Composition and methods used during anti-hiv treatment

Abstract

This invention relates to a composition comprising an anti-HIV treatment and a treatment for side effects of said anti-HIV treatment in an HIV-infected patient. This invention is, for example, very useful in the treatment of side effects caused by certain anti-HIV treatments, for example premature aging and lipodystrophy, which can be caused by protease inhibitors or reverse transcriptase inhibitors. The composition of this invention includes at least one hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, at least one farnesyl-pyrophosphate synthase inhibitor, and at least one anti-HIV agent. One of the processes for treating an HIV-infected patient includes, in any order, the following steps: (i) administration of a mixture including at least one hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor and at least one farnesyl-pyrophosphate synthase inhibitor and (ii) administration of an anti-HIV agent, in which the administrations are concomitant, successive or alternative.

1 . Composition comprising:
 at least one hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor or one of its physiologically acceptable salts,   at least one farnesyl-pyrophosphate synthase inhibitor or one of its physiologically acceptable salts, and   at least one anti-HIV agent.   
     
     
         2 . Composition according to  claim 1  in which the HMB-CoA reductase inhibitor is a molecule of the family of statins or one of its physiologically acceptable salts. 
     
     
         3 . Composition according to  claim 2  in which the HMG-CoA reductase inhibitor is a hydrosoluble statin. 
     
     
         4 . Composition according to  claim 2  in which the HMG-CoA reductase inhibitor is chosen from the group comprising atorvastatin, simvastatin, pravastatin, rivastatin, mevastatin (or compactin), fluindostatin, velostatin, fluvastatin, dalvastatin, cerivastatin, pentostatin, rosuvastatin, lovastatin, pitavastatin, or their physiologically acceptable salts. 
     
     
         5 . Composition according to  claim 1  in which the farnesyl-pyrophosphate synthase inhibitor is chosen from the group comprising a molecule of the aminobiphosphonate (NEP) family or one of its physiologically acceptable salts. 
     
     
         6 . Composition according to  claim 5  in which the aminobiphosphonate can be chosen from:
 alendronic acid or its ionic form, alendronate; 
 clodronic acid or its ionic form, clodronate; 
 etidronic acid or its ionic form, etidronate; 
 ibandronic acid or its ionic form, ibandronate; 
 medronic acid or its ionic form, medronate; 
 neridronic acid or its ionic form, neridronate; 
 olpadronic acid or its ionic form, olpadronate; 
 pamidronic acid or its ionic form, pamidronate; 
 risedronic acid or its ionic form, risedronate; 
 tiludronic acid or its ionic form, tiludronate; 
 zoledronic (or zolendronic) acid or its ionic form, zoledronate (or zolendronate); 
 4-N,N-dimethylaminomethane diphosphonic acid or its ionic form, dimethylaminomethanediphosphonate; 
 α-amino-(4-hydroxybenzylidene)diphosphonate. 
 
     
     
         7 . Composition according to  claim 1  in which the farnesyl-pyrophosphate synthase inhibitor is zoledronic acid or its ionic form, zoledronate. 
     
     
         8 . Composition according to  claim 1  in which the anti-HIV agent is an antiretroviral agent or a mixture of antiretroviral agents. 
     
     
         9 . Composition according to  claim 1  in which the anti-HIV agent is a protease inhibitor or a reverse transcriptase inhibitor. 
     
     
         10 . Composition according to  claim 1  in which the anti-HIV agent is a protease inhibitor chosen from the group comprising fosamprenavir, lopinavir, ritonavir, amprenavir, atazanavir and indinavir. 
     
     
         11 . Composition according to  claim 1  in which the anti-HIV agent is a reverse transcriptase inhibitor chosen from the group comprising zidovudine, lamivudine, didanosine and epzicom. 
     
     
         12 . Process for treating an HIV-infected patient comprising the administration of a composition according to  claim 1 . 
     
     
         13 . Process according to  claim 12 , in which the administration is performed orally or by injection. 
     
