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Longer-term (96-week) Efficacy and Safety of Switching to Bictegravir, Emtricitabine, and Tenofovir Alafenamide (B/F/TAF

This study investigates the efficacy and safety of switching to B/F/TAF for 96 weeks in women living with HIV. Results show good tolerability, efficacy, and no resistance.

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Longer-term (96-week) Efficacy and Safety of Switching to Bictegravir, Emtricitabine, and Tenofovir Alafenamide (B/F/TAF

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  1. Longer-term (96-week) Efficacy and Safety of Switching to Bictegravir, Emtricitabine and Tenofovir Alafenamide (B/F/TAF) in Women Cissy Kityo,1 Debbie Hagins,2 Ellen Koenig,3Anchelee Avihingsanon,4Ploenchan Chetchotisakd,5Khuanchai Supparatpinyo,6 Natalya Gankina,7 Vadim Pokrovsky,8Evgenly Voronin,9 Jeffrey L. Stephens,10 Edwin DeJesus,11 Hui Wang,12 Rima Acosta,12Diana Brainard,12Hal Martin,12 Tariro Makadzange12 1Joint Clinical Research Centre, Kampala, Uganda; 2Georgia Department of Public Health, Coastal Health District, Chatham CARE Center, Savannah, GA; 3Zona Universitaria, Instituto Dominicano de EstudiosVirológicos, Santo Domingo, Dominion Republic; 4The HIV Netherlands Australia Thailand Research Collaboration, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand; 5Srinagarind Hospital, KhonKaen, Thailand; 6Chiang Mai University, Chiang Mai, Thailand; 7Krasnoyarsk Territorial Center for Prevention and Control of AIDS and Infectious Diseases, Krasnoyarsk, Russia; 8Center for Prevention and Control of AIDS, Moscow, Russia; 9Federal Budgetary Institution “Republican Clinical Infectious Hospital” of the Ministry of Health of the Russian Federation, Saint-Petersburg; 10Mercer University School of Medicine, Macon, GA; 11Orlando Immunology Center, Orlando, FL; 12Gilead Sciences Inc., Foster City, CA

  2. Disclosures and Acknowledgments Dr. Kityo has received research support and travel from Gilead Sciences. This study was funded by Gilead Sciences, Inc. We thank the participants and their families.

  3. Introduction • Bictegravir, coformulated into a single-tablet regimen with emtricitabine and tenofovir alafenamide (B/F/TAF), is a recommended regimen for initial treatment • Across all Phase 3 studies, B/F/TAF was safe and efficacious2-7 • Globally, women comprise at least 50% of people living with HIV1 • Week 48 results in a cis-women study of switching to B/F/TAF demonstrated good tolerability and efficacy, with no resistance8 1. UNAIDS. Fact Sheet–World AIDS Day 2017; 2. Gallant, Lancet 2017;390:2063-72; 3. Sax, Lancet 2017;390:2073-82. 4. Daar, Lancet HIV 2018;5:e347–56; 5. Molina, Lancet HIV 2018;5:e357–65; 6. Wohl, Lancet HIV 2019;6:e355–63; 7. Stellbrink, Lancet HIV 2019;6:e354-72; 8. Kityo, CROI 2018, #500.

  4. Study Design Primary Endpoint Secondary Endpoint N=470 women Extension phase Day 1 W48 W96 • Phase 3, randomized, open-label, multicenter, active-controlled study (NCT02652624) • Primary endpoint: proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48 • At Week 48, participants had option to receive B/F/TAF for an additional 48 weeks • We report efficacy and safety based on: • 96 weeks of exposure to B/F/TAF for Group A (secondary endpoint) • 48 weeks of exposure to B/F/TAF for Group B • Key inclusion criteria: • Suppressed on E/C/F/TAF or E/C/F/TDF or ATV + RTV + F/TDF • HIV-1 RNA <50 c/mL for ≥6 mo • eGFR ≥50 mL/min B/F/TAF* (Group A) n=234 1:1 Stay on baseline regimen (SBR)* Switch to B/F/TAF†(Group B) n=236 *Given with food; †Given without regard to food. ATV, atazanavir; C, cobicistat; E, elvitegravir; RTV, ritonavir.

