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Background: Prospective studies examining long‐term therapeutic outcomes of the Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) regimen in human immunodeficiency virus (HIV) infection remain limited. This study assessed the actual efficacy and safety of BIC/FTC/TAF in HIV‐infected individuals in southwest China. Methods: This was a single‐center, prospective study enrolling ART‐naïve (n = 32) and ART‐experienced (n = 177) HIV‐infected patients administered BIC/FTC/TAF treatment between March 2022 and August 2022. The data were collected until February 28, 2023. Virological reactions and adverse events to the treatment were recorded, and patient subjective feelings in the form of Electronic Patient Reporting Outcome (ePRO) were collected. The primary endpoint was the rate of patients with HIV viral load <50 copies/mL at Week 24. Results: At Week 24, 87.5% and 95.5% of ART‐naïve and ART‐experienced HIV patients had a viral load <50 copies/mL, respectively. CD4 cell counts in ART‐naïve and ART‐experienced patients increased significantly by 163.5 cells/μL (p =.002) and 55.0 cells/μL (p =.022), respectively. By Week 24, no patients had discontinued the BIC/FTC/TAF treatment due to adverse events. Based on ePRO data, ART‐naïve and ART‐experienced patients at Week 24 had stable disease symptom burden, quality of life, and depression level after treatment with BIC/FTC/TAF. Conclusion: BIC/FTC/TAF reduces the viral load in ART‐naïve patients with high viral load as well as ART‐experienced patients with residual viremia. The patient's subjective experience was maintained stable after treatment with BIC/FTC/TAF. This study also revealed a very low incidence for BIC/FTC/TAF drug‐related side effects. [ABSTRACT FROM AUTHOR]