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4th IAS Conference on HIV Pathogenesis, Treatment and Prevention Sydney, Australia, July 22-26, 2007 WEPEB117LB

4th IAS Conference on HIV Pathogenesis, Treatment and Prevention Sydney, Australia, July 22-26, 2007 WEPEB117LB.

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4th IAS Conference on HIV Pathogenesis, Treatment and Prevention Sydney, Australia, July 22-26, 2007 WEPEB117LB

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  1. 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention Sydney, Australia, July 22-26, 2007 WEPEB117LB Efficacy and safety of switching from boosted Lopinavir (LPV/r) to boosted Atazanavir (ATV/r) in patients with virologic suppression receiving a LPV/r containing HAART: The ATAZIP study Mallolas J.1, Podzamczer D.2, Domingo P.3, Clotet B.4, Ribera E.5, Gutierrez F.6, Knobel H.7, Cosin J.8, Ferrer E.2, Arranz J.A.9, Roca V.10, Vidal F.13, Murillas J.14, Pedrol E.15, Llibre J.M.16, Dalmau D.17, Garcia I.18, Aranda M.19, Pich J.11, de Lazzari E.12, Gatell J.M.1, for the ATAZIP study group 1Hospital Clinic Universitari, Infectious Diseases, Barcelona, Spain, 2Bellvitge, Infectious Diseases, Barcelona, Spain, 3Hospital Sant Pau, Medicina Interna, Barcelona, Spain, 4Fundacio IrsiCaixa, HIV, Barcelona, Spain, 5Hospital Vall d´Hebron, Infectious Diseases, Barcelona, Spain, 6Hospital de Elche, Medicine, Elche, Spain, 7Hospital del Mar, Infectious Diseases, Barcelona, Spain, 8Gregorio Marañon, Medicina, Madrid, Spain, 9Hospital Principe de Asturias, Medicina, Madrid, Spain, 10Clinico San Carlos, Medicina, Madrid, Spain, 11Hospital Clinic Universitari, Pharmacology, Barcelona, Spain, 12Hospital Clinic Universitari, Biostatistics, Barcelona, Spain 13 Hospital Joan XXIII, Tarragona 14 Hospital Son Dureta. Palma de Mallorca. 15 Hospital de Granollers. 16 Hospital de Calella.17 Mutua de Tarrasa. 18 Hospital de Hospitalet. 19 Consorci Sanitari de Tarrasa.

  2. Background • ATV is a potent, well-tolerated, once-daily (QD) protease inhibitor (PI) extensively studied in treatment-naive and -experienced patients • The SWAN study (BMS 097)1 demonstrated that switching from PI ± RTV-containing regimens to an unboosted ATV-containing regimen maintained virologic suppression with improvement in plasma lipids through 48 weeksin patients without previous failures to PI contaning regimens • However, there are limited data available on the utility of switching virologically suppressed patients from LPV/r-based regimens to a different boosted PI such as ATV/r including those with previous failures to PI containing regimens or PI associated mutations 1Gatell et al. Clin Infect Dis 2007

  3. Objective • To assess the safety and efficacy of ATV/r based HAART in virologically suppressed patients receiving a LPV/r contaning regimen including patients with previous failures (< 3) to PI regimens or history of having PI associated mutations (< 5) prior to starting the LPV/r-based regimen.

  4. Study Design Study Population (N = 265) • Stable LPV/r-based Regimen for > 6 months (VL < 200) • < 3 Previous Virologic Failures While on PI-based HAART and < 5 PI-associated mutations • The study was conducted in Spain 1:1 Randomization Switch to ATV/r QD† (N = 121) Continue LPV/r BID* (N = 127) Baseline Primary Analysis, Week 48 Final Analysis, Week 96 * LPV/r 400/100 mg BID capsules then tablets when available + unchanged NRTI backbone. † ATV/r 300/100 mg QD + unchanged NRTI backbone.

  5. Primary end-point • The proportion of patients with treatment failure for any reason through Week 48 • Includes virologic rebound (> 200 cp/mL), discontinuation of study therapy or lost to follow-up, progression to a new CDC event or death. • Non-inferiority study. Upper limit of 95% CI of estimated difference < 12.5%.

