SWIFT Study: Swi tching F rom Lamivudine/Abacavir (3TC/ABC) to Emtricitabine/ T enofovir DF (FTC/TDF) . R Campo 1 , E DeJesus 2 , H Khanlou 3 , H Wang 4 , K White 4 , L Dau 4 , J Flaherty 4 , and T Fralich 4 1 Univ of Miami Sch of Med, Miami, FL, USA; - PowerPoint PPT Presentation
1 SWIFT Study: Swi tching F rom Lamivudine/Abacavir (3TC/ABC) to Emtricitabine/T enofovir DF (FTC/TDF) R Campo 1 , E DeJesus 2 , H Khanlou 3 , H Wang 4 , K White 4 , L Dau 4 , J Flaherty 4 , and T Fralich 4 1 Univ of Miami Sch of Med, Miami, FL, USA; 2 Orlando Immunology Ctr, Orlando, FL, USA; 3 AIDS Healthcare Foundation, Los Angeles, CA, USA; 4 Gilead Sciences, Inc., Foster City, CA, USA 6 th IAS Conference on HIV Pathogenesis, Treatment and Prevention July 17-20, 2011, Rome, Italy Oral Presentation WELBB03 Study GS-164-0216
Transcript
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SWIFT Study: Switching From Lamivudine/Abacavir (3TC/ABC)
to Emtricitabine/Tenofovir DF (FTC/TDF)
R Campo1, E DeJesus2, H Khanlou3, H Wang4, K White4, L Dau4, J Flaherty4, and T Fralich4
1Univ of Miami Sch of Med, Miami, FL, USA;2Orlando Immunology Ctr, Orlando, FL, USA;
3AIDS Healthcare Foundation, Los Angeles, CA, USA;4Gilead Sciences, Inc., Foster City, CA, USA
6th IAS Conference on HIV Pathogenesis, Treatment and PreventionJuly 17-20, 2011, Rome, ItalyOral Presentation WELBB03
5. D:A:D Study Group, Lancet, 20086. Saxs, 5202, NEJM, 20097. Martinez E, et al. BICOMBO, IAS 20078. Moyle G, et al. ROCKET I, HIV10 2010
• DHHS and IAS-USA Guidelines1 list FTC/TDF as the “preferred” NRTI backbone and 3TC/ABC as an alternative backbone– The DHHS Committee based its recommendations on ACTG 52022, ASSERT3,
hypersensitivity reactions (HSR) to 3TC/ABC4, D:A:D Cohort5
• EACS Guidelines list both FTC/TDF and 3TC/ABC as recommended and when using ABC, states the need for HLA-B*5701 testing and caution in persons with higher risk of CV disease and baseline high viral load6
• BICOMBO showed less virologic failures7 at week 48 and ROCKET I demonstrated lipid benefits8 in subjects on FTC/TDF compared to 3TC/ABC
• These Guidelines and published studies may prompt clinicians to consider switching virologically stable patients from 3TC/ABC to FTC/TDF
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Prospective, open-label, multicenter, randomized, Phase 4, 48-week study conducted in Canada, Puerto Rico, and the United States
FTC/TDF + PI/rn=155
3TC/ABC + PI/rn=156
48 weeks
Ran
dom
ized
1:13TC/ABC +PI/r
for ≥3 monthsHIV RNA < 200c/mL ≥ 3 months
N = 311 randomized and treated
SWIFTStudy Design
No prior history of resistance to study drugs No CD4 restrictionStratified by PI: 32% LPV/r vs. 68% Non-LPV/r
Primary Endpoint• Proportion of subjects with HIV‑1 RNA 200 copies/mL through Week 48
based on TLOVR (virologic failure*, premature discontinuation for any reason, ARV modifications = TLOVR failure)
• The FTC/TDF arm would be declared non-inferior to the 3TC/ABC arm if the lower bound of the 95% CI was greater than −12%
Secondary Endpoints• Proportion who experienced virologic failure through Week 48• Safety and tolerability through 48 weeks • Change from baseline in GFR by Cockcroft Gault and MDRD• Change from baseline in fasting lipid parameters (TC, LDL, HDL, TG,
and TC/HDL ratio) through 48 weeks
Study Endpoints
*Virologic failure pre-defined as confirmed HIV RNA > threshold, or last on-study > threshold, with the thresholds of HIV‑1 RNA at 200 copies/mL
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Characteristic FTC/TDFn=155
3TC/ABCn=156
Age, median (IQR), years 46 (40, 52) 46 (41, 53)Male gender, n (%) 129 (83) 134 (86)Race, n (%) White 96 (62) 106 (68) African American 43 (28) 44 (28)HIV RNA c/mL, n (%) <50 139 (90) 145 (93) 50 to < 200 13 (8) 10 (6) 200 to < 400 2 (1) 1 (1) > 400 1 (1) 0Time since first ARV therapy, median (IQR), years 4 (2.5, 6.9) 3.7 (2.5, 6.7)CD4 cell count, median (IQR), cells/mm3 532 (354, 725) 532 (382, 728)Lipid modifying agent, n (%) 67 (43) 80 (51)
