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

Aim: With modern antiretroviral therapy (ART), HIV-1 has now become a manageable chronic condition. Among treatment-experienced (TE) people with HIV-1 (PWH), ART regimens can influence metabolic and renal outcomes and adverse events such as nausea. Regimen selection increasingly prioritizes safety, tolerability and long-term acceptability. This study compared bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) with other ART regimens in TE PWH using multilevel network meta-regression (ML-NMR), focusing on lipid profile, renal function and overall safety. Materials & methods: A systematic literature review (SLR) in June 2023 identified Phase III/IV randomized controlled trials reporting safety in adult TE PWH. ML-NMR was conducted at week 48 adjusting for age, sex, race and CD4 cell count, using individual patient data from three Phase III B/F/TAF trials (GS-US-380-1844,-1878,-4030) and aggregate data from comparator trials. Results: At week 48, B/F/TAF demonstrated similar changes in total cholesterol (TC) to HDL ratio and LDL versus comparators. Compared with NNRTI (+ or /) F/TDF, changes in TC favored B/F/TAF (mean difference [MD; 95% CrI]:-12.43 [-23.26,-1.53]), but favored the NNRTI-based regimen for HDL (-4.35 [-7.76,-0.70]). Triglycerides changes favored B/F/TAF versus DTG/ABC/3TC (-15.01 [-29.18,-1.06]) and protease inhibitor (+ or /) b + 2 NRTIs (-24.48 [-41.60,-7.47]). eGFR changes favored B/F/TAF versus DTG/ABC/3TC (3.81 [1.74, 5.97]). With some exceptions of statistical differences in both directions, B/F/TAF generally had similar levels of adverse events and discontinuations as other ART. Conclusion: Switching to or remaining on B/F/TAF in TE PWH was generally well tolerated and did not worsen lipid, renal or safety outcomes versus most other contemporary ART. Improvements in select lipid parameters and stable renal function, with low rates of adverse events and discontinuation, support B/F/TAF as a safe option for long-term management in TE PWH.