Long-term Analysis of B/F/TAF Treatment in HIV-Positive Adults

This study provides a comprehensive analysis of the long-term effectiveness and safety of B/F/TAF treatment in treatment-naive adults living with HIV over a four-year follow-up period. The research discusses participant disposition, baseline characteristics, study designs, and key inclusion criteria in detail. Findings shed light on the efficacy of B/F/TAF in maintaining viral suppression and managing the disease in this patient population through various endpoints.

• HIV
• Treatment
• Long-term
• Analysis
• Study

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1. Long-term Analysis of B/F/TAF in Treatment-Na ve Adults Living With HIV Through Four Years of Follow-up Jose Arribas,1Chloe Orkin,2Franco Maggiolo,3Andrea Antinori,4Adriano Lazzarin,5 Yazdan Yasdanpanah,6Hans-J rgen Stellbrink,7Anton Pozniak,8Edwin DeJesus,9 Hailin Huang,10Rima Acosta,10Diana Brainard,10Jason Hindman,10Hal Martin,10 Paul Sax11 on behalf of the Study 1489 and 1490 Investigators 1Hospital Universitario La Paz, Madrid, Spain; 2Ambrose King Centre, Royal London Hospital, London, UK; 3ASST Papa Giovanni XXIII, Bergamo, Italy; 4Istituto Nazionale Malattie Infettive, Lazzaro Spallanzani, Rome, Italy; 5Ospedale San Raffaele, Milano, Italy; 6H pital Bichat Claude-Bernard, Paris, France; 7ICH Study Center, Hamburg, Germany; 8Chelsea and Westminster Hospital, London; 9Orlando Immunology Center, Orlando, Florida, USA; 10Gilead Sciences, Inc., Foster City, California, USA; 11Brigham and Women s Hospital, Boston, Massachusetts, USA IAS 2021, 18 21 July: PEB151, 2137

2. Disclosures 2

3. Study Designs: Randomized, Double Blind, Active Controlled 2 Endpoint 1 Endpoint 2 Endpoint 2 Endpoint Week 0 48 96 144 192 240 Treatment-Na ve Adults B/F/TAF qd n=314 Study 1489 HLA B*5701 negative Negative for chronic HBV eGFRCG 50 mL/min DTG/ABC/3TC placebo qd 1:1 Open-label B/F/TAF DTG/ABC/3TC qd n=315 B/F/TAF placebo qd Key inclusion criteria for both: No known resistance to FTC, TAF, ABC, or 3TC HIV-1 RNA 500 copies/mL B/F/TAF qd n=320 DTG + F/TAF placebo qd Study 1490 Chronic HBV or HCV infection allowed eGFRCG 30 mL/min 1:1 Open-label B/F/TAF DTG + F/TAF qd n=325 B/F/TAFplacebo qd 3TC, lamivudine; ABC, abacavir; eGFRCG, estimated glomerular filtration rate by Cockcroft-Gault equation; HBV, hepatitis B virus; HCV, hepatitis C virus; HLA, human leukocyte antigen. 3

4. Participant Disposition Through Week 192 and Baseline Characteristics Participant Disposition Through Week 192 Baseline Characteristics Pooled B/F/TAF n=634 Randomized: N=1288 Randomized Phase Median age, y (range) 32 (18 71) DTG + F/TAF: n=330 B/F/TAF: n=643 DTG/ABC/3TC: n=315 Female at birth, n (%) 69 (11) Randomized, not treated: n=9 Randomized, not treated: n=5 Race/ethnicity, n (%) B/F/TAF: n=634 DTG/ABC/3TC: n=315 DTG + F/TAF: n=325 Black or African descent 211 (33) Premature D/C: n=115 (18%)* Hispanic/Latinx ethnicity 155 (24) Did not enter OLE: n=13 (2%) Median body weight, kg (Q1, Q3) 77 (68, 88) Median body mass index, kg/m2 (Q1, Q3) 25.1 (22.3, 28.6) Open Label B/F/TAF: n=506 Median HIV-1 RNA, log10copies/mL (Q1, Q3) 4.4 (4.0, 4.9) Reason for D/C, n* Participant decision Lost to follow-up AE Death Protocol violation Noncompliance 25 (5%) 12 9 1 1 1 1 HIV-1 RNA >100,000 copies/mL, n (%) 119 (19) Median CD4 cells/ L (Q1, Q3) 442 (293, 590) OLE CD4 count <200 cells/ L, n (%) 80 (13) Asymptomatic HIV infection, n (%) 572 (90) Median eGFRCG, mL/min (Q1, Q3) 122 (104, 143) On B/F/TAF to Data Cut Date: n=481 *In the randomized phase n=115 participants prematurely discontinued (D/C) study drug: 6 (1%) due to adverse event (AE), 0 due to lack of efficacy, and 109 (17%) due to other reasons; of the 506 who entered the OLE, 25 prematurely D/C study drug: 1 (<1%) due to AE, 0 due to lack of efficacy, and 24 (5%) due to other reasons. CD4, cluster of differentiation-4; Q, quartile. 4