Baseline Characteristics
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Subject Disposition through Week 48
Subject Randomized N=312*
Subject Treated N=311†
FTC/TDFn=155n (%)
3TC/ABC n=156 n (%)
Completed 48 weeks of study 138 (89%) 139 (89%)
Discontinued study prematurely 17 (11%) 17 (11%)
Adverse events 7 3 Pregnancy 0 1 Lack of efficacy 0 1 Withdrew consent 5 4 Lost to follow-up 4 5 Investigator discretion 0 3 Protocol violation 1 0
*1 subject randomized to FTC/TDF and not treated† As treated (n=311) for safety analysis; ITT (n=310) for efficacy analysis (as 1subject in the FTC/TDF had major protocol
violation with baseline resistance to study drug)
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Primary Endpoint: TLOVR Responders with HIV-1 RNA <200 c/mL through Week 48
86% 83%
0%
20%
40%
60%
80%
100%
FTC/TDF 3TC/ABC
% T
LOVR
Res
pond
ers
HIV
-1 R
NA
< 20
0c/m
L
-5.1 3.0 11.2
-12 0 12
95% CI for difference (FTC/TDF- 3TC/ABC)
% Difference TLOVR Responder Rate
Favors FTC/TDF ◄ Favors 3TC/ABC
3
11
0
5
10
15
FTC/TDF 3TC/ABC
# Su
bjec
ts w
ith V
irolo
gic
Failu
re
*VF is estimated by Kaplan Meier product limit method and log-Rank test is used for detecting treatment differences through Week 48
Virologic Failure* (HIV-1 RNA 200 c/mL) through Week 48
p=0.034 • 3TC/ABC VFs (n=11)– 8 No genotypes performed (VL<1,000 c/mL)– 3 Genotypes (no resistance to study drug)
• FTC/TDF VFs (n=3)– 3 No genotypes performed (VL<1,000 c/mL)
• BLIPS (n=5)– 3 3TC/ABC– 2 FTC/TDF
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Adverse Events (AE) Summary
FTC/TDFn=155n (%)
3TC/ABC n=156 n (%)
Number of subjects with any treatment-emergent AE 112 (72) 120 (77)All Grades of Treatment-emergent AEsReported for ≥ 5% of Patients
Diarrhea 13 (8) 11 (7)
Headache 8 (5) 5 (3)Cough 8 (5) 8 (5)
Grade 3 or 4 Adverse Events 13 (8) 16 (10)Grade 3 or 4 AE related to Study Drug 1 (1) 0Serious AE 12 (8) 11 (7)AE Leading to Study Drug Discontinuation 7 (5) 3 (2) Renal events* 1 1 Death† 1 2 Other‡ 5 0
*Renal events: One subject discontinued FTC/TDF due to mild elevation in Cr from 1.0 to 1.3mg/dl; One subject discontinued 3TC/ABC due to renal failure/dehydration†Deaths: FTC/TDF arm 1 suicide; 3TC/ABC arm 1 homicide, 1 lymphoma‡Other: Multiple CNS symptoms and rash; malaise and lower back pain; decreased weight; cellulitis and streptococcal sepsis; and rash
Plotted median at each visit; p-values for comparison between treatment groups on change from baseline to Week 48 are from Wilcoxon Rank-Sum test
- 8.3- 4.2
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Fasting Lipids Change from Baseline Values at Week 48
-25
-20
-15
-10
-5
0
5
FTC/TDF3TC/ABC
Med
ium
Cha
nge
From
BL
at W
eek
48
(mg/
dL [m
mol
/L])
P =<0.001*
P =0.007*
P =0.26* P =0.074*
*p values for between arm differences from Wilcoxon rank-sum testTC = Total Cholesterol, LDL = Low-Density Lipoprotein, HDL = High-Density Lipoprotein, TG = Triglycerides
TC
LDL
HDL
TG-21[-0.54]
-3 [-0.08]
-7 [-0.18]
2 [0.05]
-1 [-0.03]-0 [0.00]
-18 [-0.20]
-9 [-0.10]
No significant difference between groups in total cholesterol/HDL ratio at Week 48
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Conclusions
• Through 48 weeks, switching to FTC/TDF was non-inferior to remaining on 3TC/ABC
• Significantly fewer subjects who switched to FTC/TDF experienced virologic failure compared to those who remained on 3TC/ABC through Week 48
• Switching to FTC/TDF resulted in significant improvement in fasting LDL and TC
• Declines in eGFR of unclear clinical significance were seen in both arms and were higher in the FTC/TDF arm
• Switching to FTC/TDF was safe and well tolerated with similar AEs observed between arms
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Acknowledgements
• All of the subjects
• All investigators who participated in the SWIFT study
• Thank you to the study team for their dedication David Piontkowsky, JD, MD Ramin Ebrahimi, MS
