Effectiveness and Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide in People Living with HIV Aged 50 Years and Older: A Retrospective Analysis of Naïve and Treatment-Experienced Individuals

<b>Background</b>: The aging of people living with HIV (PLWH) necessitates antiretroviral regimens (ART) with high efficacy, a favorable safety profile, and minimal drug-drug interactions. We evaluated the real-world performance of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in PLWH aged ≥ 50 years, stratified by prior treatment experience. <b>Methods</b>: This retrospective cohort study included ART-naïve and virologically suppressed treatment-experienced PLWH aged ≥ 50 years who started B/F/TAF. Primary endpoints were virological suppression (HIV-1 RNA < 50 copies/mL) at 12 months ± 1 month and 24 months ± 1 month, and safety. Changes in immunological (CD4+ count, CD4+/CD8+ ratio), metabolic, and hepatic parameters were assessed. <b>Results</b>: Among 214 patients (37 naïve, 177 experienced; mean age 60.6 years), high virological suppression rates were observed in both naïve (85.7%) and experienced (93.9%) cohorts at 24 months. Immunologically, naïve patients experienced a robust increase in CD4+ counts (from 176 to 450 cells/μL, <i>p</i> < 0.001). A key finding was a significant increase in the CD4+/CD8+ ratio in the experienced cohort, which normalized from 0.95 at baseline to 1.12 at 24 months (<i>p</i> < 0.001). The regimen demonstrated a favorable safety profile: metabolic parameters remained stable, and hepatic enzymes significantly improved in naïve patients. Transient elastography confirmed no worsening of liver fibrosis or steatosis in experienced patients. The overall discontinuation rate was 19.2%, driven by different reasons between cohorts (e.g., comorbidities in naïve, strategic simplification in experienced). <b>Conclusions</b>: This real-world study confirms that B/F/TAF is a versatile cornerstone for the management of older PLWH. It demonstrates high efficacy in initiating treatment and is a safe, effective, and durable platform for treatment simplification. Its favorable metabolic and hepatic profile makes it particularly suitable for an aging population with a high burden of comorbidities, ensuring long-term treatment success.