Treatments to eliminate hiv reservoirs and reduce viral load

Abstract

The present invention relates to a compound inducing activation of HLA-E-restricted CD8 T cells and/or NK cells in a human subject, and reducing HIV viral load, such as glatiramer acetate and glatiramer acetate related active substances and products, for use in the treatment of HIV infection. Macaques chronically infected by SIV have been treated with glatiramer acetate. One of the animals had already progressed to the stage of AIDS. We injected 18 mg of glatiramer acetate three times per week for only 2 weeks. Surprisingly, a strong impact on viral load was observed in response to the treatment. Viremia decreased by 1 log during glatiramer acetate treatment. Even more surprising was the fact that this decrease persisted after stopping the treatment reaching almost a 2 logs decrease in one animal. This is a major result as compared to cART as stopping cART leads to a rebound of the viral load within days. This decrease was correlated with activation of HLA-E restricted CD8 T cells, but not to other classical CD8+ T cells.

1 . A method for detecting the presence or absence of HIV-1-specific nucleic acid comprising:
 a) administering a dose of glatiramer acetate to an HIV-1-infected patient,   b) taking a blood sample from the patient;   c) preparing RNA from the blood sample;   d) preparing cDNA from the RNA;   e) amplifying the cDNA by making DNA or RNA copies thereof to generate an amplified sample; and   f) detecting the presence or absence of HIV-1-specific nucleic acid in the amplified sample.   
     
     
         2 - 20 . (canceled) 
     
     
         21 . A kit of parts for simultaneous, separate, or sequential administration to an HIV-infected patient comprising an effective amount of glatiramer acetate and an HIV inhibitor. 
     
     
         22 . The kit of parts of  claim 21 , comprising at least 2 additional HIV inhibitors. 
     
     
         23 . The kit of parts of  claim 21 , comprising at least 2 of any of the following compounds:
 lamivudine; zidovudine; lopinavir; ritonavir; abacavir; tenofovir disoproxil fumarate; emtricitabine; efavirenz; rilpivirine; elvitegravir; cobicistat; dolutegravir; atazanavir; cobicistat; darunavir; and raltegravir.   
     
     
         24 . The kit of parts of  claim 21 , wherein the HIV inhibitor comprises a Rev inhibitor. 
     
     
         25 . The kit of parts of  claim 21 , wherein the HIV inhibitor comprises 8-chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-am ine (ABX464) and 8-chloro-N-glucuronide-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine) (ABX464-N-glucuronide). 
     
     
         26 . The kit of parts of  claim 21 , wherein the HIV inhibitor comprises 8-chloro-N-(4-(trifluoromethoxy)phenyl)quinolin-2-am ine (ABX464) and 8-chloro-N-glucuronide-N-(4-(trifluoromethoxy)phenyl)quinolin-2-amine) (ABX464-N-glucuronide) and cART comprising at least 2 or 3 of any of the following compounds:
 lamivudine; zidovudine; lopinavir; ritonavir; abacavir; tenofovir disoproxil fumarate; emtricitabine; efavirenz; rilpivirine; elvitegravir; cobicistat; dolutegravir; atazanavir; cobicistat; darunavir; and raltegravir.   
     
     
         27 . The kit of parts of  claim 21 , comprising lam ivudine+zidovudine. 
     
     
         28 . The kit of parts of  claim 21 , comprising lopinavir+ritonavir 
     
     
         29 . The kit of parts of  claim 21 , comprising abacavir+lam ivudine+zidovudine 
     
     
         30 . The kit of parts of  claim 21 , comprising abacavir+lam ivudine. 
     
     
         31 . The kit of parts of  claim 21 , comprising tenofovir disoproxil fumarate+emtricitabine. 
     
     
         32 . The kit of parts of  claim 21 , comprising emtricitabine+tenofovir disoproxil fumarate+efavirenz 
     
     
         33 . The kit of parts of  claim 21 , comprising emtricitabine+rilpivirine+tenofovir disoproxil fumarate. 
     
     
         34 . The kit of parts of  claim 21 , comprising elvitegravir+cobicistat+emtricitabine+tenofovir disoproxil fumarate. 
     
     
         35 . The kit of parts of  claim 21 , comprising abacavir+dolutegravir+lam ivudine. 
     
     
         36 . The kit of parts of  claim 21 , comprising atazanavir+cobicistat. 
     
     
         37 . The kit of parts of  claim 21 , comprising darunavir+cobicistat. 
     
     
         38 . The kit of parts of  claim 21 , comprising lam ivudine+raltegravir. 
     
     
         39 . The kit of parts of  claim 21 , comprising elvitegravir+cobicistat+emtricitabine+tenofovir alafenamide fumarate. 
     
     
         40 . The kit of parts of  claim 21 , comprising emtricitabine+tenofovir alafenamide fumarate. 
     
     
         41 . The kit of parts of  claim 21 , comprising a 20 mg dose of glatiramer acetate. 
     
     
         42 . The kit of parts of  claim 21 , comprising a 40 mg dose of glatiramer acetate. 
     
     
         43 . The kit of parts of  claim 23 , comprising a 20 mg dose of glatiramer acetate. 
     
     
         44 . The kit of parts of  claim 23 , comprising a 40 mg dose of glatiramer acetate.