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Nunes EP 1 , Oliveira MS 2 , Almeida MMTB 1 , Pilotto JH 2 , Ribeiro JE 2 , Faulhaber JC 1 , Norton M 3 , Zajdenverg R 1

Oral Presentation #TUAB0102. 48-Week Efficacy and Safety Results of Simplification to Single Agent Lopinavir/ritonavir (LPV/r) Regimen in Patients Suppressed Below 80 copies/mL on HAART - The KalMo Study.

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Nunes EP 1 , Oliveira MS 2 , Almeida MMTB 1 , Pilotto JH 2 , Ribeiro JE 2 , Faulhaber JC 1 , Norton M 3 , Zajdenverg R 1

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  1. Oral Presentation #TUAB0102 48-Week Efficacy and Safety Results of Simplification to Single Agent Lopinavir/ritonavir (LPV/r) Regimen in Patients Suppressed Below 80 copies/mL on HAART - The KalMo Study Nunes EP1, Oliveira MS2, Almeida MMTB1, Pilotto JH2, Ribeiro JE2, Faulhaber JC1, Norton M3, Zajdenverg R1, Schechter M1 1Projeto Praça Onze – UFRJ, 2Hospital Geral de Nova Iguaçu – Rio de Janeiro, Brazil; 3Abbott Laboratories, North Chicago, IL, USA

  2. KalMo: Study Design Entry criteria • HIV-1 RNA < 80 copies/mL for > 6 months • No Hx of virological failure • CD4 > 200 cells/mm3 • CD4 nadir > 100 cells/ mm3 LPV/r SGC 400/100 mg BID Mono (n= 30) N=60 Randomized 1:1Open label2 centers in Brazil 96 weeks Maintain current regimen HAART (n= 30) HIV-1 RNA measured at Week 0, 4, 12, and q12 thereafter • Primary study endpoint • Viral Load <80 copies/ml by week 48 Virological failure: confirmed HIV-1 RNA > 1,000 copies/mL Nunes EP. et al., 12th EACS, Dublin, Ireland, November 2005; PE7.5/1

  3. Demographics and Baseline Characteristics LPV/r SGC (n=30) Control(n=30) GenderMale Age (years)mean (range) Race/ethnicity Caucasian Black Other HIV-1 RNA (c/mL) CD4 count (cells/mm3)mean (range) Hepatitis C Hepatitis B 17 (54.8%) 38.6 (20-61) 10 (33%)4 (13.5%)16 (53/5%) < 80 c/mL 552.6 (232-926) 3 0 20 (69%) 40.1 (25-64) 9 (30%)5 (16.5%)16 (53.5%) < 80 c/mL 514.3 (198-1021) 1 0 Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

  4. Prior ARV Treatment * All patients were receiving 2 NRTIs ** Only 1 patient with LPV/r SGC Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

  5. Subject Disposition through 48 Weeks 60 subjects 30 subjects randomized to LPV/r monotherapy 30 subjects randomized to remain on their prior regimen 0 randomized, not dosed* 1 randomized, not dosed 29 subjects randomized and remained on prior regimen 30 subjects randomized and dosed on LPV/r monotherapy • 3 discontinuations • 1 virologic failure(w36) • 1 imprisonment (w2) • 1 pregnancy (w36) • 2 discontinuations • 1 grade 3 diarrhea • 1 pregnancy (w4) 26 continue on control regiment 28 continue on LPV/r monotherapy Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

  6. HIV-1 RNA < 80 copies/mL (ITT: NC=F) 86% 83% % with HIV-1 RNA < 80 c/mL Sample Size LPV/r monoRx Control 30 30 Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

  7. HIV-1 RNA < 80 copies/mL (OT) 96% 92% Sample Size LPV/r monoRx Control 30 30 30 28 28 28 28 28 28 28 28 26

  8. Sample Size LPV/r monoRx Control 30 30 30 28 28 28 28 28 28 28 28 26 Change in Mean CD4 Cell Count from Baseline to Week 48 (cells/mm3) 541 528 p-value = 0.799 CD4 Cell Count (cells/mm3) Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

  9. Virologic Failures and Low-level Viremia Through Week 48 LPV/r Control Patients dosed Virologic Failures (%) Week of occurence Genotype Management Outcome Low level Viremia (%) HIV-1 RNA Occurrence Outcome 30 1 (3%) 48 No Mutations d/c, add TDF+3TC < 80 c/mL after 4 wks 1 (3%) 220-850 c/mL From Wk 24 to 48 < 80 c/mL from Wk 60 to Wk 96 29 1 (3%) 36 No Mutations d/c N/A 1 (3%) 98 c/mL Once (Wk 48) < 80 cp/mL from Wk 60

