Treatment of hepatitis delta virus infection
Methods of reducing hepatitis delta virus (HDV) viral loads in a patient are provided. In some embodiments, the method comprises treating the patient with lonafarnib-ritonavir co-therapy. In some embodiments, the method further comprises treating the patient with an interferon.
1. A method for inducing immune reactivation in a patient infected with hepatitis delta virus (HDV) and hepatitis B virus (HBV), the method comprising:
(i) administering lonafarnib and ritonavir co-therapy to the patient, wherein the lonafarnib is administered at a dose of 25 mg BID or 50 mg BID and the ritonavir is administered at a dose of 100 mg BID to 200 mg BID; and
(ii) detecting a hepatitis flare in the patient.
2. The method of claim 1 , wherein the detecting step comprises measuring serum alanine aminotransferase (ALT) levels in the patient.
3. The method of claim 1 , wherein the lonafarnib and ritonavir co-therapy is administered for a period of 2 to 12 weeks.
4. The method of claim 1 , wherein the method further comprises administering an interferon to the patient.
5. The method of claim 4 , wherein the interferon is administered at a dose of 120 micrograms QW or 180 micrograms QW.
6. The method of claim 4 , wherein the interferon is interferon lambda.
7. A method for inducing immune reactivation in a patient infected with HDV and HBV, the method comprising administering to the patient lonafarnib at a first dose, followed by administering lonafarnib at a second dose, wherein the second dose is lower than the first dose.
8. The method of claim 7 , wherein the first dose is administered for at least 8 weeks and the second dose is administered for at least 4 weeks.
9. The method of claim 7 , wherein the first dose of lonafarnib is 50 mg BID and the second dose of lonafarnib is 25 mg BID.
10. A method for inducing immune reactivation in a patient infected with hepatitis delta virus (HDV) comprising:
administering lonafarnib-ritonavir co-therapy to the patient, wherein the lonafarnib is administered at a dose of 25 mg BID to 75 mg BID and the ritonavir is administered at a dose of 100 mg BID to 200 mg BID; and wherein the patient experiences a serum alanine aminotransferase (ALT) flare of over 5 fold the upper limit of normal (ULN) during treatment.
11. The method of claim 10 , wherein the 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.
12. The method of claim 10 , wherein the patient is also infected with hepatitis B virus (HBV) and experiences a transient increase of at least 3 log in HBV viral load.
13. The method of claim 10 , wherein the patient has improved liver function during or after treatment.
14. The method of claim 13 , wherein improvement in liver function is an improvement in one or more of serum albumin, bilirubin, ALT, aspartate aminotransferase (AST), or prothrombin activity by at least 10%, by at least 20%, or by at least 30%.
15. The method of claim 10 , wherein during or after treatment the patient has improved liver biopsy as assessed by one or more of the following: histological staining, immunohistochemical staining, and fibrosis grading.
16. The method of claim 10 , wherein the patient has a delay in the need for a liver transplant for at least 3 months.
17. The method of claim 10 , wherein the serum lonafarnib concentration is 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.
18. The method of claim 10 , wherein the patient has a baseline viral load of at least 10 4 HDV RNA copies per mL serum.
19. The method of claim 10 , wherein the patient has a baseline ALT level that is at least two fold higher than the ULN.
20. The method of claim 10 , wherein the patient experiences a sustained reduction in HDV RNA levels for a least one month.