P061 Hepatic Safety of Bictegravir/Emtricitabine/Tenofovir ...
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Introduction ♦ Integrase strand transfer inhibitors (INSTIs) are recommended internationally in treatment guidelines for patients with HIV-1 infection, and the class is recognised for its potency and safety 1 ♦ Two INSTIs—dolutegravir (DTG) and raltegravir—have safety warnings for potential hepatotoxicity 2,3 ♦ Bictegravir (B) is an unboosted INSTI coformulated with emtricitabine (FTC; F) and tenofovir alafenamide (TAF) ♦ The single-tablet regimen B/F/TAF is a guideline-recommended regimen, with demonstrated long-term safety, efficacy, a high barrier to resistance, and few potential drug-drug interactions. ♦ B/F/TAF is approved for treatment-naïve patients and suppressed patients switching therapy, including those with HIV-1 and hepatitis B virus (HBV) coinfection Objective ♦ To assess the hepatic safety profile of B/F/TAF from two Phase 3 studies of treatment-naïve participants over 96 wk Methods ♦ Data for participants taking B/F/TAF were pooled from 2 randomised, double-blind, active-controlled studies Results ♦ Follow-up time included >1183 person-years of exposure to B/F/TAF ♦ No hepatic laboratory abnormalities led to discontinuation of study drug ♦ AST and ALT elevations were transient and resolved on study drug; all but 1 had identified aetiologies ♦ No participant met criteria for drug-induced liver injury ♦ 8 participants had HIV and HBV coinfection at baseline – 4 had HBV DNA <29 IU/mL at Week 96 – 3 had HBV DNA <29 IU/mL at their last study visit, but were missing HBV DNA results at Week 96 – 1 had no postbaseline data ♦ 2 HIV- and HBV-coinfected participants had Grade 3 or 4 ALT elevations – Both occurred at Week 12 with limited duration and resolved without interruption of study drug ♦ No participant with HIV and HBV coinfection had a hepatic AE ♦ No participant taking B/F/TAF had incident HBV infection while on study Hepatitis C Virus Coinfection Safety ♦ 5 participants had chronic HCV coinfection at baseline – 2 were treated for chronic HCV while on study and achieved a sustained virologic response (treatments: ledispavir/sofosbuvir and sofosbuvir/velpatasvir) ♦ 6 participants had incident HCV ♦ No hepatic AEs were reported in participants with HIV and HCV coinfection References: 1. British HIV Association. https://www.bhiva.org/HIV-1-treatment-guidelines; 2016; 2. Isentress [SMPC]. Haarlem, Netherlands: Merck Sharp & Dohme B.V, 2018; 3. Tivicay [SMPC]. Zeist, Netherlands: ViiV Healthcare BV, 2018. Acknowledgments: We extend our thanks to the participants, their partners and families, and all Study 1489 and 1490 investigators and staff. Study 1489: Albrecht H, Angel J, Antinori A, Arribas Lopez JR, Asmuth DM, Baumgarten A, Bennani Y, Benson P, Berhe M, Bordon J, Brar I, Brinson C, Brunetta J, Charest L, Cindrich R, Clarke A, Clotet B, Cook P, Cotte L, Coulston DR, Crofoot GE, Cruickshank FA, Cunningham D, Daar E, DeJesus E, De Wet JJ, Dietz C, Edelstein H, Estrada Perez V, Fichtenbaum C, Flamm J, Gallant J, Gathe JC, Girard P-M, Grossberg R, Gupta S, Hagins D, Hardy W, Hare CB, Henn S, Henry WK, Hileman C, Hite A, Hsiao CB, Jain M, Johnson M, Kasper K, Kinder CA, Klein D, Koenig E, Lazzarin A, LeBlanc R, LeBouche B, Lucasti C, Maggiolo F, Mallolas Masferrer J, Mayer C, McDonald C, McGowan JP, Meybeck A, Mills