Methods for Treatment of HIV or Malaria Using Combinations of Chloroquine and Protease Inhibitors

Abstract

The present invention relates to a drug combination capable of conferring therapeutic benefits in the treatment of both AIDS and malaria. In particular, it relates to a drug combination including at least one quinolinic antimalarial compound such as chloroquine or hydroxychloroquine, and at least one inhibitor of the Human Immunodeficiency Virus (HIV) protease enzyme. This drug combination is capable of inhibiting the replication of both HIV and Plasmodium sp. It also relates to the direct antimalarial effects of the HIV PIs.

1 . A pharmaceutical composition for the treatment and/or prevention of malaria comprising a therapeutically effective amount of a combination of a quinolinic compound and an inhibitor of the human immunodeficiency virus (HIV) protease, wherein the combination is effective for the treatment and/or prevention of malaria. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the inhibitor of the HIV protease is selected from the group consisting of indinavir (IDV), ritonavir (RTV), saquinavir (SQV), nelfinavir (NFV), lopinavir (LPV), amprenavir (APV), fosamprenavir, tipranavir, atazanavir, TMC-114, and combinations thereof. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the quinolinic compound is selected from the group consisting of Chloroquine (CQ), Hydroxychloroquine (HCQ), Mefloquine (MQ), Quinine (Q), and combinations thereof. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the composition further comprises at least one nucleosidic inhibitor of the HIV Reverse Transcriptase (NRTI). 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the NRTI is selected from the group consisting of zidovudine (AZT or ZDV), lamivudine (3TC), abacavir (ABC), zalcitabine (ddC), didanosine (ddI), stavudine (d4T), tenofovir (TDF) emitricitabine (FTC), amdoxovir (DAPD), and combinations thereof. 
     
     
         6 . The pharmaceutical composition of  claim 3 , wherein the composition comprises from about 0.5% by weight to about 75% by weight of the quinolinic compound. 
     
     
         7 . The pharmaceutical composition of  claim 2 , wherein the composition comprises an amount of inhibitor of HIV protease sufficient to achieve a blood plasma concentration of from about 10 nM to about 30 •M. 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein the composition comprises from about 1 mg/kg of body weight to about 150 mg/kg of body weight of an inhibitor of HIV protease. 
     
     
         9 . The pharmaceutical composition of  claim 3 , wherein the composition comprises an amount of quinolinic compound sufficient to achieve a blood plasma concentration of from about 0.005 •M to about 6 •M. 
     
     
         10 . A pharmaceutical kit for treating and/or preventing malaria comprising a plurality of containers, wherein at least one of said containers contains a therapeutically effective amount of at least one quinolinic antimalarial compound selected from the group consisting of Chloroquine (CQ), Hydroxychloroquine (HCQ), Mefloquine (MQ), Quinine (Q), and combinations thereof, and at least one inhibitor of the HIV protease. 
     
     
         11 . The kit of  claim 10 , wherein the inhibitor of the HIV protease is selected from the group consisting of indinavir (IDV), ritonavir (RTV), saquinavir (SQV), nelfinavir (NFV), lopinavir (LPV), amprenavir (APV), fosamprenavir, tipranavir, atazanavir, TMC-114, and combinations thereof. 
     
     
         12 . The kit of  claim 11 , wherein the composition further comprises at least one nucleosidic inhibitor of the HIV Reverse Transcriptase (NRTI). 
     
     
         13 . The kit of  claim 12 , wherein the NRTI is selected from the group consisting of zidovudine (AZT or ZDV), lamivudine (3TC), abacavir (ABC), zalcitabine (ddC), didanosine (ddI), stavudine (d4T), tenofovir (TDF) emitricitabine (FTC), amdoxovir (DAPD), and combinations thereof.