Multiple hepatitis co-infections are frequent in HIV-infected patients, often resulting in severe liver diseases that are difficult to treat. We report here the complete resolution of a chronic hepatitis B and D co-infection in a patient who was also infected with HCV and HIV. This cure was observed after 24weeks of combination therapy associating pegylated-IFN and ribavirin, which was initially given to treat HCV. An unexpected and extensive HDV replication was observed in this patient after HBs Ag had cleared from the serum, which was followed by a stable halt in HDV replication. Implications of this unusual observation will be discussed.