A, Miralles Alvarez C, Molina J-M, Moreno Guillen S, Mounzer K, Newman C, Orkin C, Osiyemi O, Palmieri PJ, Para M, Parks DA, Parsons C, Petroll A, Pierone G, Podzamczer D, Polk C, Portilla Sogorb J, Post F, Pozniak A, Prelutsky DJ, Pugliese P, Rachlis A, Ramgopal MN, Rashbaum BS, Richmond GJ, Roman A, Roberts A, Rockstroh J, Ross JD, Ruane PJ, Rubio Garcia R, Saag M, Santana-Bagur JL, Santiago Colon L, Schrader S, Scribner A, Shalit P, Shamblaw DJ, Shon A, Sims J, Slim J, Stellbrink H-J, Stephan C, Tebas P, Thompson MA, Towner WJ, Ustianowski A, Van Dam C, Vanderkerckhove L, Vandercam B, Vanig T, Voskuhl G, Wade BH, Walker D, Waters L, Wilkin A, Wohl DA, Wohlfeiler M, Workowski K, Wurapa A, Yazdanpanah Y, Young B, Zurawski C; Study 1490: Akil B, Albrecht H, Anday N, Angel J, Antinori A, Arastéh K, Arribas Lopez JR, Asmuth DM, Bartczak J, Bellos NC, Benson P, Berenguer J, Berger DS, Berhe M, Bloch M, Brar I, Brinson C, Brunetta J, Colson A, Cook PP, Coulston DR, Cox JJ, Creticos C, Crofoot GE Jr, Cruickshank FA, Cunningham DL, DeJesus E, Dietz C, Dronda F, Esser S, Fichtenbaum C, Flamm J, Florence E, Fox J, Gathe JC Jr, Gupta SK, Hagins DP, Hardy WD, Hassler SK, Hay P, Hsiao C-B, Hsu R, Jäger H, Jain M, Jayaweera DT, Johnson M, Johnson MA, Jordan WC, Kasper K, Kinder CA, Klein D, Koenig E, Lazzarin A, Lehmann C, Lutz T, Maggiolo F, Martorell CT, Mauss S, Mayer CA, McDonald C, McGowan J, McMahon J, Meybeck A, Mills A, Miralles Alvarez C, Mogyoros M, Moore R, Morales-Ramirez JO, Mounzer K, Nahass RG, Oguchi G, Orkin CM, Osiyemi O, Palacios R, Palmieri PJ, Parks D, Peyrani P, Podzamczer D, Portilla Sogorb J, Post FA, Pozniak AL, Prelutsky DJ, Pugliese P, Pulido F, Ramgopal M, Rashbaum B, Reynes J, Richmond GJ, Roberts A, Ross J, Roth N, Ruane PJ, Santiago Colon L, Sax PE, Scarsella AJ, Schembri G, Schmidt M, Scribner A, Shalit P, Sims J III, Sinclair G, Slim J, Sokol-Anderson ML, Stein DK, Stellbrink H-J, Stephan C, Stephens J, Taylor S, Tebas-Medrano P, Thompson MA, Towner WJ, Ustianowski AP, Van Dam C, Vandekerckhove L, Vanig TJ, Wade BH, Walmsley S, Warduglas J, Waters LJ, Wheeler DA, Wiberg K, Wilkin AM, Wohl D, Wohlfeiler MB, Woolley I, Workowski K, Wurapa AK, Yazdanpanah Y. Special thanks to the 1489 and 1490 study teams. These studies were funded by Gilead Sciences, Inc. ♦ There were no study drug-related hepatobiliary serious AEs or clinical AEs among 634 treatment-naïve participants taking B/F/TAF in two Phase 3 studies with >1183 patient-years of follow-up – 3 participants had transient liver-related laboratory abnormalities reported as AEs, which resolved while on B/F/TAF ♦ There were no treatment discontinuations due to either hepatobiliary AEs or abnormal liver function tests ♦ No participant had drug-induced liver injury ♦ Grade 3 or 4 liver function test abnormalities were transient and resolved while continuing B/F/TAF, and most had clear aetiologies ♦ B/F/TAF was safe in participants with HBV or HCV coinfection and effective at suppressing HBV viremia ♦ B/F/TAF provides a well-tolerated and effective treatment for HIV infection without evidence of hepatotoxicity Conclusions Presented at the 25th Annual Conference of the British HIV Association, 2‒5 April 2019, Bournemouth, UK © 2019 Gilead Sciences, Inc. All rights reserved. Hepatic Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide Margaret Johnson, 1 Stephen Taylor, 2 Xuelian