Use of bisphosphonates as hiv/aids adjunctive treatment

Abstract

The present invention relates to use of bisphosphonate formulations for the treatment and management of HIV/AIDS. The method of the invention comprises administering a formulation comprising an effective amount of a bisphosphonate that specifically inhibits the activity and/or decreases the number of monocytes and/or macrophages, thereby reducing or eliminating HIV reservoirs. The invention also provides a method of complementing an HIV antiviral therapy, such as the highly active antiretroviral therapy (HAART), with a bisphosphonate formulation to improve clinical outcome.

What is claimed is: 
     
         1 . A formulation containing an effective amount of a bisphosphonate having a particle size diameter in the range of about 0.03-1.0 microns, wherein the formulation is used to treat HIV infections. 
     
     
         2 . The formulation of  claim 1 , wherein said bisphosphonate is encapsulated in said particle. 
     
     
         3 . The formulation of  claim 2 , wherein said encapsulating particle is a liposome. 
     
     
         4 . The formulation of  claim 1 , wherein said bisphosphonate is embedded in said particle. 
     
     
         5 . The formulation of  claim 4 , wherein said embedding particle is selected from the group consisting of microparticles, nanoparticles, microspheres, and nanospheres. 
     
     
         6 . The formulation of  claim 1 , wherein said particle is bisphosphonate in particulate form. 
     
     
         7 . The formulation of  claim 6 , wherein said particulate form is selected from the group consisting of aggregates, flocculates, colloids, polymer chains, insoluble salts and insoluble complexes. 
     
     
         8 . The formulation of  claim 1 , wherein said bisphosphonate comprises a compound having formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1  is H, OH or halogen group; and 
         R 2  is halogen; linear or branched C 1 -C 10  alkyl or C 2 -C 10  alkenyl, optionally substituted by heteroaryl or heterocyclyl C 1 -C 10  alkylamino or C 3 -C 8  cycloalkylamino; —NHY where Y is hydrogen, C 3 -C 8  cycloalkyl, aryl or heteroaryl; or —SZ, where Z is chlorosubstituted phenyl or pyridinyl. 
       
     
     
         9 . The formulation of  claim 1 , wherein said bisphosphonate is selected from the group consisting of clodronate, etidronate, tiludronate, pamidronate, alendronate and risendronate. 
     
     
         10 . The formulation of  claim 1 , wherein said bisphosphonate is a nitrogenous bisphosphonate. 
     
     
         11 . The formulation of  claim 10 , wherein said bisphosphonate is alendronate. 
     
     
         12 . The formulation of  claim 1 , wherein said particle has a diameter of about 0.07-0.15 microns. 
     
     
         13 . The formulation of  claim 1 , wherein said particle is administered during an antiviral therapy. 
     
     
         14 . The formulation of  claim 13 , wherein said particle is administered within a short period before an interruption of an antiviral therapy, said short period selected from the group consisting of: 3 days, 5 days, 7 days and 10 days. 
     
     
         15 . The formulation of  claim 1 , wherein said particle is administered during an interruption of an antiviral therapy. 
     
     
         16 . The formulation of  claim 1 , where said particle is administered both during an antiviral therapy and during an interruption of an antiviral therapy. 
     
     
         17 . The formulation of  claim 13 , wherein the antiviral therapy is a highly active antiretroviral therapy (HAART). 
     
     
         18 . The formulation of  claim 1 , wherein administration of said particle formulation is selected from the group consisting of: intravenous, intra-arterial, intramuscular, subcutaneous or oral. 
     
     
         19 . The formulation of  claim 1 , wherein the formulation further comprises a non-bisphosphonate therapeutic agent.