Methods of Using SAHA for Treating HIV Infection

• US 20100324034A1
• Filed: 02/08/2008
• Published: 12/23/2010
• Est. Priority Date: 02/08/2007
• Status: Abandoned Application

• Current Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.), University of North Carolina At Chapel Hill (University of North Carolina System)
• Original Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Inventors: Archin, Nancie M., Margolis, David M., Espeseth, Amy S., Hazuda, Daria J.
• Application Number:
  US12/526,437
• Publication Number:
  US 20100324034A1
• Time in Patent Office: Days
• US Class Current: 514/230.5
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/536 ortho- or peri-condensed with carbocyclic ring systems
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/18 for HIV

Abstract

The present invention relates to pharmaceutical preparations and methods for treating individuals infected with the human immunodeficiency virus (HIV). The pharmaceutical preparations comprise SAHA and another anti-viral agent. The invention also relates to methods for treating HIV infected patients, particularly patients with persistent, latent HIV infection of CD4⁺ T cells, and thus make it possible to not just suppress but to eradicate the HIV infection.

Claims

1. A method of treating HIV infection in a subject, said method comprising the step of administering to the subject SAHA (suberoylanilide hydroxamic acid), represented by the structure:

2. The method of claim 1, wherein said anti-retroviral agent is selected from the group consisting of a nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, protease inhibitor, fusion inhibitor, entry inhibitor, integrase inhibitor, co-receptor antagonist, viral adsorption inhibitor, viral specific transcription inhibitor, and cyclin dependent kinase inhibitor and a combination thereof.

3. The method of claim 2, wherein said anti-retroviral agent is selected from the group consisting of a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor, an integrase inhibitor, and a combination thereof.

4. The method of claim 2, wherein said anti-retroviral agent is selected from the group consisting of efavirenz, indinavir sulfate and raltegravir potassium.

5. The method of claim 4, wherein said anti-retroviral agent is raltegravir potassium.

13. The method according to any one of claims 1, 5-8 and 12, wherein SAHA is the active ingredient.

6. A method of depleting latent HIV infection within resting CD4⁺ T cells comprising administering to the subject SAHA (suberoylanilide hydroxamic acid), represented by the structure:

7. A method of activating expression from the HIV long terminal repeat (LTR) promoter comprising the step of administering to the subject SAHA (suberoylanilide hydroxamic acid), represented by the structure:

8. A method of treating latent HIV infection in a subject, said method comprising the step of administering to the subject SAHA (suberoylanilide hydroxamic acid), represented by the structure:

9. The method of claim 8, wherein said anti-retroviral agent is selected from the group consisting of a nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, protease inhibitor, fusion inhibitor, entry inhibitor, integrase inhibitor, co-receptor antagonist, viral adsorption inhibitor, viral specific transcription inhibitor, and cyclin dependent kinase inhibitor and a combination thereof.

10. The method of claim 9, wherein said anti-retroviral agent is selected from the group consisting of a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor, an integrase inhibitor, and a combination thereof.

11. The method of claim 9, wherein said anti-retroviral agent is selected from the group consisting of efavirenz, indinavir sulfate and raltegravir potassium.

12. The method of claim 11, wherein said anti-retroviral agent is raltegravir potassium.

14. A pharmaceutical composition for treating HIV infection in a subject, comprising suberoylanilide hydroxamic acid (SAHA), represented by the structure:

15. The pharmaceutical composition of claim 14, wherein said anti-retroviral agent is selected from the group consisting of a nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, protease inhibitor, fusion inhibitor, entry inhibitor, integrase inhibitor, co-receptor antagonist, viral adsorption inhibitor, viral specific transcription inhibitor, and cyclin dependent kinase inhibitor and a combination thereof.

16. The pharmaceutical composition of claim 15, wherein said anti-retroviral agent is selected from the group consisting of a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor, an integrase inhibitor, and a combination thereof.

17. The pharmaceutical composition of claim 15, wherein said anti-retroviral agent is selected from the group consisting of efavirenz, indinavir sulfate and raltegravir potassium.

18. The pharmaceutical composition of claim 17, wherein said anti-retroviral agent is raltegravir potassium.