Wei, 3 Sean E. Collins, 3 Hal Martin 3 1 Royal Free Hospital, London, UK; 2 University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 3 Gilead Sciences, Inc., Foster City, California, USA P061 Gilead Sciences, Inc. 333 Lakeside Drive Foster City, California, USA 94404 800-445-3235 B/F/TAF N=634 Median age, y (range) 32 (18‒71) Male, % 89 Race/ethnicity, % Black or African descent 33 Hispanic/Latino ethnicity 24 Median HIV-1 RNA, log 10 copies/mL (IQR) 4.42 (4.00‒4.88) HIV-1 RNA >100,000 copies/mL, % 19 Median CD4 cell count, cells/μL (IQR) 442 (293‒590) CD4 count <200 cells/μL, % 13 Asymptomatic HIV infection, % 90 Median eGFR CG , mL/min (IQR) 122 (104‒143) Baseline Characteristics IQR, interquartile range. B/F/TAF N=634 Participants, % (n) All AEs Hepatobiliary AEs* Any grade AE 91 4 (23) Grade 3 or 4 13 1 (5) † Study drug-related AE 24 <1 (4) Grade 3 or 4 1 <1 (1) ‡ Serious AE 14 <1 (2) § Study drug-related serious AE 1 0 AE leading to study drug discontinuation 1 0 Death ǁ 1 0 Overall Safety Through Week 96 *Includes adverse events (AEs) classified as hepatobiliary disorders and liver function-related investigations (MedDRA Version 21.0); † Acute hepatic failure from overdose, including acetaminophen/paracetamol (n=1), acute cholecystitis (also reported as serious AE; n=1), hepatocellular injury due to acute hepatitis A (also reported as serious AE; n=1), increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT; associated with elevated creatine kinase after physical activity; n=1), and increased AST, ALT, and γ-glutamyl transferase (GGT) at Week 72, which resolved on study drug (also reported as drug-related AE; n=1); ‡ Transient elevation of AST, ALT, and GGT at Week 72, which resolved on study drug (n=1); § Acute cholecystitis (n=1) and hepatocellular injury due to acute hepatitis A (n=1); ǁ Included recreational drug use (n=1), suicide (n=1), cardiac arrest (n=1), poorly differentiated gastric adenocarcinoma (n=1), and hypertensive heart disease with congestive heart failure (n=1). B/F/TAF All Grades Occurring in ≥3 Participants, n (%) N=634 All hepatobiliary disorders and liver-related laboratory AEs 23 (4) Increased AST 6 (1) Hepatic steatosis 5 (1) Increased ALT 5 (1) Increased GGT 3 (<1) Cholelithiasis 3 (<1) Grade 3 or 4 Hepatobiliary Disorders and Liver-Related Laboratory AEs: n=5 1. Acute hepatic failure due to overdose of acetaminophen/paracetamol, cocaine, and quetiapine 2. Acute cholecystitis 3. Hepatocellular injury due to acute hepatitis A 4. AST and ALT increased at Week 72, associated with increased creatine kinase after strenuous exercise, and returned to normal without study drug interruption 5. AST, ALT, and GGT increased at Week 72 and returned to below baseline on retest 11 d later without study drug interruption; pretreatment baseline labs included elevated GGT (Grade 3), ALT (Grade 2),and AST (Grade1) Hepatobiliary Adverse Events Through Week 96 B/F/TAF Grade 3 or 4, n (%) N=634 AST increased 18 (3) ALT increased 14 (2) GGT increased 6 (1) Bilirubin increased 4 (1) Alkaline phosphatase increased 1 (<1) Hepatic Laboratory Abnormalities Through Week 96 0 24 48 72 96 10 0 10 2 10 4 10 6 10 8 Study Week HBV DNA, Log IU/mL HBV DNA threshold 29 IU/mL Hepatitis B Coinfection Efficacy: n=8 0 24 48 72 96 0 24 48 72 96 10 0 10 2 10 4 10 6 10 8 10 0 10 2 10 4 10 6 10 8 0 500 1000 1500 2000 HBV DNA, Log IU/mL