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1. (WO2019046594) METHODS OF REACTIVATING LATENT HUMAN IMMUNODEFICIENCY VIRUS AND RELATED COMPOSITIONS
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CLAIMS:

1 . A method of reactivating a latent human immunodeficiency virus (HIV) in one or more cells of a patient infected with HIV, the method comprising administering a crotonylation-inducing agent to the patient to reactivate the latent HIV in the one or more cells of the patient.

2. The method of claim 1 , wherein the crotonylation-inducing agent is selected from at least one of sodium crotonate, crotonyl-coenzyme A (crotonyl-CoA), an agent that can activate crotonyl-CoA converting enzyme ACSS2, or an agent that can activate p300/CBP and/or MOF.

3. The method of claim 1 or 2, further comprising administering a histone deacetylase (HDAC) inhibitor to the patient.

4. The method of claim 3, wherein the HDAC inhibitor is selected from at least one of suberanilohydroxamic acid (SAHA), suberoyl bis-hydroxamic acid (SBHA), trichostatin A (TSA), scriptaid, oxamflatin, givinostat (ITF2357), belinostat (PXD101 ), droxinostat, romidepsin, panobinostat, CG05/CG06, valproic acid (VPA), sodium butyrate, or apicidin.

5. The method of any one of claims 1 -4, further comprising administering a protein kinase C (PKC) agonist to the patient.

6. The method of claim 5, wherein the PKC agonist is selected from at least one of ingenol-3-angelate (PEP005), 12-deoxyphorbol-13-acetate (prostratin), bryostatin-1 , or an analog thereof.

7. The method of any one of claims 1 -6, further comprising administering an anti-HIV antibody to the patient.

8. The method of any one of claims 1 -7, wherein the patient is being treated with a suppressive antiretroviral therapy (ART).

9. The method of any one of claims 1 -8, further comprising administering suppressive ART to the patient.

10. The method of any one of claims 1 -9, wherein the crotonylation-inducing agent is administered with at least one of a pharmaceutically acceptable carrier, an excipient, or a diluent.

1 1 . A method of treating human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) in a patient, the method comprising administering a crotonylation-inducing agent to the patient to reactivate a latent human immunodeficiency virus (HIV) in the patient.

12. The method of claim 1 1 , wherein the crotonylation-inducing agent is selected from at least one of sodium crotonate, crotonyl-coenzyme A (crotonyl-CoA), an agent that can activate crotonyl-CoA converting enzyme ACSS2, or an agent that can activate p300/CBP and/or MOF.

13. The method of claim 1 1 or 12, further comprising administering a histone deacetylase (HDAC) inhibitor to the patient.

4. The method of claim 3, wherein the HDAC inhibitor is selected from at least one of suberanilohydroxamic acid (SAHA), suberoyl bis-hydroxamic acid (SBHA), trichostatin A (TSA), scriptaid, oxamflatin, givinostat (ITF2357), belinostat (PXD101 ), droxinostat, romidepsin, panobinostat, CG05/CG06, valproic acid (VPA), sodium butyrate, or apicidin.

15. The method of any one of claims 1 1 -14, further comprising administering a protein kinase C (PKC) agonist to the patient.

16. The method of claim 15, wherein the PKC agonist is selected from at least one of ingenol-3-angelate (PEP005), 12-deoxyphorbol-13-acetate (prostratin), bryostatin-1 , or an analog thereof.

17. The method of any one of claims 1 1 -16, further comprising administering an anti-HIV antibody to the patient.

18. The method of any one of claims 1 1 -17, wherein the patient is being treated with a suppressive antiretroviral therapy (ART).

19. The method of any one of claims 1 1 -18, further comprising administering suppressive ART to the patient.

20. The method of any one of claims 1 1 -19, wherein the crotonylation-inducing agent is administered with at least one of a pharmaceutically acceptable carrier, an excipient, or a diluent.

21 . A pharmaceutical composition for treating a patient infected with a human immunodeficiency virus (HIV), the pharmaceutical composition comprising a crotonylation-inducing agent.

22. The pharmaceutical composition of claim 21 , wherein the crotonylation-inducing agent is selected from at least one of sodium crotonate, crotonyl-coenzyme A (crotonyl-CoA), an agent that can activate crotonyl-CoA converting enzyme ACSS2, or an agent that can activate p300/CBP and/or MOF.