     
         14 . Process for treating side effects of premature aging and/or lipodystrophy caused in a patient by an anti-HIV treatment, which process comprises the administration of a mixture comprising at least one hydroxymethylgiutaryl coenzyme A (HMG-CoA) reductase inhibitor and at least one farnesyl-pyrophosphate synthase inhibitor. 
     
     
         15 . Process according to  claim 14 , in which the HMG-CoA reductase inhibitor is a molecule of the statin family or 25 one of its physiologically acceptable salts. 
     
     
         16 . Process according to  claim 14 , in which the HMG-CoA reductase inhibitor is a hydrosoluble statin. 
     
     
         17 . Process according to  claim 14 , in which the HMG-CoA reductase inhibitor is chosen from the group comprising atorvastatin, simvastatin, pravastatin, rivastatin, mevastatin (or compactin), fluindostatin, velostatin, fluvastatin, dalvastatin, cerivastatin, pentostatin, rosuvastatin, lovastatin, pitavastatin, and their physiologically acceptable salts. 
     
     
         18 . Process according to  claim 14 , in which the farnesyl-pyrophosphate synthase inhibitor is chosen from the group comprising a molecule of the aminobiphosphonate (NBP) family or one of its physiologically acceptable salts. 
     
     
         19 . Process according to  claim 18 , in which the aminobiphosphonate can be chosen from:
 alendronic acid or its ionic form, alendronate;   clodronic acid or its ionic form, clodronate;   etidronic acid or its ionic form, etidronate;   ibandronic acid or its ionic form, ibandronate;   medronic acid or its ionic form, medronate;   neridronic acid or its ionic form, neridronate;   olpadronic acid or its ionic form, olpadronate;   pamidronic acid or its ionic form, pamidronate;   risedronic acid or its ionic form, risedronate;   tiludronic acid or its ionic form, tiludronate;   zoledronic (or zolendronic) acid or its ionic form, zoledronate (or zolendronate)   4-N,N-dimethylaminomethane diphosphonic acid or its ionic form, dimethylaminomethanediphosphonate;   α-amino-(4-hydroxybenzylidene)diphosphonate.   
     
     
         20 . Process according to  claim 14 , in which the farnesyl-pyrophosphate synthase inhibitor is zoledronic acid or its ionic form, zoledronate. 
     
     
         21 . Process according to  claim 14 , in which the administration is performed with a dose of the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor of 0.01 to 2 mg/kg of body weight and with a dose of the farnesyl-pyrophosphate synthase inhibitor of 0.01 to 40 mg/kg of body weight. 
     
     
         22 . Process according to  claim 14 , in which the administration is performed orally or by injection. 
     
     
         23 . Process for treating an HIV-infected patient comprising, in any order, the following steps:
 i. administration of a mixture comprising at least one hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor and at least one farnesyl-pyrophosphate synthase inhibitor,   ii. administration of an anti-HIV agent, in which the administrations are concomitant, successive or alternative.   
     
     
         24 . Process according to  claim 23 , in which said mixture and said anti-HIV agent are co-administered. 
     
     
         25 . Process according to  claim 23 , in which the anti-HIV agent is a protease inhibitor or a reverse transcriptase inhibitor. 
     
     
         26 . Process according to  claim 23 , in which the anti-HIV agent is a protease inhibitor chosen from the group comprising fosamprenavir, lopinavir, ritonavir, amprenavir, atazanavir and indinavir. 
     
     
         27 . Process according to  claim 23 , in which the anti-HIV agent is a reverse transcriptase inhibitor chosen from the group comprising zidovudine, lamivudine, didanosine and epzicom. 
     
     
         28 . Process according to  claim 23 , in which at least one of the administrations is performed orally or by injection. 
     
     
         29 . Process according to  claim 23 , in which the administration is performed with a dose of the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor of 0.01 to 2 mg/kg of body weight and with a dose of the farnesyl-pyrophosphate synthase inhibitor of 0.01 to 40 mg/kg of body weight.