ALT, U/L ALT HBV DNA HBV DNA threshold 29 IU/mL HBV DNA threshold 29 IU/mL 0 500 1000 1500 2000 Study Week Participant 1 Participant 2 Study Week Hepatitis B Coinfection Safety Study 1489 (ClinicalTrials.gov NCT02607930) ■ HLA B*5701 negative ■ Chronic HBV negative ■ eGFR CG ≥50 mL/min B/F/TAF OD DTG/ABC/3TC OD DTG/ABC/3TC placebo OD B/F/TAF placebo OD 48 0 Week 1:1 n=314 n=315 B/F/TAF OD DTG + F/TAF OD DTG + F/TAF placebo OD B/F/TAF placebo OD 1:1 n=320 n=325 Primary Endpoint Key inclusion criteria for both: ■ No known resistance to FTC, TAF, ABC, or 3TC ■ HIV-1 RNA ≥500 copies/mL 96 Secondary Endpoints Study 1490 (NCT02607956) ■ Chronic HBV or HCV infection allowed ■ eGFR CG ≥30 mL/min Study Designs 3TC, lamivudine; ABC, abacavir; eGFR CG , estimated glomerular filtration rate by Cockcroft-Gault equation; HCV, hepatitis C virus; HLA, human leukocyte antigen.
Transcript of P061 Hepatic Safety of Bictegravir/Emtricitabine/Tenofovir ...
Introduction ♦ Integrase strand transfer inhibitors (INSTIs) are recommended internationally in
treatment guidelines for patients with HIV-1 infection, and the class is recognised for its potency and safety1
♦ Two INSTIs—dolutegravir (DTG) and raltegravir—have safety warnings for potential hepatotoxicity2,3
♦ Bictegravir (B) is an unboosted INSTI coformulated with emtricitabine (FTC; F) and tenofovir alafenamide (TAF)
♦ The single-tablet regimen B/F/TAF is a guideline-recommended regimen, with demonstrated long-term safety, efficacy, a high barrier to resistance, and few potential drug-drug interactions.
♦ B/F/TAF is approved for treatment-naïve patients and suppressed patients switching therapy, including those with HIV-1 and hepatitis B virus (HBV) coinfection
Objective ♦ To assess the hepatic safety profile of B/F/TAF from two Phase 3 studies of
treatment-naïve participants over 96 wk
Methods
♦ Data for participants taking B/F/TAF were pooled from 2 randomised, double-blind, active-controlled studies
Results
♦ Follow-up time included >1183 person-years of exposure to B/F/TAF
♦ No hepatic laboratory abnormalities led to discontinuation of study drug
♦ AST and ALT elevations were transient and resolved on study drug; all but 1 had identified aetiologies
♦ No participant met criteria for drug-induced liver injury
♦ 8 participants had HIV and HBV coinfection at baseline
– 4 had HBV DNA <29 IU/mL at Week 96
– 3 had HBV DNA <29 IU/mL at their last study visit, but were missing HBV DNA results at Week 96
– 1 had no postbaseline data
♦ 2 HIV- and HBV-coinfected participants had Grade 3 or 4 ALT elevations
– Both occurred at Week 12 with limited duration and resolved without interruption of study drug
♦ No participant with HIV and HBV coinfection had a hepatic AE
♦ No participant taking B/F/TAF had incident HBV infection while on study
Hepatitis C Virus Coinfection Safety ♦ 5 participants had chronic HCV coinfection at baseline
– 2 were treated for chronic HCV while on study and achieved a sustained virologic response (treatments: ledispavir/sofosbuvir and sofosbuvir/velpatasvir)
♦ 6 participants had incident HCV
♦ No hepatic AEs were reported in participants with HIV and HCV coinfection
References: 1. British HIV Association. https://www.bhiva.org/HIV-1-treatment-guidelines; 2016; 2. Isentress [SMPC]. Haarlem, Netherlands: Merck Sharp & Dohme B.V, 2018; 3. Tivicay [SMPC]. Zeist, Netherlands: ViiV Healthcare BV, 2018.
