Background: The two-drug regimen of dolutegravir/lamivudine (DTG/3TC) is currently an optional antiretroviral therapy (ART). Despite its reported advantages on body weight and lipid profile, the same effects have not yet been reported for Asian population. Methods: We conducted a single-center retrospective study involving Japanese people living with HIV (PLWH). They were divided into four groups: those who had received abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) and continued the same (ABC-ON group) or switched to DTG/3TC (ABC-OFF group), those who had received tenofovir alafenamide fumarate/emtricitabine/dolutegravir (TAF/FTC/DTG) and continued the same (TAF-ON group) or switched to DTG/3TC (TAF-OFF group). We compared changes in viral load, CD4* cell count, CD4*/ CD8* ratio, body weight, BMI, lipid profiles, estimated glomerular filtration rate (eGFR), and fibrosis index based on four factors (FIB4-index) between the pre-switch and post-switch period. Results: Of the 541 PLWH on DTG-based ART, 165, 94, 264 and 18 constituted the ABC-ON, ABC-OFF, TAF-ON, and TAF-OFF groups, respectively. Neither viral rebound nor CD4+decline was observed in the post-switch period in all groups. Multivariate analysis showed significant reduction in total cholesterol, LDL-C and HDL-C in the ABC-OFF group (-6.280,-6.957 and-2.268, p = 0.040, 0.012 and 0.022, respectively), but not in the TAF-OFF group (-3.000, 6.708 and 0.046, p = 0.607, 0.276 and 0.983, respectively). No significant changes were observed in body weight, eGFR, or FIB4-index at 72 weeks after the discontinuation of ABC or TAF. Conclusions: Switching from ABC/3TC/DTG to DTG/3TC lowered lipids significantly, but not with TAF/FTC/ DTG. Neither switch affected body weight or other markers.