  5. Enrollment by Country Uganda 127 Russia 112 Thailand 101 USA 72 Dominican Republic 58

  6. Disposition Randomized and treated, N=470 Randomized Phase Group A B/F/TAFn=234 SBR, n=236 Group B Switch to B/F/TAF n=228† Extension Phase Completedn=227 Completedn=222 *Reasons: pregnancy (n=3), SBR: Investigator discretion (n=2). lost to follow-up, pregnancy, and death (n=1 each); †Excludes n=3 included in randomized, but not extension phase due to pregnancy. AE, adverse event; D/C, discontinuation.

  7. Baseline Characteristics at Randomization  Data median (quartile [Q] 1, Q3) or n (%), except age, which is median (range). eGFRCG, estimated glomerular filtration rate by Cockcroft-Gault.

  8. Exposure to B/F/TAF

  9. Virologic Outcomes Weeks 48 and 96 (M=E Analysis) • Virologic suppression remained high through 96 weeks % Participants with HIV-1 RNA <50 copies/mL, M=E n N* = 229 230 191 194 420 424 207 208 • Group AB/F/TAF • Group BSBR to B/F/TAF • Groups A + B • All B/F/TAF • Group AB/F/TAF Week 48 Week 96 *Denominator based on M=E analysis.

  10. Resistance Analysis Population and Resistance Summary • Resistance-analysis population included participants with virologic failure and HIV-1 RNA ≥200 c/mL • Virologic rebound to HIV-1 RNA ≥50 c/mL after Day 1; confirmed ≥200 c/mL at subsequent visit, without resuppression • HIV-1 RNA ≥200 c/mL at Week 96 or last visit on study drug, without resuppression • 1 participant developed M184M/I/V in SBR group (E/C/F/TAF regimen) at Week 48 and subsequently resuppressed HIV-1 RNA after switching to B/F/TAF • No treatment emergent resistance on B/F/TAF in either group through Week 96 C, copies.

  11. Adverse Events • Majority of AEs reported were Grade 1 or 2 in severity *Regardless of relationship to study drug

  12. Adverse Events Attributed to Study Drug • Most AEs attributed to study drug were Grade 1 or 2 • No AE attributed to study drug was considered serious

  13. Grade 3-4 Laboratory Abnormalities • All cases of hematuria were related to menses LDL, low-density lipoprotein.

  14. Pregnancies while on B/F/TAF • Women who became pregnant on B/F/TAF discontinued study drug * 1 live birth of infant with patent urachus, requiring no intervention and was absent on repeat ultrasound. #1 twin pregnancy that resulted in fetal deaths: 1 in utero and 1 still-birth; both fetal deaths were reported as SAEs and were not attributed to study drug † Participants were lost to follow-up.

  15. Changes in eGFRCG Over Time • No discontinuations due to renal AEs and no proximal tubulopathy –1.4 –1.8 Median Change From BL eGFRCG, mL/min (Q1, Q3) –1.8 Week Group B, n= 228 216 224 193 Group A+B, n= 462 449 457 422 248 207

  16. Changes in Quantitative Proteinuria Groups A + B: All B/F/TAF (W48, N=462) Group A: B/F/TAF (W96, n=234) Group B: SBR to B/F/TAF (W48, n=228) UACR RBP:Cr β2M:Cr 57 41 38 28 26 47 13 19 12 Median % Change From BL (Q1, Q3) -35 -41 -43 -42 -33 -57 -57 -45 -56 β2M, β2 microglobulin; Cr, creatinine; RBP, retinol-binding protein; UACR, urine albumin:Cr ratio.