Acknowledgments: We extend our thanks to the participants, their partners and families, and all Study 1489 and 1490 investigators and staff. Study 1489: Albrecht H, Angel J, Antinori A, Arribas Lopez JR, Asmuth DM, Baumgarten A, Bennani Y, Benson P, Berhe M, Bordon J, Brar I, Brinson C, Brunetta J, Charest L, Cindrich R, Clarke A, Clotet B, Cook P, Cotte L, Coulston DR, Crofoot GE, Cruickshank FA, Cunningham D, Daar E, DeJesus E, De Wet JJ, Dietz C, Edelstein H, Estrada Perez V, Fichtenbaum C, Flamm J, Gallant J, Gathe JC, Girard P-M, Grossberg R, Gupta S, Hagins D, Hardy W, Hare CB, Henn S, Henry WK, Hileman C, Hite A, Hsiao
CB, Jain M, Johnson M, Kasper K, Kinder CA, Klein D, Koenig E, Lazzarin A, LeBlanc R, LeBouche B, Lucasti C, Maggiolo F, Mallolas Masferrer J, Mayer C, McDonald C, McGowan JP, Meybeck A, Mills A, Miralles Alvarez C, Molina J-M, Moreno Guillen S, Mounzer K, Newman C, Orkin C, Osiyemi O, Palmieri PJ, Para M, Parks DA, Parsons C, Petroll A, Pierone G, Podzamczer D, Polk C, Portilla Sogorb J, Post F, Pozniak A, Prelutsky DJ, Pugliese P, Rachlis A, Ramgopal MN, Rashbaum BS, Richmond GJ,
Roman A, Roberts A, Rockstroh J, Ross JD, Ruane PJ, Rubio Garcia R, Saag M, Santana-Bagur JL, Santiago Colon L, Schrader S, Scribner A, Shalit P, Shamblaw DJ, Shon A, Sims J, Slim J, Stellbrink H-J, Stephan C, Tebas P, Thompson MA, Towner WJ, Ustianowski A, Van Dam C, Vanderkerckhove L, Vandercam B, Vanig T, Voskuhl G, Wade BH, Walker D, Waters L, Wilkin A, Wohl DA, Wohlfeiler M, Workowski K, Wurapa A, Yazdanpanah Y, Young B, Zurawski C; Study 1490: Akil B, Albrecht H, Anday N,
Angel J, Antinori A, Arastéh K, Arribas Lopez JR, Asmuth DM, Bartczak J, Bellos NC, Benson P, Berenguer J, Berger DS, Berhe M, Bloch M, Brar I, Brinson C, Brunetta J, Colson A, Cook PP, Coulston DR, Cox JJ, Creticos C, Crofoot GE Jr, Cruickshank FA, Cunningham DL, DeJesus E, Dietz C, Dronda F, Esser S, Fichtenbaum C, Flamm J, Florence E, Fox J, Gathe JC Jr, Gupta SK, Hagins DP, Hardy WD, Hassler SK, Hay P, Hsiao C-B, Hsu R, Jäger H, Jain M, Jayaweera DT, Johnson M, Johnson MA, Jordan
WC, Kasper K, Kinder CA, Klein D, Koenig E, Lazzarin A, Lehmann C, Lutz T, Maggiolo F, Martorell CT, Mauss S, Mayer CA, McDonald C, McGowan J, McMahon J, Meybeck A, Mills A, Miralles Alvarez C, Mogyoros M, Moore R, Morales-Ramirez JO, Mounzer K, Nahass RG, Oguchi G, Orkin CM, Osiyemi O, Palacios R, Palmieri PJ, Parks D, Peyrani P, Podzamczer D, Portilla Sogorb J, Post FA, Pozniak AL, Prelutsky DJ, Pugliese P, Pulido F, Ramgopal M, Rashbaum B, Reynes J, Richmond GJ, Roberts A,
