Comparative safety of B/F/TAF versus other antiretroviral therapy regimens for treatment-naïve people with HIV-1: a systematic literature review and network meta-analysis.

Bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) is a single-tablet regimen approved for the treatment of HIV-1 in treatment-naive (TN) and virologically suppressed people with HIV-1 (PWH). While the efficacy of antiretroviral therapy (ART) regimens in TN PWH is well established, regimen selection is often influenced by safety and tolerability concerns. This systematic literature review and network meta-analysis compares the safety outcomes of B/F/TAF with other ART regimens in TN PWH, addressing a key aspect of therapeutic decision-making. A systematic literature review was performed to identify phase III and IV RCTs assessing B/F/TAF and comparator regimens in TN adults (≥18 years) with HIV-1. MEDLINE, Embase, Cochrane Database of Systematic Reviews and CENTRAL databases were last searched on 14 June 2023. Study design, population and outcome definitions were evaluated to ensure consistency across studies. Bayesian network meta-analyses were conducted where feasible, following key methodological guidelines. Nineteen studies were included in indirect comparisons following assessments of heterogeneity and network connectivity. B/F/TAF performed better than the majority of interventions in safety and tolerability outcomes, notably discontinuation due to adverse events (AEs), treatment-related AEs and nausea. Additionally, with comparable risk of experiencing grade 3/4 treatment-emergent AEs, diarrhea and all-cause discontinuation rates to other interventions, B/F/TAF was non-inferior to any other regimen for all outcomes. B/F/TAF typically outperformed interventions containing non-nucleoside reverse transcriptase inhibitor third agents in terms of treatment-related AEs, nausea, and discontinuation due to AEs, although treatment class effects were not estimated separately. This analysis highlights the favorable safety profile of B/F/TAF compared with other ART regimens in TN PWH, demonstrating that B/F/TAF remains a safe and well-tolerated ART option for most TN PWH.