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R Campo 1 , E DeJesus 2 , H Khanlou 3 , H Wang 4 , K White 4 ,

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;

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R Campo 1 , E DeJesus 2 , H Khanlou 3 , H Wang 4 , K White 4 ,

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  1. 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 Prevention July 17-20, 2011, Rome, Italy Oral Presentation WELBB03 Study GS-164-0216

  2. Background • 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 1. DHHS Guidelines, January 10, 2011, pp 51-52 2. Arribas, JR, ACTG 5202, JAIDS, 2008 3. Post FA, ASSERT, JAIDS, 2010 4. Mallal, S, HLA-B*5702, NEJM, 2008 5. D:A:D Study Group, Lancet, 2008 6. Saxs, 5202, NEJM, 2009 7. Martinez E, et al. BICOMBO, IAS 2007 8. Moyle G, et al. ROCKET I, HIV10 2010 2

  3. SWIFTStudy Design Prospective, open-label, multicenter, randomized, Phase 4, 48-week study conducted in Canada, Puerto Rico, and the United States FTC/TDF + PI/r n=155 3TC/ABC +PI/r for ≥3 months HIV RNA < 200c/mL ≥ 3 months N = 311 randomized and treated 48 weeks Randomized 1:1 3TC/ABC + PI/r n=156 No prior history of resistance to study drugs No CD4 restriction Stratified by PI: 32% LPV/r vs. 68% Non-LPV/r 3

  4. Study Endpoints • 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 *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

  5. Baseline Characteristics

  6. Subject Disposition through Week 48 *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) 6

  7. Primary Endpoint: TLOVR Responders with HIV-1 RNA <200 c/mL through Week 48 95% CI for difference (FTC/TDF- 3TC/ABC) ◄ Favors 3TC/ABC Favors FTC/TDF  % TLOVR Responders HIV-1 RNA < 200c/mL -5.1 3.0 11.2 -12 0 12 % Difference TLOVR Responder Rate

  8. *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 • 3TC/ABC VFs (n=11) • 8 No genotypes performed (VL<1,000 c/mL) • 3 Genotypes (no resistance to study drug) • #1: Wk 48 PI: L63T, A71V, V77I • #2: WK 48 PI: L33V, L63P, L89M • #3: WK 24 NNRTI: V90I, K103N, V179V/I • FTC/TDF VFs (n=3) • 3 No genotypes performed (VL<1,000 c/mL) • BLIPS (n=5) • 3 3TC/ABC • 2 FTC/TDF p=0.034 # Subjects with Virologic Failure

  9. Adverse Events (AE) Summary *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 9

  10. eGFR through 48 Weeks MDRD Cockcroft-Gault • 4.5 • 4.2 - 8.3 - 9.2 Estimated GFR by IBW CG (mL/min) p=0.012 Estimated GFR by MDRD (mL/min/1.73m2) p=0.008 FTC/TDF 3TC/ABC FTC/TDF 3TC/ABC Week Week 155 153 147 144 139 137156 153 150 146 142 139 FTC/TDF3TC/ABC 155 153 147 144 139 137156 153 150 146 142 139 FTC/TDF3TC/ABC 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 10

  11. Fasting Lipids Change from Baseline Values at Week 48 P =0.007* P =<0.001* P =0.26* P =0.074* 2 [0.05] -0 [0.00] -1 [-0.03] -3 [-0.08] HDL -7 [-0.18] Medium Change From BL at Week 48 (mg/dL [mmol/L]) -9 [-0.10] LDL -18 [-0.20] -21[-0.54] TG TC No significant difference between groups in total cholesterol/HDL ratio at Week 48 *p values for between arm differences from Wilcoxon rank-sum test TC = Total Cholesterol, LDL = Low-Density Lipoprotein, HDL = High-Density Lipoprotein, TG = Triglycerides

  12. 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

  13. 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 Todd Fralich, MD Maggie Wang, MS John Flaherty, PharmD Janet Ecker, BSN, MBA Lauren Dau, PharmD Naz Barlow, MS Kirsten White, PhD Betsy Leung, BS 13

  14. Back-up

  15. Forthcoming analysis to be presented at future conferences in 2011 • Analysis of secondary endpoints • Proportion of subjects with HIV‑1 RNA < 50 copies/mL • KM analysis proportion with VFs • Responses by stratified by: • Protease inhibitor used • Baseline comorbidities • CV/Framingham • Lipid analysis based NCEP thresholds and lipid lowering agents • Resistance in subject with detectable viremia 15

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