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Injectable long-acting cabotegravir plus rilpivirine (CAB+RPV LA) is an effective treatment option for people living with HIV. Unlike regimens containing tenofovir with lamivudine (3TC) or emtricitabine (FTC), it lacks therapeutic activity against the hepatitis B virus, and hepatitis B vaccination is recommended for non-immune individuals. We present a case of acute hepatitis B after switching to CAB+RPV LA in a previously vaccinated individual.