Comparative Safety of B/F/TAF vs. Other Antiretroviral Therapy Regimens for Treatment-Experienced People With HIV-1: A Systematic Literature Review and Indirect Comparisons Using Multilevel Network Meta-Regression
Author(s)
Tristan Curteis, MSc1, Lucy A. Eddowes, DPhil2, Andrei Karlsson, MMath3, Hannah Luedke, MRes3, Manon Rubinstein, MSc3, Mathias Hempfling, MSc1, Jonathan Gurney, MSc3, Elizabeth Sherman, PharmD4, Mehri S. McKellar, MD5, Ashley Lipps, MD, MPH6, Karam Mounzer, MD7, Ann M. Khalsa, MD8, Warren L. Dinges, MD, PhD9, Megan Chen, MSPH10, Uche Mordi, PharmD, MS10, Bhumi Gandhi-Patel, PharmD10, Nathan R. Unger, PharmD10.
1Costello Medical, Manchester, United Kingdom, 2Costello Medical, Bristol, United Kingdom, 3Costello Medical, London, United Kingdom, 4Nova Southeastern University, Fort Lauderdale, FL, USA, 5Division of Infectious Diseases, Duke University, Durham, NC, USA, 6Ohio State University Wexner Medical Center, Columbus, OH, USA, 7Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA, 8Valleywise Health McDowell Healthcare Center, Phoenix, AZ, USA, 9Seattle Infectious Disease Clinic, Seattle, WA, USA, 10Gilead Sciences, Inc., Foster City, CA, USA.
1Costello Medical, Manchester, United Kingdom, 2Costello Medical, Bristol, United Kingdom, 3Costello Medical, London, United Kingdom, 4Nova Southeastern University, Fort Lauderdale, FL, USA, 5Division of Infectious Diseases, Duke University, Durham, NC, USA, 6Ohio State University Wexner Medical Center, Columbus, OH, USA, 7Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA, 8Valleywise Health McDowell Healthcare Center, Phoenix, AZ, USA, 9Seattle Infectious Disease Clinic, Seattle, WA, USA, 10Gilead Sciences, Inc., Foster City, CA, USA.
OBJECTIVES: Antiretroviral therapy (ART) has significantly improved HIV management and life expectancy for people with HIV-1 (PWH). However, since current guideline recommended integrase strand transfer inhibitor (INSTI)-based regimens are effective at maintaining virologic control, there is growing interest in understanding differences in renal and other safety outcomes in treatment-experienced (TE) PWH. This study uses multilevel network meta-regression (ML-NMR) to compare renal safety and discontinuation outcomes for bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus other recommended ARTs in TE PWH.
METHODS: A systematic literature review (MEDLINE, Embase, CDSR, and CENTRAL databases; searched June 14, 2023) and supplementary searches (ClinicalTrials.gov; searched April 24, 2025) identified Phase 3/4 randomized controlled trials (RCTs) reporting safety outcomes in adult TE PWH. ML-NMR was deemed feasible and conducted at Week 48 for change from baseline in eGFR and all-cause discontinuation, with adjustment for age, sex, and race, using individual patient data from three Phase 3 B/F/TAF trials (GS-US-380-1844, GS-US-380-1878, GS-US-380-4030) and aggregate data from comparator trials.
RESULTS: Eight studies and eight different ART regimens were included in the analysis. Compared to B/F/TAF, ML-NMR results showed significantly greater decline in eGFR from baseline with dolutegravir/lamivudine (DTG/3TC) (mean difference [95% CrI]: -4.40 [-5.30, -3.51]) and DTG/abacavir/3TC (-3.60 [-5.74, -1.50]); change in eGFR was similar to DTG+F/TAF (-1.19 [-3.35, 1.06]). All-cause discontinuation was comparable across all treatments, with no significant risk differences (RD) for DTG/3TC (RD [95% CrI]: -0.01 [-0.05, 0.10]) or doravirine/islatravir (-0.01 [-0.04, 0.05]) versus B/F/TAF.
CONCLUSIONS: B/F/TAF demonstrated a more favorable renal safety profile compared to tenofovir-sparing DTG-based regimens, with similar all-cause discontinuation rates compared to other recommended ARTs, including DTG/3TC, and the investigational NRTI-sparing doravirine/islatravir. These findings support B/F/TAF as a renally safe and well-tolerated treatment option for TE PWH.
METHODS: A systematic literature review (MEDLINE, Embase, CDSR, and CENTRAL databases; searched June 14, 2023) and supplementary searches (ClinicalTrials.gov; searched April 24, 2025) identified Phase 3/4 randomized controlled trials (RCTs) reporting safety outcomes in adult TE PWH. ML-NMR was deemed feasible and conducted at Week 48 for change from baseline in eGFR and all-cause discontinuation, with adjustment for age, sex, and race, using individual patient data from three Phase 3 B/F/TAF trials (GS-US-380-1844, GS-US-380-1878, GS-US-380-4030) and aggregate data from comparator trials.
RESULTS: Eight studies and eight different ART regimens were included in the analysis. Compared to B/F/TAF, ML-NMR results showed significantly greater decline in eGFR from baseline with dolutegravir/lamivudine (DTG/3TC) (mean difference [95% CrI]: -4.40 [-5.30, -3.51]) and DTG/abacavir/3TC (-3.60 [-5.74, -1.50]); change in eGFR was similar to DTG+F/TAF (-1.19 [-3.35, 1.06]). All-cause discontinuation was comparable across all treatments, with no significant risk differences (RD) for DTG/3TC (RD [95% CrI]: -0.01 [-0.05, 0.10]) or doravirine/islatravir (-0.01 [-0.04, 0.05]) versus B/F/TAF.
CONCLUSIONS: B/F/TAF demonstrated a more favorable renal safety profile compared to tenofovir-sparing DTG-based regimens, with similar all-cause discontinuation rates compared to other recommended ARTs, including DTG/3TC, and the investigational NRTI-sparing doravirine/islatravir. These findings support B/F/TAF as a renally safe and well-tolerated treatment option for TE PWH.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
SA21
Topic
Study Approaches
Topic Subcategory
Meta-Analysis & Indirect Comparisons
Disease
Infectious Disease (non-vaccine)