Combinations of a pyrimidine containing nnrti with rt inhibitors

Abstract

The present invention concerns combinations of a pyrimidine containing NNRTI with nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors useful for the treatment of HIV infected patients or for the prevention of HIV transmission or infection.

1 . A combination comprising
 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]-amino]-benzonitrile, or a stereoisomeric form thereof, or a pharmaceutically acceptable salt thereof, and   tenofovir or tenofovir disoproxil fumarate, and   a nucleoside reverse transcriptase inhibitor that is emtricitabine, racemic FTC, or abacavir, or a pharmaceutically acceptable salt thereof;   wherein the 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]-amino]-benzonitrile, or a stereoisomeric form thereof; or a pharmaceutically acceptable salt thereof; the tenofovir or tenofovir disoproxil fumarate; and the nucleoside reverse transcriptase inhibitor are therapeutically effective HIV inhibitors at a dose that can be administered once daily.   
     
     
         2 . The combination of  claim 1 , wherein the 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]-amino]-benzonitrile, or a stereoisomeric form thereof; or a pharmaceutically acceptable salt thereof, is E-4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]-amino]-benzonitrile. 
     
     
         3 . The method of  claim 1 , wherein the 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]-amino]-benzonitrile, or a stereoisomeric form thereof; or a pharmaceutically acceptable salt thereof, is E-4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]-amino]-benzonitrile hydrochloride. 
     
     
         4 . The combination of  claim 2 , comprising tenofovir. 
     
     
         5 . The combination of  claim 3 , comprising tenofovir. 
     
     
         6 . The combination of  claim 1 , comprising between 10 mg and 500 mg of the 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]-amino]-benzonitrile or a stereoisomeric form thereof. 
     
     
         7 . The combination of  claim 1 , comprising between 10 mg and 300 mg of the 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]-amino]-benzonitrile or a stereoisomeric form thereof. 
     
     
         8 . The combination of  claim 1 , comprising about 25 mg of the 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]-amino]-benzonitrile or a stereoisomeric form thereof. 
     
     
         9 . The combination of  claim 1 , as a unitary pharmaceutically acceptable formulation. 
     
     
         10 . The combination of  claim 9 , wherein the unitary pharmaceutically acceptable formulation is selected from the group consisting of tablets, capsules, parenteral compositions, injectable solutions, and injectable suspensions. 
     
     
         11 . The combination of  claim 9 , wherein the unitary pharmaceutically acceptable formulation is a tablet. 
     
     
         12 . The combination of  claim 4 , as a unitary pharmaceutically acceptable formulation. 
     
     
         13 . The combination of  claim 12 , wherein the unitary pharmaceutically acceptable formulation is selected from the group consisting of tablets, capsules, parenteral compositions, injectable solutions, and injectable suspensions. 
     
     
         14 . The combination of  claim 12 , wherein the unitary pharmaceutically acceptable formulation is a tablet. 
     
     
         15 . The combination of  claim 5 , as a unitary pharmaceutically acceptable formulation. 
     
     
         16 . The combination of  claim 15 , wherein the unitary pharmaceutically acceptable formulation is selected from the group consisting of tablets, capsules, parenteral compositions, injectable solutions, and injectable suspensions. 
     
     
         17 . The combination of  claim 15 , wherein the unitary pharmaceutically acceptable formulation is a tablet. 
     
     
         18 . A method of treating HIV infection in a patient comprising administering to the patient the combination of  claim 1  once daily.