Treatment agents for inhibiting hiv and cancer in hiv infected patients

Abstract

Methods are provided for treating HIV and cancer in a subject in need thereof by administering to the subject therapeutically effective amounts of an mTOR inhibitor. Other methods are provided for treating subjects infected with HIV by administering to the subject therapeutically effective amounts of the mTOR inhibitor INK128, GSK2126458, AZD2014 or Torin-2.

What is claimed is: 
     
         1 . A method of treating Human Immunodeficiency Virus and cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an mTOR inhibitor. 
     
     
         2 . The method of  claim 1 , wherein the mTOR inhibitor is selected from the group consisting of INK128, GSK2126458, AZD2014, and Torin-2. 
     
     
         3 . The method of  claim 2 , wherein the mTOR inhibitor is INK128 or Torin-2. 
     
     
         4 . The method of  claim 3 , wherein INK128 is administered in a therapeutically effective amount from about 0.5 mg to about 4 mg to achieve a plasma concentration of about 200 nM in the subject. 
     
     
         5 . The method of  claim 3 , wherein Torin-2 is administered in a therapeutically effective amount from 0.05 mg to about 10 mg. 
     
     
         6 . The method of  claim 2  wherein GSK2126458 is administered in a therapeutically effective amount from 0.05 mg to about 0.25 mg. 
     
     
         7 . The method of  claim 2 , wherein AZD2014 is administered in a therapeutically effective amount from 5 mg to about 50 mg. 
     
     
         8 . The method of  claim 2 , wherein the mTOR inhibitor is administered orally, intravenously, intramuscularly, intrathecally, or subcutaneously, sublingually. buccally, rectally, vaginally, by ocular route or by otic route, nasally, by inhalation, by nebulization, cutaneously, topically or systemically, and transdermally. 
     
     
         9 . The method of  claim 2 , wherein the mTOR inhibitor is administered alone, or in combination with a second mTOR inhibitor. 
     
     
         10 . The method of  claim 9 , wherein the mTOR inhibitor is INK128. 
     
     
         11 . The method of  claim 10 , wherein INK128 is administered in combination with Torin-2. 
     
     
         12 . The method of  claim 2 , wherein the mTOR inhibitor is administered alone, or in combination with a second antiretroviral agent. 
     
     
         13 . The method of  claim 12 , wherein the mTOR inhibitor and the second antiretroviral agent are administered at the same time, at different times, or sequentially. 
     
     
         14 . The method of  claim 12 , wherein the second antiretroviral agent is selected from the group consisting of CCR5 antagonists, reverse transcriptase inhibitors, integrase inhibitors, protease inhibitors, and any combination thereof. 
     
     
         15 . The method of  claim 12 , wherein the wherein the mTOR inhibitor and the second antiretroviral agent are administered in combination with a cancer therapeutic agent selected from the group consisting of DNA damaging agents, microtubule agents, and signal transduction agents. 
     
     
         16 . The method of  claim 15 , wherein the cancer therapeutic agents are selected from the group consisting of carboplatin, BCNU, cytosine arabinoside, paclitaxel, vinblastine, sorafenib, pazopanib, erlotinib, and imatinib. 
     
     
         17 . The method of  claim 1 , wherein the cancer is selected from the group consisting of non-small cell lung, small cell lung, prostate, breast, liver, Hodgkin lymphoma, non-Hodgkin lymphoma, Kaposi sarcoma, B cell acute lymphoblastic leukemia, bone sarcoma, and soft tissue sarcoma. 
     
     
         18 . A method of treating Human Immunodeficiency Virus in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a an INK128 having a chemical structure: 
       
         
           
           
               
               
           
         
         or an mTOR inhibitor Torin-2 having a chemical structure: 
       
       
         
           
           
               
               
           
         
         or a salt or hydrate thereof. 
       
     
     
         19 . The method of  claim 18 , wherein INK128 is administered in a therapeutically effective amount from about 0.5 mg to about 4 mg to achieve a plasma concentration of about 200 nM in the subject. 
     
     
         20 . The method of  claim 18 , wherein Torin-2 is administered in a therapeutically effective amount from about 0.05 mg to about 10 mg. 
     
     
         21 . The method of  claim 18 , wherein the mTOR inhibitor is administered alone, or in combination with a second antiretroviral agent. 
     
     
         22 . The method of  claim 21 , wherein the antiretroviral agent is selected from the group consisting of an entry inhibitor, a reverse transcriptase inhibitor, a protease inhibitor and an integrase inhibitor. 
     
     
         23 . The method of  claim 22 , wherein the antiretroviral agent is selected from the group consisting of CCR5 antagonists, reverse transcriptase inhibitors, integrase inhibitors, protease inhibitors and any combination thereof. 
     
     
         24 . The method of  claim 23 , wherein the antiretroviral agents are selected from the group consisting of maraviroc, efavirenz, raltegravir, indinavir, and any combination thereof. 
     
     
         25 . The method of  claim 21 , wherein the mTOR inhibitor and the second antiretroviral agent are administered in combination with a cancer therapeutic agent selected from the group consisting of DNA damaging agents, microtubule agents, and signal transduction agents. 
     
     
         26 . The method of  claim 25 , wherein the cancer therapeutic agents are selected from the group consisting of: carboplatin, BCNU, cytosine arabinoside, paclitaxel, vinblastine, sorafenib, pazopanib, erlotinib, and imatinib. 
     
     
         27 . A method of  claim 1 , wherein the therapeutically effective amount of mTOR inhibitor inhibits both R5 and X4 HIV replication. 
     
     
         28 . A method of  claim 1 , wherein the therapeutically effective amount of mTOR inhibitor inhibits entry of R5 Human Immunodeficiency Virus in vitro. 
     
     
         29 . A method of  claim 1 , wherein the therapeutically effective amount of mTOR inhibitor inhibits LTR gene expression.