Ross J, Roth N, Ruane PJ, Santiago Colon L, Sax PE, Scarsella AJ, Schembri G, Schmidt M, Scribner A, Shalit P, Sims J III, Sinclair G, Slim J, Sokol-Anderson ML, Stein DK, Stellbrink H-J, Stephan C, Stephens J, Taylor S, Tebas-Medrano P, Thompson MA, Towner WJ, Ustianowski AP, Van Dam C, Vandekerckhove L, Vanig TJ, Wade BH, Walmsley S, Warduglas J, Waters LJ, Wheeler DA, Wiberg K, Wilkin AM, Wohl D, Wohlfeiler MB, Woolley I, Workowski K, Wurapa AK, Yazdanpanah Y.
Special thanks to the 1489 and 1490 study teams. These studies were funded by Gilead Sciences, Inc.
♦ There were no study drug-related hepatobiliary serious AEs or clinical AEs among 634 treatment-naïve participants taking B/F/TAF in two Phase 3 studies with >1183 patient-years of follow-up
– 3 participants had transient liver-related laboratory abnormalities reported as AEs, which resolved while on B/F/TAF
♦ There were no treatment discontinuations due to either hepatobiliary AEs or abnormal liver function tests
♦ No participant had drug-induced liver injury
♦ Grade 3 or 4 liver function test abnormalities were transient and resolved while continuing B/F/TAF, and most had clear aetiologies
♦ B/F/TAF was safe in participants with HBV or HCV coinfection and effective at suppressing HBV viremia
♦ B/F/TAF provides a well-tolerated and effective treatment for HIV infection without evidence of hepatotoxicity
Conclusions
Presented at the 25th Annual Conference of the British HIV Association, 2‒5 April 2019, Bournemouth, UK © 2019 Gilead Sciences, Inc. All rights reserved.
Hepatic Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide
Margaret Johnson,1 Stephen Taylor,2 Xuelian Wei,3 Sean E. Collins,3 Hal Martin3 1Royal Free Hospital, London, UK; 2University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 3Gilead Sciences, Inc., Foster City, California, USA
P061
Gilead Sciences, Inc. 333 Lakeside Drive
Foster City, California, USA 94404 800-445-3235
B/F/TAF N=634Median age, y (range) 32 (18‒71)Male, % 89Race/ethnicity, % Black or African descent 33 Hispanic/Latino ethnicity 24Median HIV-1 RNA, log10 copies/mL (IQR) 4.42 (4.00‒4.88) HIV-1 RNA >100,000 copies/mL, % 19Median CD4 cell count, cells/μL (IQR) 442 (293‒590) CD4 count <200 cells/μL, % 13Asymptomatic HIV infection, % 90Median eGFRCG, mL/min (IQR) 122 (104‒143)
Baseline Characteristics
IQR, interquartile range.
