ABC3TCN176 165 168 - PowerPoint PPT Presentation

Title: ABC3TCN176 165 168


1
SIMPLIFICATION WITH FIXED-DOSE TENOFOVIR-EMTRICITA
INE OR ABACAVIR-LAMIVUDINE IN ADULTS WITH
SUPPRESSED HIV REPLICATION (THE STEAL STUDY)
A RANDOMIZED, OPEN-LABEL, 96-WEEK,
NON-INFERIORITY TRIAL
Poster 576
FACULTY OF MEDICINE THE UNIVERSITY OF NEW SOUTH W
ALES Level 2, 376 Victoria St Darlinghurst NSW,
2010 Australia Telephone 61 (2) 8382 3707 Facs
imile 61 (2) 8382 2090 Email acarr_at_stvincents
.com.au www.med.unsw.edu.au/nchecr
David A Cooper1, Mark Bloch2, Allison Humphries1,
Janaki Amin1, David Baker3, Sean Emery1, Andrew
Carr4 on behalf of the STEAL study group
1National Centre in HIV Epidemiology and Clinica
l Research, University of New South Wales
2Holdsworth House Medical Practice 3East Sydney
Doctors 4St Vincents Hospital, Sydney, NSW,
Australia
Introduction
Results

• Two once-daily, dual nucleoside analogue,
  reverse transcriptase inhibitor (NRTI),
  fixed-dose-combination (FDC) tablets available
  
• tenofovir 300mg-emtricitabine 200mg (TDF-FTC)
• abacavir 600mg-lamivudine 300mg (ABC-3TC)
• Which FDC is more effective and safe is
  uncertain.
  
• We hypothesized that switching to TDF-FTC would
  be virologically non-inferior to ABC-3TC over 96
  weeks in HIV-infected adults with sustained
  suppression of HIV replication, but that TDF-FTC
  and ABC-3TC would have different safety profiles.

Assessed for eligibility 441
Not randomized 81 Ineligible 70 HLA-B5701-po
sitive 26 HIV RNA 50 copies/ml plasma 19 eG
FR 8 antiretroviral contra-indication 2 crea
tinine clearance prior abacavir hypersensitivity 1
unboosted atazanavir 1 Eligible 11 patient
choice 9 physician choice 1 exceeded sc
reening period 1
Figure 2 TotalHDL cholesterol
Figure 3 Calendar period at commencement of
lipid-lowering therapy
P0.025
Pns
Change
Randomized 360
Methods
96
Allocated ABC-3TC 180 Participant withdrew 1

ABC-3TC N175
162 158
TDF-FTC N174
168 164
Allocated TDF-FTC 180 Participant withdrew 2

• Eligible participants randomly allocated 11 to
  continue their current NNRTI and/or PI and switch
  their NRTIs to either TDF-FTC or ABC-3TC.
  
• Key eligibility criteria
• Age 18 years
• on stable 2NRTI NNRTI or PI ART 12 weeks
• HIV RNA
• glomerular filtration rate (GFR)
  70mL/min/1.73m2
  
• creatinine clearance 50 mL/min
• HLA-B5701 negative (unless already on ABC)
• no prior hypersensitivity, intolerance or
  failure to study drugs
  
• no prior exposure to either study FDC drugs
• not on un-boosted atazanavir
• no previous non-traumatic fracture
• Study visits at 0, 4, 12, 24, 36, 48, 60, 72,
  84 and 96 weeks.
  
• At each visit adverse events, concomitant
  medications, adherence, weight, biochemistry and
  HIV viral load were assessed every 12 weeks
  blood count, liver function tests and CD4 count
  performed and blood stored every 24 weeks
  quality of life (SF-8) and fasting metabolic
  measures conducted every 48 weeks body
  composition measured by dual-energy x-ray
  absorptiometry
• Primary endpoint was virological failure,
  defined by repeat viral load 400 copies/mL by
  intention-to-treat, missingfailure (ITTMF)
  analysis. Secondary endpoints (ITT) included
  death, AIDS, serious non-AIDS events, metabolic
  parameters and body composition
  (bone/soft-tissue ITT-LOCF).
• Exact statistics were used for differences in
  proportions, T-tests to compare means and Cox
  regression for hazard ratios. A sample of 175
  participants per group yielded a 90 probability
  to detect a two-tailed 95 confidence interval of
  15 around a 0 difference between treatment arms
  in virological failure rates.