  17. Changes in Quantitative Proteinuria by Prior Treatment Regimen Non-TDF Containing at Baseline TDF-Containing at Baseline UACR RBP:Cr β2M:Cr UACR RBP:Cr β2M:Cr 65 59 54 49 38 38 39 23 19 4 -4 -13 Median % Change From BL (Q1, Q3) -28 -30 -32 -32 -39 -39 -42 -40 -51 -57 -76 -79 Group A: B/F/TAF (W96, n=110) Group A: B/F/TAF (W96, n=124) Group B: SBR to B/F/TAF (W48, n=109) Group B: SBR to B/F/TAF (W48, n=119)

  18. Changes in Fasting Lipid Parameters Groups A + B: All B/F/TAF (W48, N=462) Group A: B/F/TAF (W96, n=234) Group B: SBR to B/F/TAF (W48, n=228) Fasting Lipid Component • No clinically relevant changes from baseline were noted for fasting lipid parameters Total Cholesterol:HDL Total Cholesterol LDLCholesterol HDL Cholesterol Triglycerides Median at W48 or 96, mg/dL Median 189 194 192 131 135 128 56 56 56 97 103 100 3.3 3.4 3.4 Baseline 196 192 194 120 119 120 56 55 56 105 104 105 3.4 3.5 3.4 Change (Δ) ‒7 +2 ‒2 +11 +16 +8 0 +1 0 ‒8 ‒1 ‒ 5 ‒ 0.1 ‒0.1 0 HDL, high-density lipoprotein.

  19. Conclusions • In virologically suppressed women who switched to B/F/TAF: • Virologic suppression remained high through 96 weeks • No treatment-emergent resistancewas detected for B/F/TAF • Viremic participant with M184 mutation on her prior regimen rapidly suppressed after switching to B/F/TAF • B/F/TAF was well tolerated and improvements in renal tubule markers were observed • No clinically relevant changes from baseline were noted for fasting lipid parameters • B/F/TAF is a safe and highly efficacious treatment option for women living with HIV

  20. Study GS-US-380-1961 Study Investigators We thank Study GS-US-380-1961 Investigators and their study teams: Dominican Republic E Koenig, P Thormann Russian Federation E Belonosova, N Dushkina, N Gankina, I Klevtsova, O Kozyrev, M Kukushina, V Kulagin, A Kuznetsova, G Moshkovich, E Orlova-Morozova, V Orlovskiy, Y Plotnikova, V Pokrovsky, S Romanova, E Ryamova, T Shimonova, L Sultanov, E Voronin, A Yakovlev Thailand A Avihingsanon, P Chetchotisakd, S Kiertiburanakul, W Ratanasuwan, K Siripassorn, K Supparatpinyo UgandaC Kityo USAFA Cruickshank, E DeJesus, RH Dretler, F Garcia, JC Gathe, D Goldstein, R Grossberg, DP Hagins, DT Jayaweera, P Johnson III, M Johnson, CA Kinder, A LaMarca, CT Martorell, CA Mayer, C McDonald, JP McGowan, MS McKellar, G McLeod, JO Morales Ramirez, O Osiyemi, M Ramgopal, A Roberts, J Slim, ML Sokol-Anderson, J Stephens, MA Thompson, GW Voskuhl, BG Yangco

  21. Back up Slides

  22. M184V/I Isolate Suppressed Following Switch to B/F/TAF • E/C/F/TAF • B/F/TAF 1000 • One participant with prior suppression on EFV/FTC/TDF and subsequent E/C/F/TAF was randomized to the SBR arm (E/C/F/TAF), had virologic failure at Week 48 with 259 c/mL and emergent M184M/I/V in RT, and subsequently resuppressed when switched to B/F/TAF M184M/I/V substitution at failure 100 50 HIV-1 RNA, c/mL 10 No preexisting substitutions 1 0 24 48 72 96 120 Visit Date, Weeks

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