B/F/TAF N=634Participants, % (n) All AEs Hepatobiliary AEs*Any grade AE 91 4 (23) Grade 3 or 4 13 1 (5)†
Study drug-related AE 24 <1 (4) Grade 3 or 4 1 <1 (1)‡
Serious AE 14 <1 (2)§
Study drug-related serious AE 1 0AE leading to study drug discontinuation 1 0Deathǁ 1 0
Overall Safety Through Week 96
*Includes adverse events (AEs) classified as hepatobiliary disorders and liver function-related investigations (MedDRA Version 21.0); †Acute hepatic failure from overdose, including acetaminophen/paracetamol (n=1), acute cholecystitis (also reported as serious AE; n=1), hepatocellular injury due to acute hepatitis A (also reported as serious AE; n=1), increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT; associated with elevated creatine kinase after physical activity; n=1), and increased AST, ALT, and γ-glutamyl transferase (GGT) at Week 72, which resolved on study drug (also reported as drug-related AE; n=1); ‡Transient elevation of AST, ALT, and GGT at Week 72, which resolved on study drug (n=1); §Acute cholecystitis (n=1) and hepatocellular injury due to acute hepatitis A (n=1); ǁIncluded recreational drug use (n=1), suicide (n=1), cardiac arrest (n=1), poorly differentiated gastric adenocarcinoma (n=1), and hypertensive heart disease with congestive heart failure (n=1).
B/F/TAFAll Grades Occurring in ≥3 Participants, n (%) N=634All hepatobiliary disorders and liver-related laboratory AEs 23 (4) Increased AST 6 (1) Hepatic steatosis 5 (1) Increased ALT 5 (1) Increased GGT 3 (<1) Cholelithiasis 3 (<1)
Grade 3 or 4 Hepatobiliary Disorders and Liver-Related Laboratory AEs: n=51. Acute hepatic failure due to overdose of acetaminophen/paracetamol, cocaine, and quetiapine2. Acute cholecystitis 3. Hepatocellular injury due to acute hepatitis A4. AST and ALT increased at Week 72, associated with increased creatine kinase after strenuous exercise, and returned to normal without study drug interruption5. AST, ALT, and GGT increased at Week 72 and returned to below baseline on retest 11 d later without study drug interruption; pretreatment baseline labs included elevated GGT (Grade 3), ALT (Grade 2),and AST (Grade1)
Hepatobiliary Adverse Events Through Week 96
B/F/TAFGrade 3 or 4, n (%) N=634AST increased 18 (3)
ALT increased 14 (2)
GGT increased 6 (1)
Bilirubin increased 4 (1)
Alkaline phosphatase increased 1 (<1)
Hepatic Laboratory Abnormalities Through Week 96
0 24 48 72 96100
102
104
106
108
Study Week
HB
V D
NA
, Log
IU/m
L
HBV DNA threshold 29 IU/mL
Hepatitis B Coinfection Efficacy: n=8
0 24 48 72 96 0 24 48 72 96100
102
104
106
108
100
102
104
106
108
0
500
1000
1500
2000
HB
V D
NA
, Log
IU/m
L
ALT, U
/L
ALT HBV DNA
HBV DNA threshold 29 IU/mL HBV DNA threshold 29 IU/mL
0
500
1000
1500
2000
Study Week
Participant 1 Participant 2
Study Week
Hepatitis B Coinfection Safety
Study 1489 (ClinicalTrials.gov NCT02607930)■ HLA B*5701 negative■ Chronic HBV negative■ eGFRCG ≥50 mL/min
B/F/TAF OD
DTG/ABC/3TC OD
DTG/ABC/3TC placebo OD
B/F/TAF placebo OD
480Week
1:1
n=314
n=315
B/F/TAF OD
DTG + F/TAF OD
DTG + F/TAF placebo OD
B/F/TAF placebo OD
1:1
n=320
n=325
Primary Endpoint
Key inclusion criteria for both:■ No known resistance to FTC, TAF, ABC, or 3TC■ HIV-1 RNA ≥500 copies/mL
96
Secondary Endpoints
Study 1490 (NCT02607956)■ Chronic HBV or HCV infection allowed■ eGFRCG ≥30 mL/min
Study Designs
3TC, lamivudine; ABC, abacavir; eGFRCG, estimated glomerular filtration rate by Cockcroft-Gault equation; HCV, hepatitis C virus; HLA, human leukocyte antigen.
