Methods of inhibiting hiv infections by pre-exposure prophylaxis

Abstract

A process is provided for protecting a primate host from a self-replicating infection by an immunodeficiency retrovirus. Protection is achieved by administering to the primate host a combination of a pharmaceutically effective amount of a nucleoside reverse transcriptase inhibitor and a pharmaceutically effective amount of a nucleotide reverse transcriptase inhibitor prior to exposure to the immunodeficiency retrovirus. The administration is effective if provided in a single dose within 24 hours of the exposure. A regime of regular daily doses is also effective in providing protection against an immunodeficiency retrovirus becoming self-replicating after infecting a primate host. A process for controlling retrovirus transmission within a population includes the administration to a subpopulation at high risk for contracting an immunodeficiency retroviral infection the detailed combination prior to sexual exposure to a source of immunodeficiency retrovirus so as to preclude the immunodeficiency retrovirus from becoming self-replicating in a member of the subpopulation.

1 . A method, comprising:
 prohibiting a primate subject from acquiring an immunodeficiency retrovirus infection by:   a. determining if the primate subject is negative for a detectable immunodeficiency retrovirus infection; and   b. orally administering a plurality of doses of at least one tablet comprising 200 mg emtricitabine (FTC) and a pharmaceutically effective amount of a tenofovir prodrug to the subject if the primate subject is negative for the immunodeficiency retrovirus infection, wherein at least a first dose occurs before the primate subject is potentially exposed to the immunodeficiency retrovirus; and   testing the primate subject after the oral administration to confirm that the subject has remained negative for the detectable immunodeficiency retrovirus infection following a plurality of doses.   
     
     
         2 . The method of  claim 1 , wherein the tenofovir prodrug is tenofovir disoproxil fumarate in an amount of 300 mg. 
     
     
         3 . The method of  claim 1 , wherein orally administering the at least one tablet comprises orally administering one tablet per day. 
     
     
         4 . The method of  claim 1 , wherein the tenofovir prodrug comprises a tenofovir ester. 
     
     
         5 . The method of  claim 1 , wherein the oral administration of the at least one tablet results in an area under the plasma concentration-time curve (AUC) over a 24 hour interval for emtricitabine in the primate subject of 6.88 μg·hr/mL to 13.12 μg·hr/mL. 
     
     
         6 . The method of  claim 1 , wherein the oral administration of the at least one tablet results in an area under the plasma concentration-time curve (AUC) over a 24 hour interval for emtricitabine in the primate subject of 11 μg·hr/mL. 
     
     
         7 . The method of  claim 1 , wherein the testing the primate subject comprises a polymerase chain reaction (PCR) assay to detect the presence of the immunodeficiency retroviral genome in the primate subject. 
     
     
         8 . The method of  claim 1 , wherein the oral administration of the at least one tablet results in an absence of an immunodeficiency retrovirus seroconversion in the primate subject. 
     
     
         9 . The method of  claim 1 , wherein the primate subject is an adult human subject. 
     
     
         10 . The method of  claim 1 , wherein the oral administration of the plurality of doses of the at least one tablet comprises a treatment regimen over a time period, and wherein the testing of the primate subject occurs regularly during the time period of the treatment regimen. 
     
     
         11 . The method of  claim 1 , wherein the oral administration of the plurality of doses of the at least one tablet prohibits a subsequent HIV-1 exposure of the primate subject from becoming a self-replicating HIV-1 infection. 
     
     
         12 . A method, comprising
 inhibiting a human subject who is uninfected with human immunodeficiency virus 1 (HIV-1) from becoming infected, by:
 a. screening the human subject to confirm that the subject does not have a detectable HIV-1 infection; 
 b. orally administering a plurality of doses of at least one tablet comprising 200 mg emtricitabine (FTC) and a pharmaceutically effective amount of a prodrug of tenofovir to the subject if the primate subject is confirmed to not have an HIV-1 infection, wherein the administration occurs before the human subject is exposed to HIV-1; and 
 c. testing the human after the subject has been potentially exposed to HIV-1 to confirm that the human subject does not have an HIV-1 infection. 
   
