Background <p>This study aimed to elucidate the efficacy and safety of treatment using a fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in older patients with HIV in the real world.</p> Methods <p>A retrospective study was conducted at our hospital between April 2023 and April 2024, and the efficacy and safety of treatment with fixed-dose BIC/FTC/TAF were assessed in 314 patients aged &gt; 50 years living with HIV, including 35 antiretroviral therapy (ART)-naïve patients and 279 ART-experienced patients.</p> Results <p>Fixed-dose BIC/FTC/TAF displayed good efficacy among older patients, even in five patients with the M184V mutation site. At the 48-week follow-up, the absolute change of bone mineral density (BMD) was compared with baseline values, with results as follows: 0.8876 ± 0.1193 vs. 0.9321 ± 0.1071 g/cm² in L1 (<i>p</i> = 0.030), 0.9260 ± 0.1327 vs. 0.9758 ± 0.1208 g/cm² in L2 (<i>p</i> = 0.029), 0.9559 ± 0.1386 vs. 1.0139 ± 0.1355 g/cm² in L3 (<i>p</i> = 0.018), and 0.9411 ± 0.1486 vs. 1.0250 ± 0.1709 g/cm² in L4 (<i>p</i> = 0.003). The BMD values in the left or right hip joint (neck, trochanter, and inside) and renal biomarkers tended to improve. Significantly increased serum creatinine and reduced eGFR levels were also observed (<i>p</i> &lt; 0.001). Changes in lipid panel values from baseline were as follows: 1.86 ± 1.21 mmol/L vs 1.66 ± 1.00 mmol/L for triglycerides (TGs) (<i>p</i> = 0.013) and 1.11 ± 0.30 mmol/L vs 1.15 ± 0.32 mmol/L for high-density lipoprotein (<i>p</i> = 0.018).</p> Conclusions <p>BIC/FTC/TAF presented optimal antiretroviral efficacy, including in patients with the M184V mutation site, and significantly improved outcomes in BMD in the lumbar spine and serum TG levels, while outcomes in the left or right hip joint, renal biomarkers, and other lipid panels presented improved trends after 48 weeks of treatment and follow-up in this real-world study.</p> Clinical trial number <p>Not applicable.</p>