48Week Efficacy and Safety Results of Simplification to Single Agent Lopinavirritonavir LPVr Regimen

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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 HAART - The KalMo Study
Oral Presentation TUAB0102

• 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

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KalMo Study Design

• Entry criteria
• HIV-1 RNA lt 80 copies/mL for gt 6 months
• No Hx of virological failure
• CD4 gt 200 cells/mm3
• CD4 nadir gt 100 cells/ mm3

LPV/r SGC 400/100 mg BID Mono (n 30)
N60 Randomized 11Open 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 lt80 copies/ml by week 48
• Virological failure confirmed HIV-1 RNA gt 1,000
  copies/mL

Nunes EP. et al., 12th EACS, Dublin, Ireland,
November 2005 PE7.5/1
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Demographics and Baseline Characteristics
LPV/r SGC (n30)
Control(n30)
Gender Male Age (years) mean
(range) Race/ethnicity Caucasian
Black Other HIV-1 RNA (c/mL) CD4
count (cells/mm3) mean (range) Hepatitis
C Hepatitis B
20 (69) 40.1 (25-64 ) 9 (30)5 (16.5)16
(53.5) lt 80 c/mL 514.3 (198-1021) 1 0
17 (54.8) 38.6 (20-61) 10 (33)4 (13.5)16
(53/5) lt 80 c/mL 552.6 (232-926) 3 0
Nunes EP. et al., XVI IAC,Toronto, Canada, 2006
TUAB0102
KalMo
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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
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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
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HIV-1 RNA lt 80 copies/mL (ITT NCF)
86
83
with HIV-1 RNA lt 80 c/mL
Sample Size LPV/r monoRx Control
30 30
Nunes EP. et al., XVI IAC,Toronto, Canada, 2006
TUAB0102
KalMo
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HIV-1 RNA lt 80 copies/mL (OT)
96
92
Sample Size LPV/r monoRx Control
30 30
30 28
28 28
28 28
28 28
28 26
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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
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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 TDF3TC lt 80
c/mL after 4 wks 1 (3) 220-850 c/mL From Wk 24
to 48 lt 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) lt 80 cp/mL from Wk 60
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Patient 1 Virologic Failure
LPV/r monotherapy 29-Nov-04
LPV/r TDF 3TC11-Jan-06
WT virus
CD4 Cell Count (cells/mm3)
80 c/mL
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
Adherence (capsules count)
100 w4
95.8 w12
100 w24
97 w36
100 w48

• 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 lt 80 copies/mL since February 1999

Nunes EP. et al., XVI IAC,Toronto, Canada, 2006
TUAB0102
KalMo
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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 lt 80 copies/ml since April 1998

Nunes EP. et al., XVI IAC,Toronto, Canada, 2006
TUAB0102
KalMo
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Adverse Events

• No SAE
• 99 of the events were mild to moderate

Nunes EP. et al., XVI IAC,Toronto, Canada, 2006
TUAB0102
KalMo
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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
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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
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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
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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
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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
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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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