     
     
         13 . The method of  claim 12 , wherein the prodrug of tenofovir is tenofovir disoproxil fumarate in an amount of 300 mg. 
     
     
         14 . The method of  claim 12 , wherein the prodrug of tenofovir is a tenofovir ester. 
     
     
         15 . The method of  claim 12 , wherein administration of a single dose of the tablet results in an area under the plasma concentration-time curve (AUC) for emtricitabine of about 6.88 μg·hr/mL to about 13.12 μg·hr/mL. 
     
     
         16 . The method of  claim 12 , wherein administration of a single dose of the tablet results in an area under the plasma concentration-time curve (AUC) for emtricitabine of 11 μg·hr/mL. 
     
     
         17 . The method of  claim 12 , wherein the oral administration is a daily oral dose of the tablet. 
     
     
         18 . The method of  claim 17 , wherein the daily oral dose of the tablet inhibits a subsequent HIV-1 exposure of the human subject from becoming a self-replicating HIV-1 infection. 
     
     
         19 . The method of  claim 17 , wherein the daily oral dose of the tablet is administered daily for several months, and wherein the subject is tested for HIV-1 infection during the course of the several months of administration. 
     
     
         20 . The method of  claim 19 , wherein the daily oral dose of the tablet results in steady-state plasma levels of emtricitabine and tenofovir in the primate subject. 
     
     
         21 . A pre-exposure prophylactic treatment method for preventing an exposure of a human subject to human immunodeficiency virus 1 (HIV-1) from becoming a HIV-1 self-replicating infection, comprising:
 a. confirming that the human subject is serologically negative for HIV-1;   b. orally administering a plurality of daily doses of a tablet comprising 200 mg emtricitabine (FTC) and a pharmaceutically effective amount of a tenofovir prodrug to the human subject if the human subject is serologically negative for HIV-1, wherein the administration is initiated before the human subject has been exposed to HIV-1; and   c. testing the human subject after several months of the oral administration to confirm that the subject does not have a self-replicating HIV-1 infection.   
     
     
         22 . The treatment method of  claim 21 , wherein the tenofovir prodrug is tenofovir disoproxil fumarate in an amount of 300 mg. 
     
     
         23 . The treatment method of  claim 21 , wherein the tenofovir prodrug is a tenofovir ester. 
     
     
         24 . The treatment method of  claim 23 , wherein if the testing determines that the subject does not have a self-replicating HIV-1 infection after the several months of daily doses of the tablet, then continuing with the daily doses of the tablet. 
     
     
         25 . The method of  claim 23 , wherein the oral administration of the daily doses of the tablet results in the human subject being protected from developing a self-replicating HIV-1 infection following sexual exposure to an HIV-1-infected subject. 
     
     
         26 . A pre-exposure prophylactic treatment method for preventing an exposure of a human subject to human immunodeficiency virus 1 (HIV-1) from becoming a HIV-1 self-replicating infection, comprising:
 a. confirming that the human subject is negative for an HIV-1 infection;   b. orally administering a daily dose of a tablet comprising 200 mg emtricitabine (FTC) and a tenofovir prodrug to the human subject for several months if the human subject is serologically negative for HIV-1; and   c. testing the human subject after the several months of the oral administration to confirm that the human subject has not developed a self-replicating retroviral infection.   
     
     
         27 . The method of  claim 26 , wherein the tenofovir prodrug is tenofovir disoproxil fumarate in an amount of 300 mg. 
     
     
         28 . The method of  claim 26 , wherein the tenofovir prodrug is a tenofovir ester. 
     
     
         29 . The method of  claim 26 , wherein the oral administration of the tablet results in an area under the plasma concentration-time curve (AUC) over a 24 hour interval for emtricitabine in the human subject of 10.0±3.12 μg·hr/mL. 
     
     
         30 . The method of  claim 26 , wherein the oral administration of the tablet results in an area under the plasma concentration-time curve (AUC) over a 24 hour interval for emtricitabine in the human subject of 11 μg·hr/mL. 
     
     
         31 . A kit, comprising a plurality of doses of a tablet comprising 200 mg emtricitabine (FTC) and a pharmaceutically effective amount of a tenofovir prodrug, for use in the method of  claim 1 .