavir strongest predictor of response –Safety profile of darunavir/ritonavir similar to that observed in POWER 1 and 2 Molina JM, et al. J Acquir Immune Defic Syndr. 2007;46:24-31.