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48-Week Efficacy and Safety Results of Simplification to Single Agent Lopinavir/ritonavir (LPV/r) Regimen in Patients Suppressed Below 80 copies/mL on.

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Presentation on theme: "48-Week Efficacy and Safety Results of Simplification to Single Agent Lopinavir/ritonavir (LPV/r) Regimen in Patients Suppressed Below 80 copies/mL on."— Presentation transcript:

1 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 EP 1, Oliveira MS 2, Almeida MMTB 1, Pilotto JH 2, Ribeiro JE 2, Faulhaber JC 1, Norton M 3, Zajdenverg R 1, Schechter M 1 1 Projeto Praça Onze – UFRJ, 2 Hospital Geral de Nova Iguaçu – Rio de Janeiro, Brazil; 3 Abbott Laboratories, North Chicago, IL, USA Oral Presentation #TUAB0102

2 KalMo: Study Design Nunes EP. et al., 12 th EACS, Dublin, Ireland, November 2005; PE7.5/1 Entry criteria   HIV-1 RNA 6 months   No Hx of virological failure   CD4 > 200 cells/mm 3   CD4 nadir > 100 cells/ mm 3 Primary study endpoint   Viral Load <80 copies/ml by week 48 Virological failure: confirmed HIV-1 RNA > 1,000 copies/mL 96 weeks LPV/r SGC 400/100 mg BID Mono (n = 30) Maintain current regimen HAART (n = 30) N=60 Randomized 1:1 Open label 2 centers in Brazil HIV-1 RNA measured at Week 0, 4, 12, and q12 thereafter

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

4 Prior ARV Treatment Prior Treatment *LPV/r SGC (n = 30) Control (n = 30) Mean Time (months) Time (range - months)12 to 8410 to 101 Protease Inhibitors (PI) **10 (33.3%)9 (30%) Non-nucleosides (NNRTI)19 (63.3%) PI + NNRTI0 (0%)2 (6.7%) 3 nucleoside analogues1 (3.4%)0 (0%) * 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 29 subjects randomized and remained on prior regimen 30 subjects randomized and dosed on LPV/r monotherapy 2 discontinuations 1 grade 3 diarrhea 1 pregnancy (w4) 3 discontinuations 1 virologic failure (w36) 1 imprisonment (w2) 1 pregnancy (w36) 28 continue on LPV/r monotherapy 26 continue on control regiment 0 randomized, not dosed* 30 subjects randomized to LPV/r monotherapy 30 subjects randomized to remain on their prior regimen 1 randomized, not dosed Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

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

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

8 Change in Mean CD4 Cell Count from Baseline to Week 48 (cells/mm 3 ) p-value = Sample Size LPV/r monoRx Control CD4 Cell Count (cells/mm 3 ) Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

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

10 Previous ARV treatment: AZT + 3TC + IDV from April 1998 to October 2002 AZT + 3TC + IDV from April 1998 to October 2002 AZT/3TC + LPV/r from October 2002 to 13 December 2004 AZT/3TC + LPV/r from October 2002 to 13 December 2004 Viral load < 80 copies/mL since February 1999 LPV/r monotherapy 29-Nov-04 LPV/r + TDF + 3TC 11-Jan-06 Adherence Adherence (capsules count) 100%w495.8%w12100%w2497%w36100%w48 Patient 1 – Virologic Failure 29-Nov Dec Jan-05 7-Mar May Jun Aug Nov Dec-05 8-Feb Nov Dec Jan-05 7-Mar May Jun Aug Nov Dec-05 8-Feb c/mL CD4 Cell Count (cells/mm 3 ) Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo WT virus HIV-1 RNA (c/mL) CD4 (cells/mm3) Viral Load (cp/ml)

11 Previous ARV treatment: AZT + ddI + RTV from September 1997 to May 2000 AZT + ddI + RTV from September 1997 to May 2000 AZT + ddI + IDV/r from October 2002 to December 2001 AZT + ddI + IDV/r from October 2002 to December 2001 AZT + ddI + NVP from December 2001 to September 2004 AZT + ddI + NVP from December 2001 to September 2004 Viral load < 80 copies/ml since April 1998 Patient 2 – Low Level Viremia LPV/r monotherapy Adherence (capsules count) 95%w498.9%w1297.8%w2499.4%w3699.4%w48100%w6099%w7298.3%w84100%w96 16-Sep Oct-04 1-Dec-05 2-Mar May Aug Sep-05 9-Nov Jan Apr Jul-06 CD4 Cell Count (cells/mm 3 ) 80 c/mL Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

12 Adverse Events LPV/r SGC Control No of AE (%) AE = 103 No of patients (%) n = 30 No of AE (%) AE = 96 No of patients (%) n = 30 Infection 36 (35%)22 (73.3%)44 (45.8%)24 (80%) Skin 3 (3%)3 (10%)10 (10.4%)6 (20%) Pain 17 (16.5%)12 (40%)15 (15.6%)11 (36.7%) Gastrointestinal 39 (37.9%)20 (66.7%)8 (8.3%)5 (16.7%) Diarrhea * 29 (28.1%)19 (63.3%)2 (2.1%)2 (6.7%) Others 8 (7.8%)7 (23.4%)19 (10.8%)13 (43.3%) No SAE No SAE 99% of the events were mild to moderate 99% of the events were mild to moderate Nunes EP. et al., XVI IAC,Toronto, Canada, 2006; #TUAB0102 KalMo

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

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

15 Waist Thigh Arms Anthropomethric Measurements Sample Size LPV/r MonoRx Control 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 29 events in 19/30 patients (63.3%): 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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