COMBINATIONS OF A PYRIMIDINE CONTAINING NNRTI WITH RT INHIBITORS
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
lamivudine;
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 lamivudine 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.