OBJECTIVES: Our objective was to evaluate the efficacy, durability, and tolerability of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in a real-world setting in Belgium. METHODS: This was a retrospective, multicentre cohort study involving adult treatment-naïve (TN) and treatment-experienced (TE) people living with HIV receiving BIC/FTC/TAF between 1 January 2019 and 30 September 2020. The primary outcome was rate of virological suppression (plasma HIV-1 viral load <50 copies/mL; on-treatment analysis) at weeks 24 and 48. The main secondary outcomes included loss of virological suppression (LVS; two consecutive viral loads of >200 copies/mL after being virologically suppressed) by week 48 and analysis of resistance-associated mutations at time of LVS; tolerability of BIC/FTC/TAF over the 48-week study period; and change in weight and proportion of participants reporting a >10% weight gain at week 48. RESULTS: Overall, 2001 participants were included. Through 48 weeks, overall rate of virological suppression was 93.5%, with similar results observed in the following subgroups: age ≥50 years (92.7%), women (92.8%), Black sub-Saharan African (91%), TN (94%), TE (93.2%), and non-suppressed at baseline (86.6%). LVS was observed in 0.7% (n = 14) of participants, with one participant developing resistance-associated mutations to nucleoside reverse transcriptase inhibitors (184 V) and integrase strand transfer inhibitors (263KR). Of the 131 (6.5%) treatment discontinuations, the most common reason was an adverse event (2.4%), with the most frequent being central nervous system/psychiatric (0.4%) and gastrointestinal (0.4%) toxicity. Median weight gain at week 48 was 2 kg (interquartile range -1 to 5), and a >10% weight increase was observed in 11.6% of participants. CONCLUSION: In this large real-world cohort, BIC/FTC/TAF showed excellent virological efficacy in a diverse population of patients with HIV. Rare occurrence of emergent drug resistance was observed, and treatment was well ...