23. The pharmaceutical composition of claim 21 or 22, further comprising a histone deacetylase (HDAC) inhibitor.

24. The pharmaceutical composition of claim 23, wherein the HDAC inhibitor is selected from at least one of suberanilohydroxamic acid (SAHA), suberoyl bis-hydroxamic acid (SBHA), trichostatin A (TSA), scriptaid, oxamflatin, givinostat (ITF2357), belinostat (PXD101 ), droxinostat, romidepsin, panobinostat, CG05/CG06, valproic acid (VPA), sodium butyrate, or apicidin.

25. The pharmaceutical composition of any one of claims 21 -24, further comprising a protein kinase C (PKC) agonist.

26. The pharmaceutical composition of claim 25, wherein the PKC agonist is selected from at least one of ingenol-3-angelate (PEP005), 12-deoxyphorbol-13-acetate (prostratin), bryostatin-1 , or an analog thereof.

27. The pharmaceutical composition of any one of claims 21 -26, further comprising an anti-HIV antibody.

28. The pharmaceutical composition of any one of claims 21 -27, further comprising at least one of a pharmaceutically acceptable carrier, an excipient, and a diluent.

29. A method of reactivating a latent virus in one or more cells of a patient infected with the virus, the method comprising administering a crotonylation-inducing agent to the patient to reactivate the latent virus in the one or more cells of the patient.

30. The method of claim 29, wherein the crotonylation-inducing agent is selected from at least one of sodium crotonate, crotonyl-coenzyme A (crotonyl-CoA), an agent that can activate crotonyl-CoA converting enzyme ACSS2, or an agent that can activate p300/CBP and/or MOF.

31 . The method of claim 29 or 30, further comprising administering a histone deacetylase (HDAC) inhibitor to the patient.

32. The method of claim 31 , wherein the HDAC inhibitor is selected from at least one of suberanilohydroxamic acid (SAHA), suberoyl bis-hydroxamic acid (SBHA), trichostatin A (TSA), scriptaid, oxamflatin, givinostat (ITF2357), belinostat (PXD101 ), droxinostat, romidepsin, panobinostat, CG05/CG06, valproic acid (VPA), sodium butyrate, or apicidin.

33. The method of any one of claims 29-32, further comprising

administering a protein kinase C (PKC) agonist to the patient.

34. The method of claim 33, wherein the PKC agonist is selected from at least one of ingenol-3-angelate (PEP005), 12-deoxyphorbol-13-acetate (prostratin), bryostatin-1 , or an analog thereof.

35. The method of any one of claims 29-34, further comprising administering an antibody that is specific to the virus to the patient.

36. The method of any one of claims 29-35, wherein the patient is being treated with a suppressive antiviral therapy.

37. The method of any one of claims 29-35, further comprising administering suppressive antiviral therapy to the patient.

38. The method of any one of claims 29-37, wherein the crotonylation-inducing agent is administered with at least one of a pharmaceutically acceptable carrier, an excipient, or a diluent.

39. A pharmaceutical composition for treating a patient infected with a virus, the pharmaceutical composition comprising a crotonylation-inducing agent.

40. The pharmaceutical composition of claim 39, wherein the crotonylation-inducing agent is selected from at least one of sodium crotonate, crotonyl-coenzyme A (crotonyl-CoA), an agent that can activate crotonyl-CoA converting enzyme ACSS2, or an agent that can activate p300/CBP and/or MOF.

41 . The pharmaceutical composition of claim 39 or 40, further comprising a histone deacetylase (HDAC) inhibitor.

42. The pharmaceutical composition of claim 41 , wherein the HDAC inhibitor is selected from at least one of suberanilohydroxamic acid (SAHA), suberoyl bis-hydroxamic acid (SBHA), trichostatin A (TSA), scriptaid, oxamflatin, givinostat (ITF2357), belinostat (PXD101 ), droxinostat, romidepsin, panobinostat, CG05/CG06, valproic acid (VPA), sodium butyrate, or apicidin.

43. The pharmaceutical composition of any one of claims 39-42, further comprising a protein kinase C (PKC) agonist.

44. The pharmaceutical composition of claim 43, wherein the PKC agonist is selected from at least one of ingenol-3-angelate (PEP005), 12-deoxyphorbol-13-acetate (prostratin), bryostatin-1 , or an analog thereof.

45. The pharmaceutical composition of any one of claims 39-44, further comprising an antibody specific to the virus.

46. The pharmaceutical composition of any one of claims 39-45, further comprising at least one of a pharmaceutically acceptable carrier, an excipient, and a diluent.