Treatment of hepatitis delta virus infection

1. A method of reducing hepatitis delta virus (HDV) viral load in a human patient with a chronic HDV infection, comprising administering a lonafarnib-ritonavir co-therapy to the human patient, wherein lonafarnib is administered at least once per day.

2. The method of claim 1 , wherein ritonavir is administered at least once per day.

3. The method of claim 1 , wherein the co-therapy comprises administration of lonafarnib at a total daily dose of 100 mg.

4. The method of claim 1 , wherein the lonafarnib is administered at a dose of 25 mg BID to 100 mg BID and the ritonavir is administered at a dose of 50 mg BID to 100 mg BID or 100 mg QD.

5. The method of claim 1 , wherein lonafarnib is administered at a dose of 50 mg QD to 150 mg QD and ritonavir is administered at a dose of 100 mg QD.

6. The method of claim 1 , wherein at least one of lonafarnib or ritonavir is administered orally.

7. The method of claim 1 , wherein lonafarnib and ritonavir are administered together in a single unit dose form.

8. The method of claim 1 , wherein lonafarnib and ritonavir are administered as separate unit dose forms.

9. The method of claim 1 , wherein the human patient is treated with the lonafarnib-ritonavir co-therapy for at least 2 weeks, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, or at least 1 year.

10. The method of claim 1 , wherein lonafarnib and ritonavir are administered in amounts that result in serum lonafarnib concentrations greater than 2,000 ng/ml or greater than 4,000 ng/ml, or in a range from 3,500 ng/ml to about 7,500 ng/ml.

11. The method of claim 1 , wherein the human patient has a baseline viral load of at least 10 4 HDV RNA copies per mL serum before the initiation of treatment.

12. The method of claim 11 , wherein the lonafarnib-ritonavir co-therapy results in a reduction of viral load from at least 10 5 RNA copies per mL to less than 10 2 HDV RNA copies per mL serum.

13. The method of claim 11 , wherein the lonafarnib-ritonavir co-therapy results in a reduction of viral load from at least 10 7 RNA copies per mL to less than 10 5 HDV RNA copies per mL serum.

14. The method of claim 1 , wherein the lonafarnib-ritonavir co-therapy results in a reduction of HDV viral load of at least 1.5 log HDV RNA copies/mL serum.

15. The method of claim 1 , wherein the lonafarnib-ritonavir co-therapy results in a reduction of HDV viral load to an undetectable level.

16. The method of claim 1 , wherein the human patient experiences a sustained reduction in HDV RNA levels for a least one month.

17. The method of claim 1 , wherein after the human patient is determined to have a viral load of less than 10 2 HDV RNA copies per mL serum, treatment with lonafarnib-ritonavir co-therapy continues for at least 30 days.

18. The method of claim 1 , wherein the human patient experiences a decrease in HDV RNA levels of at least 1 log before experiencing an increase in HDV RNA levels of at least 50% or more from the nadir during treatment.

19. The method of claim 1 , wherein the human patient is also infected with hepatitis B virus (HBV) and experiences a transient increase of at least 3 log in HBV viral load.

20. The method of claim 1 , wherein the human patient has improved liver function during or after treatment.

21. The method of claim 1 , wherein during or after treatment the human patient has improved liver biopsy as assessed by one or more of the following: histological staining, immunohistochemical staining, and fibrosis grading.

22. The method of claim 1 , wherein the human patient has a delay in the need for a liver transplant for at least 3 months.

23. The method of claim 1 , wherein the human patient experiences an aminotransferase (ALT) flare.

24. The method of claim 1 , wherein the human patient has a baseline ALT level before initiation of treatment that is at least two-fold higher than upper limit of normal (ULN).

25. The method of claim 1 , wherein the human patient is treated for at least 24 weeks, and wherein the method results in a normalization of the human patient's alanine ATL level following an ATL flare.

26. The method of claim 23 , wherein the lonafarnib-ritonavir co-therapy is discontinued within 25 weeks following the ALT flare.

27. The method of claim 1 , wherein the lonafarnib-ritonavir co-therapy comprises administering lonafarnib QD or BID at a first dose for a first treatment period and administering lonafarnib QD or BID at a second dose for a second treatment period subsequent to the first treatment period.

28. The method of claim 27 , wherein the first dose is greater than the second dose.

29. The method of claim 27 , wherein the first dose is less than the second dose.

30. The method of claim 27 , wherein the first dose and the second dose are the same.

31. The method of claim 27 , wherein the first treatment period and the second treatment period are different lengths of time.

32. The method of claim 1 , wherein administration of the lonafarnib-ritonavir co-therapy to the human patient is ceased when HDV viral load is undetectable.

33. The method of claim 32 , wherein administration of the lonafarnib-ritonavir co-therapy to the human patient is resumed when HDV viral load is detectable again in the human patient.

34. The method of claim 1 , further comprising administering interferon alpha or interferon lambda to the human patient.

35. The method of claim 34 , wherein the interferon alpha or the interferon lambda is administered weekly at a dose of 120 micrograms per week or 180 micrograms per week.