The prenyltransferase inhibitor lonafarnib and the CYP3A4 inhibitor ritonavir are used in combination to treat hepatitis delta virus (HDV) infection. HDV infection is treated by orally administering to the patient a therapeutically effective amount of lonafarnib and a therapeutically effective amount of a CYP3A4 inhibitor for at least 30 days. Optionally the treatment includes prophylactic administration of one or more GI modifying agents.
