•Switching from tenofovir disoproxil fumarate (TDF)-containing regimens has increased considerably in recent years.•A high proportion of people with a controlled viral load switched from TDF to tenofovir alafenamide (TAF).•Only 3.5% of patients switched from TDF to a dual therapy (DT) regimen.•Low eGFR was associated with a higher risk of switching to DT but not to TAF-based cART. Our aim was to evaluate the association between recent eGFR values and risk of switching from TDF to TAF or dual therapy (DT) in real life. HIV-positive patients achieving HIV-RNA ≤50 copies/mL for the first time after starting a TDF-based regimen were included. Kaplan–Meier (KM) curves and Cox regression models were used to estimate the time from TDF to switch to TAF or DT. 1486 participants were included: median (IQR) age 36 (30–42) years; baseline CKD-EPI eGFR 99.92 (86.47–111.4) mL/min/1.73m2. We observed a consistently higher proportion of people with HIV-RNA ≤50 copies/mL who switched from TDF to TAF rather than to DT. By competing risk analysis, at 2 years from baseline, the probability of switching was 3.5% (95% CI 2.6–4.7%) to DT and 46.7% (42.8–48.5%) to TAF. A significantly higher probability of switching to TAF was found for patients receiving INSTI at baseline versus NNRTIs and PI/b KM, 65.6% (61.7–69.4%) vs. 4.0% (1.8–6.1%) and 59.9% (52.7–67.2%), respectively; P < 0.0001. eGFR <60 mL/min/1.73m2 both as time-fixed covariate at baseline or as current value was associated with a higher risk of switching to DT aHR 6.68 (2.69–16.60) and 8.18 (3.54–18.90); P < 0.001 but not to TAF-based cART aHR 0.94 (0.39–2.31), P = 0.897; and 1.19 (0.60–2.38), P = 0.617. Counter to our original hypothesis, current eGFR is used by clinicians to guide switches to DT but does not appear to be a key determinant for switching to TAF.