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XV Congreso Panamericano De Infectología • Punta del Este, Uruguay 7-11 April 2011

Lopinavir/ritonavir (LPV/r) Combined with Raltegravir (RAL) or Tenofovir/Emtricitabine (TDF/FTC) in Antiretroviral-Naïve Subjects: 96-Week Efficacy and Safety Results of the PROGRESS Study.

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XV Congreso Panamericano De Infectología • Punta del Este, Uruguay 7-11 April 2011

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  1. Lopinavir/ritonavir (LPV/r) Combined with Raltegravir (RAL) or Tenofovir/Emtricitabine (TDF/FTC) in Antiretroviral-Naïve Subjects: 96-Week Efficacy and Safety Results of the PROGRESS Study Ruth Soto-Malave1Adebayo Lawal2 Jacques Reynes3, Federico Pulido4, Joseph Gathe5, Min Tian2, Linda Fredrick2, Thomas Podsadecki2, Angela Nilius2 1.University of Puerto Rico, School of Medicine, Infectious Diseases Section, San Juan, Puerto Rico and Innovative Care PSC, Bayamon, Puerto Rico 2. Abbott, Abbott Park, Illinois 3. Department of Infectious and Tropical Diseases, Montpellier University Hospital, Montpellier, France 4. Unidad VIH. Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain 5.Therapeutic Concepts, Houston, Texas XV Congreso Panamericano De Infectología •Punta del Este, Uruguay 7-11 April 2011

  2. Background • Standard therapy for HIV-1 infected, antiretroviral-naïve patients, consists of a Protease Inhibitor (PI), Non-Nucleoside Reverse Transcriptase Inhibitor, Integrase Strand Transfer Inhibitor, or CCR5 Inhibitor + 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) • For those whom NRTI-containing combinations may not be the best option, a NRTI-sparing regimen may offer an alternative therapeutic approach • The SPARTAN study and the ACTG 5262 study have recently raised questions over the safety and efficacy of ATV+RAL and DRV+ritonavir+RAL, respectively • The PROGRESS trial is the first study designed to test the efficacy and safety of LPV/r and RAL in antiretroviral-naïve subjects

  3. LPV/r + RAL vs. LPV/r + TDF/FTC in Treatment-Naive Subjects: PROGRESS Study Design* • Inclusion Criteria for PROGRESS (M10-336) • HIV-1 infection • ARV-naïve • Plasma HIV-1 RNA >1000 copies/mL • Any CD4+ T-cell count LPV/r 400/100 mg BID + RAL 400 mg BID (n=101) Week 48 Primary Efficacy Endpoint Screening Week 96 LPV/r 400/100 mg BID + TDF/FTC 300/200 mg QD (n=105) • Met Primary Endpoint of Noninferiority • Primary endpoint: plasma HIV-1 RNA <40 copies/mL at week 48 (FDA-TLOVR) • FDA-TLOVR week 48: LPV/r + RAL=83.2%, LPV/r + TDF/FTC=84.8% • P=0.850, difference -1.6%, 95% exact confidence interval (CI) -12.0%, 8.8% • Safety and tolerability were similar at week 48 * 3 subjects were randomized but not dosed

  4. Baseline Demographics and HIV Disease Characteristics * Plasma HIV-1 viral loads determined using automated, quantitative RT-PCR assay (Abbott RealTime HIV-1 assay® ) Groups were compared using one-way ANOVA for continuous variables and Fisher’s exact test for categorical variables.