5. Virologic Outcomes and Resistance HIV-1 RNA <50 Copies/mL CD4 Change From Baseline 100 99 99 99 99 99 99 98 Median Change From Baseline, 100 500 94 92 Cells/ L (Q1, Q3) 80 400 88 87 Participants, % 85 83 79 75 60 300 +289 40 200 20 100 Missing=excluded Missing=failure 0 0 0 48 96 144 192 0 24 48 72 96 120 144 168 192 Week Week M=E: n=* 634 607 589 564 557 543 531 505 480 n= 634 584 546 517 475 99% of B/F/TAF participants maintained HIV-1 RNA <50 copies/mL (M=E at Week 192) At Week 192, 476 participants had HIV-1 RNA <50 copies/mL and 4 participants had HIV-1 RNA >50 copies/mL All B/F/TAF Week 96 7 0 0 Participants, n Met criteria for resistance testing NRTI resistance detected INSTI resistance detected Week 48 8 0 0 Week 144 8 0 0 Week 192 8 0 0 No participant failed with resistance to any component of B/F/TAF *Participants with nonmissing HIV-1 RNA value; While receiving B/F/TAF (observed data); Resistance testing performed for participants with confirmed HIV-1 RNA 50 copies/mL with the confirmation visit having 200 copies/mL or 200 copies/mL at last visit, without resuppression of HIV-1 RNA to <50 copies/mL while on study drug. INSTI, integrase strand transfer inhibitor; M=E, missing=excluded; M=F, missing=failure; NRTI, nucleoside reverse-transcriptase inhibitor. 5

6. Treatment-Emergent AEs and AEs Leading to Discontinuation Through Week 192* B/F/TAF Overall: n=634 (Baseline Week 192) 94 B/F/TAF OLE: n=506 (Week 144 192) 70 B/F/TAF: n=634 Participants, % Any AE AEs 10% overall Diarrhea Headache Nasopharyngitis URTI Syphilis Arthralgia Back pain Nausea Cough Fatigue Insomnia Influenza Any study drug-related AE Study drug-related AEs 2% overall Headache Diarrhea Nausea Fatigue Dizziness Insomnia Cardiac arrest (Week 4; Day 28) AEs leading to D/C Not related n=3 (<1%) Paranoia (Week 42; Day 299) 21 18 18 16 15 13 13 13 13 11 10 10 28 4 4 6 5 5 3 4 3 5 2 2 3 2 Intervertebral discitis (Week 195; Day 1366) Chest pain (Week 0; Day 1) Abdominal distension (Week 0; Day 1) AEs leading to D/C Study drug related n=4 (1%) Sleep disorder, dyspepsia, and tension headache (Week 2; Day 15); depressed mood and insomnia (Week 9; Day 63) Depression (Week 48; Day 337) Cardiac arrest (Week 4; Day 28) Poorly differentiated gastric adenocarcinoma (Week 53; Day 376) Hypertensive heart disease (Week 58; Day 412) 5 5 4 3 2 2 <1 <1 <1 <1 <1 0 Deaths n=6 (1%) Self-inflicted wrist wound (Week 93; Day 656) Combined toxicity of chloroethane and methamphetamine (Week 110; Day 771) Sudden cardiac arrest (Week 151; Day 1060) *Red shading indicates AEs occurring during OLE. URTI, upper respiratory tract infection. Few AEs leading to B/F/TAF D/C were observed through 4 y of follow-up Only a small proportion of AEs leading to D/C occurred after Year 1 6

7. eGFRCG and Weight Changes eGFRCG Weight 5 8 Median Change From Baseline, +0.7 4 Median Change, kg/y Week 192 Week 144 Week 96 Week 48 +0.7 0 mL/min (Q1, Q3) +0.5 0.3 3 -8 -5.8 0.9 0.4 -7.5 -8.0 2 -8.8 +3.0 -16 1 -24 3 0 0 48 96 144 192 Week No reported cases of proximal renal tubulopathy or D/Cs due to renal AEs were observed on B/F/TAF Initial decline followed by stable eGFRCG are consistent with inhibition of tubular creatinine secretion via organic cation transporter-2 by BIC Most of the weight change took place in the first year, followed by annual changes of +0.5 0.7 kg/y 7

8. Conclusions In treatment-na ve people living with HIV, through 4 y of follow-up among those originally randomized to B/F/TAF, we observed: High rates of virologic suppression with no treatment-emergent resistance Few AEs leading to D/C, no renal related D/Cs overall, and AEs were rare between Weeks 144 192 9/634 participants (1%) experienced a treatment-emergent drug-related AE during the OLE Small changes in lipid fractions with minor change from baseline in TC:HDL ratio at Week 192 Weight gain of ~3 kg in the first year, followed by annual changes of +0.5 0.7 kg/y, consistent with data from previous studies in treatment-na ve populations, and similar to findings in the general population of increases in body mass index and weight of nearly 1 kg/y1-9 These results confirm the long-term safety and efficacy of B/F/TAF 1. Hill JO, et al. Science 2003;299:853-5; 2. Lakey W, et al. AIDS Res Hum Retroviruses 2013;29:435-40; 3. Sax PE, et al. Clin Infect Dis 2020;71:1379-89; 4. Sharma A, et al. PLoS One 2015;10:e0143740; 5. Taramasso L, et al. Open Forum Infect Dis 2017;4:ofx239; 6. Tate T, et al. Antivir Ther 2012;17:1281-9; 7. WHO 2016. Centers for Disease Control and Prevention. Obesity and overweight. 2016; 8. Workowski K, et al. CROI 2021, science spotlight 2268; 9. Yuh B, et al. Clin Infect Dis 2015;60:1852-9. 8