Changes in Bone Mineral Density
Received ABC 179 Ceased ABC-3TC 25 adverse
event 12 lost to follow-up 4 patient c
hoice 3 died 3 cardiac risk 1
other 2
Received TDF-FTC 178 Ceased TDF-FTC 19 adver
se event 8 lost to follow-up 2 patie
nt choice 3 died 1 virological failu
re 1 other 4
Right hip t-score
Spine t-score
P
P
P0.002
P0.023
Change
Analysed 179
Analysed 178
This association remained significant when adj
usted for baseline smoking or time on randomized
ART
Table 1 Baseline participant characteristics
TDF-FTC
ABC-3TC
Demographics
44 8
46 9
Age (years)
ABC-3TC N176 165 168
TDF-FTC N176 167 172
N175 164
167 N176 167
172
98
97
Male ()
86
86
White ethnicity ()
25 4
25 3
BMI (kg/m2)
Conclusion
HIV History
89
88
MSM transmission ()
16
17
Prior AIDS ()

• In this population, TDF-FTC and ABC-3TC had
  similar virological efficacy.
  
• However, ABC-3TC was associated with more SNAEs
  (particularly cardiovascular disease) and lipid
  endpoints, and TDF-FTC caused more BMD loss.

10 6
10 6
HIV duration (years)
599 257
627 306
CD4 count (cells/mm3)
Non-HIV History
11
13
Hypertension ()
2
4
Ischaemic heart disease ()
1
0
Ischaemic stroke ()
STEAL Protocol Steering Committee Janaki Amin,
David Baker, Mark Bloch, Andrew Carr, David
Cooper, Sean Emery, Allison Humphries
STEAL study investigators Mark Bloch, David
Cooper, Andrew Carr, David Baker, Robert
Finlayson, Jennifer Hoy, Tim Read, Nicholas
Doong, Norman Roth, Jonathan Anderson, Richard
Moore, John Chuah, Alan Street, David Shaw, David
Orth, Mark Kelly, David Smith, David Nolan, Mark
Boyd, David Gordon, Nicholas Medland, Ban Kiem
Tee, Dominic Dwyer, John Dyer, Ian Woolley,
Michelle Giles, Stephen Davies, Linda Dayan,
William Donohue, Darren Russell, Jeffrey Post,
John Quinn, Don Smith, Anthony Allworth.
Acknowledgements
29
40
Current smoker ()
5
3
Diabetes mellitus ()
STEAL study coordinators Shikha Agrawal, Kate
Beileiter, Karen Macrae, Richard Norris, Robert
Fielden, Robyn Vale, Robyn Richardson, Sophie
Dinning, Isabel Prone, Christine Alveras, Rachel
Liddle, Julie Silvers, Helen Kent, Jeff Hudson,
Helen Lau, Kaye Lowe, Paul Cortissos, Sian
Edwards, Denise Lester, Tammy Schmidt, Fiona
Clark, Janine Roney, Lyndal Daly, David Youds,
Paul Negus, Peita-Lee Ambrose, Denni Pearson,
Cherie Mincham, Claire Forsdyke, Robyn Gilligan,
Michelle Wall, Rachel Wundke, Maggie Piper,
Jacqueline Kerth, Samantha Libertino, Pauline
Galt, James Baber, Victoria Hounsfield, Michael
Curry, Joy Oddy, Christine Remington, Laura Foy,
Debra Hayhoe, Bernie Monaghan, Nicky Cunningham,
Suzanne Ryan, Helen Best, Catherine Magill, Jason
Gao, Jega Sarangapany, Janelle Zillman, Anne
Sleat, Holly Asher STEAL study team Sean Emery,
Allison Humphries, Janaki Amin, Wilma Goodyear,
Kymme Courtney-Vega, Simone Jacoby, Hila
Haskelberg, Cate Carey, Allie MacDonald, Lina
Safro, Maja Berilazic, Aurelio Vulcao, David
Courtney-Rodgers, Maria Arriaga, Tian Erho, Kat
Marks, Kate Merlin, Julie Yeung
STEAL DSMB members Dr Alan Winston, Prof Steve
Wesselingh, Dr Deborah Black STEAL Independent
SNAE Reviewer Dr Gail Matthews
We extend our grateful thanks to all the
participants and the Victorian Red Cross Blood
Bank for HLA-B5701 testing NCHECR is funded by t
he Australian Government Department of Health
Ageing and is affiliated with the Faculty of
Medicine, The University of New South Wales.
7 5
8 7
Framingham CVD risk ()
Antiretroviral Therapy
21
20
ABC ()
30
30
TDF ()
HCV ve
23
24
Protease Inhibitor ()