Objectives: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) is a recommended and widely used regimen for HIV infection. In this study, we aimed to determine the efficacy and safety of E/C/F/TAF in people living with HIV (PLWH), who are either treatment-naive or switched from any tenofovir disoproxil fumarate-containing regimen. For switched patients, we aimed to determine the impact of switching from tenofovir disoproxil fumarate (TDF) to TAF on lipid profile and kidney functions. Methods: ACTHIV-IST Study Group produced a database, and five dedicated HIV centres in Istanbul entered data of PLWH who switched from any TDF-containing regimen to E/C/F/TAF and treatment-naive patients who were initiated with the E/C/F/TAF regimen between January 2017 and December 2019. Clinical findings, viral parameters, lipid studies, renal function tests, adverse events and adherence to the treatment were recorded in this prospective observational study. Results: The study included a total of 614 switched and treatment-naive patients. Of 430 treatment-experienced patients, 89% (382) were men, and the mean age was 42 +/- 12 years. Among them, 47% (181/382) self-identified as men who have sex with men (MSM). The median duration of HIV diagnosis was 54 +/- 29 months. The median duration of E/C/F/TAF use was 20 +/- 36 months and that of previous treatment was 23 +/- 18 months. HIV-RNA was undetectable at baseline and month 12 in 84.1% (360/428) and 86.1% (328/381) of patients, respectively (p > 0.05). Mean CD4 counts were 708 +/- 287 cells/mu L and 802 +/- 305 cells/mu L at baseline and month 12, respectively (p < 0.001). Serum creatinine levels remained stable during the treatment period. Mean total cholesterol levels at baseline and month 12 were 172 and 211 mg/dL (p < 0.01), LDL-cholesterol 104 and 138 mg/dL (p < 0.01), HDL-cholesterol 39 and 49 mg/dL (p < 0.01) and triglycerides 134 and 174 mg/dL (p < 0.01), respectively. The treatment was generally well tolerated. Eight patients discontinued the therapy (drug interaction: 3; lost to follow-up: 1; pregnancy: 1; pulmonary tuberculosis: 1; side effect: 1; patient's decision: 1). Of 184 treatment-naive patients, 88% (162) were men, and the mean age was 36.5 +/- 12 years. Among them, 50% (81/162) self-identified as MSM. The mean duration of HIV infection was 21.6 +/- 17.1 months. The mean duration of E/C/F/TAF use was 16 +/- 4 months. HIV-RNA was undetectable at baseline and month 12 in 1% and 89.1% of patients, respectively. Mean CD4 counts at baseline and month 12 were 469 +/- 223 cells/mu L and 740 +/- 298 cells/mu L, respectively. During the treatment period, creatinine levels remained stable. Total cholesterol, LDL-cholesterol, triglyceride and also HDL-cholesterol levels increased. Mean total cholesterol levels at baseline and month 12 were 167 and 211 mg/dL (p < 0.01), LDL-cholesterol 108 and 143 mg/dL (p < 0.01), HDL-cholesterol 41 and 47 mg/dL (p < 0.01) and triglycerides 136 and 172 mg/dL, respectively (p < 0.01). The treatment was generally well tolerated. Three patients discontinued the therapy (drug interaction: 1; non-responder: 1; patient's decision: 1). Conclusion: Starting with or switching to E/C/F/TAF in PLWH effectively suppresses HIV infection, is associated with an increase in CD4 cell count and is well tolerated in a real-life setting. Renal functions remained stable during the treatment.