This brief correspondence from a single center describes ART outcomes among five people who experienced virologic failure on bi-monthly cabotegravir/rilpivirine (CAB/RPV).  None of the patients had known pre-existing RPV or integrase inhibitor (INSTI) resistance associated mutations; four were on INSTI-based combinations prior to CAB/RPV and one was receiving RPV-based therapy (all were suppressed < 50 copies/mL at CAB/RPV initiation).  BMI ranged from 25 to 37 kg/m²; two individuals had subtype C infection, one subtype D, one subtype A, and one subtype AG.  All injections were administered within one week of the scheduled dose except for one case in which oral bridging ART was used for two months due to patient travel.  Viral load at CAB/RPV failure ranged from 1280 to 91,300 copies/mL, and both RT and integrase mutations were noted at time of confirmed virologic failure in all five.  Substitutions at position 148, with or without additional mutations at 138 in the integrase gene conferring intermediate bictegravir resistance, were noted among four individuals.  K101E and Y181C were each detected in two cases.  All five people were transitioned to bictegravir/emtricitabine/ tenofovir alafenamide and have maintained virologic suppression for a median of 11 months (range 6-18 months).