  10. LPV/r monotherapy 29-Nov-04 LPV/r + TDF + 3TC11-Jan-06 Adherence (capsules count) 100% w4 95.8% w12 100% w24 97% w36 100% w48 Patient 1 – Virologic Failure 800 2000 1800 CD4 (cells/mm3) 700 WT virus Viral Load (cp/ml) 1600 600 1400 500 1200 CD4 Cell Count (cells/mm3) HIV-1 RNA (c/mL) 400 1000 800 300 600 200 400 100 200 80 c/mL 0 0 29-Nov-04 13-Dec-04 10-Jan-05 7-Mar-05 10-May-05 10-Jun-05 22-Aug-05 14-Nov-05 14-Dec-05 8-Feb-06 • Previous ARV treatment: • AZT + 3TC + IDV from April 1998 to October 2002 • AZT/3TC + LPV/r from October 2002 to 13 December 2004 • Viral load < 80 copies/mL since February 1999 Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

  11. Patient 2 – Low Level Viremia LPV/r monotherapy CD4 Cell Count (cells/mm3) 80 c/mL 16-Sep-04 14-Oct-04 1-Dec-05 2-Mar-05 25-May-05 17-Aug-05 14-Sep-05 9-Nov-05 27-Jan-06 26-Apr-06 12-Jul-06 Adherence (capsules count) 95% w4 98.9% w12 97.8% w24 99.4% w36 99.4% w48 100% w60 99% w72 98.3% w84 100% w96 • Previous ARV treatment: • AZT + ddI + RTV from September 1997 to May 2000 • AZT + ddI + IDV/r from October 2002 to December 2001 • AZT + ddI + NVP from December 2001 to September 2004 • Viral load < 80 copies/ml since April 1998 Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

  12. Adverse Events • No SAE • 99% of the events were mild to moderate Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

  13. Triglycerides (mg/dL) 261 207 P = 0.229 Sample Size LPV/r MonoRx Control 30 30 30 28 28 28 28 28 28 28 28 26 Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

  14. Cholesterol (mg/dL) Total LDL HDL Sample Size LPV/r MonoRx Control 30 30 30 28 28 28 28 28 28 28 28 26 Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

  15. Anthropomethric Measurements Waist Thigh Arms Sample Size LPV/r MonoRx Control 30 30 30 28 28 28 28 28 28 28 28 26 Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

  16. KALMO: Safety Results at Week 48 • No statistically significant differences between arms in terms of • Lipid values • Anthropometric measurements • No clinically significant laboratories abnormalities • Gastrointestinal events were more frequent in the monotherapy group (66.7% vs 16.7% of patients), specially diarrhea - 29 events in 19/30 patients (63.3%): • mild: 21 episodes • moderate: 7 episodes • severe: 1 episode (LPV/r discontinuation) • 5 treatment modifications in triple arm for drug related toxicities • 1 for intolerance to ddI • 2 for lipodystrophy • 1 for peripheral neuropathy • 1 for dyslipidemia Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

  17. Conclusions • Diarrhea was more frequent in the monotherapy group • There were 5 changes in ARV therapy due to toxicity on the control group • Rebound viremia in either arm was not associated with the selection of resistance mutations • In the one patient who failed LPV/r monotherapy, VL was re-supressed after intensification with Tenofovir + 3TC • Switching from various HAART regimens to LPV/r monotherapy, in patients who were virologically suppressed and without a history of previous virologic failure, was effective, safe and well tolerated through 48 weeks Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

  18. Acknowledgements • Projeto Praça Onze: Mauro Schechter, Estevão Portela Nunes, Mônica Merçon, Roberto Zajdenverg, Jose Claudio Faulhaber, Regina Ferro do Lago, Mônica Barbosa, Carina Yoshida, Giselly Falco, Lucimar Salgado, Roberta Millan, Marcio Fernandes, Giovanna Ianini, Cynthia Ventura • Hospital Geral de Nova Iguaçu: Marilia Santini de Oliveira, José Henrique Pilotto, Jorge Eurico Ribeiro, Lília Roy, Tânia Brum, Luciano Torres Souza, Ana Claudia Nunes Rodrigues, Andréa Gouveia, Luciane Viana • And specially the patients who participate in this study!

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