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/or 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
(i) 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]-amino]-benzonitrile, also named TMC278, or a stereoisomeric form thereof; or a pharmaceutically acceptable salt thereof; or a prodrug thereof; and
(ii) a nucleoside reverse transcriptase inhibitor and/or a nucleotide reverse transcriptase inhibitor; wherein TMC278 and the nucleotide reverse transcriptase inhibitor and the nucleoside reverse transcriptase inhibitor are therapeutically effective HIV inhibitors at a dose that can be administered once daily.
2 . The combination according to claim 1 comprising
(i) TMC278, or a stereoisomeric form thereof; or a pharmaceutically acceptable salt thereof; or a prodrug thereof; and
(ii) a nucleoside reverse transcriptase inhibitor; wherein TMC278 and the nucleoside reverse transcriptase inhibitor are therapeutically effective HIV inhibitors at a dose that can be administered once daily.
3 . The combination according to claim 1 comprising
(i) TMC278, or a stereoisomeric form thereof; or a pharmaceutically acceptable salt thereof; or a prodrug thereof; and
(ii) a nucleotide reverse transcriptase inhibitor; wherein TMC278 and the nucleotide reverse transcriptase inhibitor are therapeutically effective HIV inhibitors at a dose that can be administered once daily.
4 . The combination according to claim 1 comprising
(i) TMC278, or a stereoisomeric form thereof; or a pharmaceutically acceptable salt thereof; or a prodrug thereof; and
(ii) a nucleoside reverse transcriptase inhibitor; and
(iii) a nucleotide reverse transcriptase inhibitor; wherein TMC278 and the nucleotide reverse transcriptase inhibitor and the nucleoside reverse transcriptase inhibitor are therapeutically effective HIV inhibitors at a dose that can be administered once daily.
5 . The combination according to claim 1 comprising
(i) TMC278, or a stereoisomeric form thereof; or a pharmaceutically acceptable salt thereof; or a prodrug thereof; and
(ii) a nucleoside reverse transcriptase inhibitor; and
(iii) a second nucleoside reverse transcriptase inhibitor other than the nucleoside reverse transcriptase inhibitor of (ii); wherein TMC278 and the nucleoside reverse transcriptase inhibitors are therapeutically effective HIV inhibitors at a dose that can be administered once daily.
6 . The combination according to claim 1 , wherein TMC278 occurs in its E-isomeric form.
7 . The combination according to claim 1 , wherein the nucleotide reverse transcriptase inhibitor and/or the nucleoside reverse transcriptase inhibitor or inhibitors select mutations in the reverse transcriptase that do not cause resistance to TMC278.
8 . The combination according to claim 1 wherein the nucleotide reverse transcriptase inhibitor is tenofovir or its prodrug tenofovir disoproxil fumarate.
9 . The combination according to claim 1 wherein the nucleoside reverse transcriptase inhibitor is emtricitabine, racemic FTC, lamivudine (also named 3TC), abacavir or a pharmaceutically acceptable salt thereof.
10 . The combination according to claim 1 wherein the nucleoside reverse transcriptase inhibitor is emtricitabine.
11 . The combination according to claim 1 wherein the combination comprises
(i) TMC278 or a pharmaceutically acceptable salt, and
(ii) tenofovir or its prodrug tenofovir disoproxil fumarate, and
(iii) emtricitabine.
12 . The combination according to claim 1 wherein the nucleoside reverse transcriptase inhibitor is lamivudine.
13 . The combination according to claim 8 wherein the combination comprises
(i) TMC278 or a pharmaceutically acceptable salt, and
(ii) tenofovir or its prodrug tenofovir disoproxil fumarate, and
(iii) lamivudine.
14 . The combination according to claim 1 wherein the nucleoside reverse transcriptase inhibitor is abacavir or a pharmaceutically acceptable salt thereof.
15 . The combination according to claim 14 wherein the combination comprises
(i) TMC278 or a pharmaceutically acceptable salt, and
(ii) tenofovir or its prodrug tenofovir disoproxil fumarate, and
(iii) abacavir or a pharmaceutically acceptable salt thereof.
16 . The combination according to claim 1 wherein the combination comprises
(i) TMC278 or a pharmaceutically acceptable salt, and
(ii) lamivudine, and
(iii) emtricitabine.
17 . The combination according to claim 1 wherein the combination comprises
(i) TMC278 or a pharmaceutically acceptable salt, and
(ii) abacavir, or a pharmaceutically acceptable salt thereof; and
(iii) emtricitabine.
18 . The combination according to claim 1 wherein the combination comprises
(i) TMC278 or a pharmaceutically acceptable salt, and
(ii) lamivudine, and
(iii) abacavir, or a pharmaceutically acceptable salt thereof.
19 . The combination according to claim 1 wherein weight ratio of each couple of components of the triple combination taken on a daily basis may vary in a range from 1/4 to 4/1.
20 . A product containing a combination as claimed in claim 1 as a combined preparation for simultaneous, separate or sequential use against HIV infection.
21 . A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and a combination as claimed in claim 1 .
22 . The formulation of claim 21 comprising as active ingredients (i) TMC278 or its stereoisomeric form or pharmaceutically acceptable salt or its prodrug, and (ii) a nucleoside reverse transcriptase inhibitor, and (iii) a nucleotide reverse transcriptase inhibitor.
23 . A combination as claimed in claim 1 for use as a medicine.
24 . Use of a combination as claimed in claim 1 for the manufacture of a medicament for the prevention of HIV infection or transmission via sexual intercourse or related intimate contact between partners.