  5. Subject Disposition at Week 96 * P>0.05 for LPV/r +RAL vs. LPV/r + TDF/FTC comparison for each reason based on Fisher's exact test † 1 LPV/r + RAL subject discontinued for two reasons: Noncompliance and Other

  6. Proportion of Subjects Responding at Week 96 (FDA-TLOVR)

  7. Proportion of Subjects Responding at Week 96 (Observed Data Analysis)

  8. Mean CD4+ T-cell Counts Through 96 Weeks of Treatment (Cells/mm3)

  9. Number and % of Subjects with Moderate or Severe Drug-Related Adverse Events* * Occurring in ≥2.0% in either treatment group † Hypercholesterolaemia includes blood cholesterol increased, hypertriglyceridaemia includes blood triglycerides increased P>0.05 for LPV/r + RAL vs. LPV/r + TDF/FTC comparison for each adverse event based on Fisher's exact test

  10. Number and % of Subjects with Grade 3+ Laboratory Values* * Occurring in ≥2.0% in either treatment group † P<0.05 for LPV/r + RAL vs. LPV/r + TDF/FTC comparison based on Fisher's exact test

  11. Mean change in Lipid Levels at Week 96 P>0.05 for difference between treatment groups in mean change at all time points using one-way ANOVA

  12. Emergence of Resistance-Associated Mutations (RAMs)* Through 96 Weeks 13 subjects (8 LPV/r + RAL and 5 LPV/r + TDF/FTC) met the protocol-defined criteria for resistance testing • FTC RAM was detected in 1 subject (week 40) • RAL RAMs without LPV/r RAMs were detected in 2 subjects (weeks 48 and 65) • RAL (week 16) and LPV/r (week 72) RAMs were detected in 1 subject * Resistance was specified by the 2010 IAS-USA panel.

  13. Adherence via MEMS Data: 96 Weeks Adherence was similar between treatment groups regardless of adherence measure P>0.100 for each measure based on Wilcoxon rank sum test to test for differences between groups in the distribution of subjects’ adherence rates

  14. Conclusions at 96 Weeks • LPV/r + RAL virologic efficacy was comparable to LPV/r + TDF/FTC • Proportion of subjects responding [FDA-TLOVR, P=0.767] • LPV/r + RAL: 66.3% • LPV/r + TDF/FTC: 68.6% • Similar mean increases in CD4+ T-cell counts at week 96 (P=0.598) • LPV/r + RAL: +281.0 cells/mm3 • LPV/r + TDF/FTC: +296.4 cells/mm3 • Both regimens were generally well tolerated with few study drug-related discontinuations • Discontinuations for AEs or HIV-related events: LPV/r + RAL=5.0% and LPV/r + TDF/FTC=3.8% • AE profile and laboratory abnormalities were generally similar with the exception of percent of subjects with CPK elevations: LPV/r + RAL=19.8% and LPV/r + TDF/FTC=8.7%

  15. PROGRESS: Acknowledgements • The authors express their gratitude • To the subjects and their families for their participation and support during the study, the PROGRESS (M10-336) Study Team at Abbott, the clinical research personnel who worked on this study, Merck for providing raltegravir, and Sarah Kopecky-Bromberg (Abbott) for medical writing support • To the PROGRESS investigators: Canada Dr. Jonathan B. Angel Dr. François Laplante Dr. Mona Loutfy Dr. Anita Rachilis France Dr. Laurent Cotte Dr. Pierre-Marie Girard Dr. Jacques Reynes Dr. Dominique Salmon-Ceron Puerto Rico Dr. Ivan Melendez-Rivera Dr. Ruth Soto-Malave Italy Dr. Franco Baldelli Dr. Antonio Di Biagio Dr. Fiorella Di Sora Dr. Adriano Lazzarin Dr. Claudio Viscoli Spain Dr. Jose R. Arribas Dr. Bonaventura Clotet Dr. Pere Domingo Dr. Daniel Podzamczer Dr. Federico Pulido Dr. Jesús Sanz Dr. Pompeyo Viciana USA Dr. Laveeza Bhatti Dr. Larry M. Bush Dr. Frederick A. Cruickshank Dr. Edwin DeJesus Dr. Robin H. Dretler Dr. Joseph Gathe Dr. Cynthia A. Mayer Dr. Lewis McCurdy Dr. Ighovwerha Ofotokun Dr. Gerald Pierone Jr. Dr. Moti Ramgopal Dr. Louis M. Sloan Dr. Lawrence F. Waldman Poland Dr. Brygida Knysz

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