  6. Secondary end-points • The proportion of patients with virologic rebound at or prior to Week 48 • Confirmed on-study HIV RNA ≥ 200 copies/mL or last on-study HIV RNA ≥ 200 copies/mL followed by discontinuation • Time to treatment failure and to virologic failure • Safety • Evolution of fasting plasma lipids

  7. Baseline Characteristics

  8. Baseline Characteristics * P=0.023

  9. Baseline Characteristics

  10. Pacientes enrolled (n=265) Assigned to continue with LPV/r (n=127) # Assigned to switch to ATV/r (n=121) # • Continuing assigned therapy 109† (86%) • Discontinued 18 (14%) • Adverse events 6 • Death 1 * • Virological failure 1 • Lost to follow-up 6 • Patient decission 2 • Other 2 • Continuing assigned therapy 105† (86%) • Discontinued 17 (14%) • Adverse events 6 • Death 0 • Virological failure 1 • Lost to follow-up 7 • Patient decission 0 • Other 2 † 5 subjects with virological failure † 7 subjects with virological failure* Hepatic encephalopaty # 11 additional patients not eligible # 6 additional patients not eligible Patient Disposition at month 12

  11. 30 25 p = NS 20 15 10 6% 5% 5 0 6/121 8/127 Treatment Failure and Virologic Failure (≥ 200 c/mL) through month 12 Virologic Failure (≥ 200 c/mL) Treatment Failure ATV/r LPV/r p = NS 30 25 20% 20 17% 15 Proportion of patients Proportion of patients 10 5 0 21/121 25/127 Difference Estimate (95% CI) -2.3% (–12%, 8%) –1.3% (–7.7%, 4.8%)

  12. Time to treatment failure

  13. Time to virological failure P=0.5 P=0.5 p=0.609, long rank test

  14. Virological failures through month 12 ATV/r (n=121) LPV/r (127) N 6 8 Previous PI failures 2 4 Previous PI mutations 6 1 Previous PI major mutations 2 1 High baseline risk (*) 5 5 Reported lack of adherence 0 4 Continue with same cART 5 7 Virological response at 12 mo. 3 4 * Previous >= 1 PI failure or >= 3 PI mutations or >= 1 major PI mutation

  15. CD4 Changes • Median changes from baseline in CD4 cell count were similar beteween groups: +26 cells/mm3 (ATV/r) and +51 cells/mm3 (LPV/r) at month 12 (p=0.2)

  16. Adverse Events through month 12. * Hepatic encephalopaty; # ALT 113, AST 90

  17. LAB Abnormalities

  18. Fasting LIPIDS. Median values and Changes From Baseline in Lipid Parametersat month 12

  19. LIPIDS. Percentage above NCEP treatment recommendations at baseline and through month 12.

  20. Conclusions • Switching to ATV/r in virologically suppressed patients who were receiving a LPV/r containing HAART provided comparable efficacy and safety profile with improved lipid parameters.

  21. ATAZIP Study Group HOSPITAL BELLVITGE HOSPITALET D. Podzamczer E. Ferrer G. Leibenger HOSPITAL SANT PAU BARCELONA P. Domingo M. Gutiérrezerrer G. Mateo HOSPITAL GERMANS TRIAS I PUJOL BADALONA B. Clotet P. Echeverria C. Alcalde HOSPITAL CLINIC BARCELONA J. Mallolas J.M. Gatell J. Pich E. de Lazzari E. Martínez A. Milinkovic A. Cruceta H. Agell J.A. Arnaiz HOSPITAL VALL D’HEBRÓN BARCELONA E. Ribera S. Villar HOSPITAL ELCHE ALICANTE F. Gutiérrez M. Masiá E. Bernal HOSPITAL MAR BARCELONA H. Knobel A. González G. Mestre HOSPITAL GREGORIO MARAÑÓN MADRID J. Cosín M. Sánchez M. Ramírez I. Gutiérrez HOSPITAL PRINCIPE ASTURIAS MADRID J.A. Arranz J. Sanz E. Casas HOSPITAL CLÍNICO SAN CARLOS MADRID V. Roca J. Vergas M.J. Téllez HOSPITAL JOAN XXIII TARRAGONA F. Vidal J. Peraire M. Saumoy HOSPITAL SON DURETA PALMA MALLORCA M. Peñaranda J. Murillas HOSPITAL GRANOLLERS GRANOLLERS E. Pedrol E. Deig HOSPITAL CALELLA CALELLA J.M. Llibre S. Valero HOSPITAL MUTUA TERRASSA TERRASSA D. Dalmau M. Cairó HOSPITAL L’HOSPITALET HOSPITALET I. García HOSPITAL TERRASSA TERRASSA M. Aranda

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