Co-infection with HIV and hepatitis B virus (HBV) has serious long-term consequences. We describe a case of an HIV-infected heterosexual black African man with a delayed diagnosis of HBV infection. Baseline HBV screening was performed using a sequential testing algorithm starting with a total core antibody (anti-HBc) test, which was negative. He had no evidence of immunity against HBV and subsequently received three unsuccessful courses of HBV vaccination. He had mild but persistent elevation of liver enzymes over a five-year period despite maintaining full suppression of HIV replication on efavirenz, lamivudine and zidovudine; the latter was changed to abacavir due to lipoatrophy. Further testing revealed e-antibody positive chronic HBV infection with undetectable anti-HBc reactivity. High-grade HBV viraemia associated with L180M and M240V drug-resistance mutations was confirmed. He was subsequently switched to a tenofovir-based regimen, which achieved HBV suppression. Adopting effective HBV screening strategies in HIV-infected patients is recommended.