BACKGROUND: Since 2015, we prescribed dolutegravir (DTG)-based two drug regimens (DTG-2DR) for 620 people [total cohort 3133 (19.8%)]. METHOD: Clinic database search 1 January 15 to 31 October 21. Demographic, tolerability and HIV related data analysed. RESULTS: In total, 620 people identified; 561 had complete data. 446 male (79.5%); median age 54 years (interquartile range 46, 59). 343 (61.1%) MSM. Nine people who initiated naïvely achieved viral suppression (100%). 546/552 (99.0%) switched or continued and were suppressed at data censor. 460/552 (83.3%) received DTG-lamivudine (DTG/3TC), 74/552 (13.4%) received DTG-rilpivirine (DTG/RPV) and 18/552 (3.3%) received DTG-emtricitabine (DTG/FTC). 70 (12.5%) switched off DTG-2DR (55 DTG/3TC, 13 DTG/RPV, two DTG/FTC) due to side-effects. 41 episodes of blip (1 off >50 copies/ml) occurred in 30 people (5.3%). 11/41 on DTG-RPV [ n  = 7 multi-tablet regimen (MTR), n  = 4 single tablet regimen (STR)]. 27/41 DTG-3TC, 3/41 DTG/FTC ( n  = 26 MTR, n  = 4 STR). Six people (1.1%) failed (confirmed viral load >200 copies/ml or persistent low level viraemia) ( n  = 4 DTG-3TC STR, n  = 1 DTG-3TC MTR, n  = 1 DTG-RPV MTR). Four failures due to low level viraemia, one due to non-adherence and one due to high viral load. Resistance tests performed for 5/6 - mutations detected only in latter person with high viral load failure (on DTG-3TC MTR) who developed triple class resistance. CONCLUSION: Majority of experience is in DTG/3TC stable switch. Minority of patients developed side-effects. Low number of virological failures, one developed integrase inhibitor resistance. Viral failure associated with MTR, commensurate with trial data showing no failure with resistance if DTG/3TC STR used. Overall DTG-2DR demonstrates high efficacy in real-world setting.