Pre-exposure prophylaxis of hiv infections

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 of prohibiting a human subject uninfected with immunodeficiency virus 1 (HIV-1) from becoming seropositive for a self-replicating HIV-1 infection, comprising:
 (a) confirming that a human subject is not infected with HIV-1;   (b) starting the human subject on a pre-exposure prophylaxis treatment regimen of daily oral doses of a tablet comprising:
 i. emtricitabine in an amount of 200 mg; and 
 ii. a pharmaceutically effective amount of a tenofovir prodrug; and 
   (c) continuing the treatment regimen for several days or months so the human subject, while being treated, does not develop a self-replicating HIV-1 infection following exposure to a HIV-1 virus.   
     
     
         2 . The method of  claim 1 , wherein the tenofovir prodrug is a tenofovir ester. 
     
     
         3 . The method of  claim 1 , wherein the tenofovir prodrug is tenofovir disoproxil fumarate in an amount of 300 mg. 
     
     
         4 . The method of  claim 1 , wherein the daily oral doses of the tablet result in steady-state plasma levels of the emtricitabine and tenofovir in the human subject. 
     
     
         5 . The method of  claim 1 , wherein the treatment regimen results in an area under the plasma concentration time curve (AUC) for emtricitabine over 24 hours of 11 μg·hr/mL. 
     
     
         6 . The method of  claim 1 , wherein the treatment regimen results in an area under the plasma concentration time curve (AUC) for emtricitabine over 24 hours of 10±3.12 μg·hr/mL. 
     
     
         7 . The method of  claim 1 , wherein continuing the treatment regimen results in an absence of persistent viremia or HIV-1 seroconversion. 
     
     
         8 . The method of  claim 1 , wherein continuing the treatment regimen protects the human subject from a sexually acquired HIV-1 self-replicating infection. 
     
     
         9 . The method of  claim 1 , wherein the treatment regimen continues through a period where the human subject is subjected to multiple potential exposures of HIV-1. 
     
     
         10 . The method of  claim 1 , further comprising testing the blood serum of the human subject to confirm the absence of a self-replicating HIV-1 infection during the several months. 
     
     
         11 . A method, comprising:
 inhibiting a primate subject who has not been exposed to an immunodeficiency retrovirus from becoming infected with the immunodeficiency retrovirus following exposure, comprising:   (a) testing the primate subject to determine if the subject has a detectable immunodeficiency retrovirus infection;   (b) placing the primate subject on a treatment regimen of daily oral doses of a composition if the primate subject does not have a detectable immunodeficiency retrovirus infection, wherein the composition comprises:
 i. emtricitabine in an amount of 200 mg; and 
 ii. a therapeutically effective amount of a tenofovir prodrug; and 
   continuing the treatment regimen to continue inhibiting the primate subject from developing a self-replicating immunodeficiency retrovirus infection following one or more exposures to the immunodeficiency retrovirus.   
     
     
         12 . The method of  claim 11 , wherein the tenofovir prodrug is a tenofovir ester. 
     
     
         13 . The method of  claim 11 , wherein the treatment regimen results in an area under the plasma concentration time curve (AUC) for emtricitabine over 24 hours of 6.88 μg·hr/mL to about 13.12 μg·hr/mL. 
     
     
         14 . The method of  claim 11 , wherein continuing the treatment regimen results in the primate subject being protected from a sexually acquired immunodeficiency retrovirus self-replicating infection. 
     
     
         15 . The method of  claim 11 , wherein the treatment regimen comprises daily oral doses of a tablet comprising 200 mg emtricitabine and 300 mg of tenofovir disoproxil fumarate. 
     
     
         16 . The method of  claim 15 , wherein the daily oral doses of the tablet results in a persistent viremia or immunodeficiency retrovirus seroconversion being inhibited from developing in the primate subject. 
     
     
         17 . The method of  claim 16 , further comprising testing the subject after several months of the treatment regimen for the absence of a self-replicating infection to confirm that an immunodeficiency retrovirus infection has not occurred in the primate subject. 
     
     
         18 . The method of  claim 11 , wherein the treatment regimen comprises daily oral doses of a tablet comprising a tenofovir ester. 
     
     
         19 . The method of  claim 18 , wherein the daily oral doses of the tablet results in an absence of persistent viremia and immunodeficiency retrovirus seroconversion in the subject. 
     
     
         20 . The method of  claim 11 , wherein inhibiting the primate subject who has not been exposed to an immunodeficiency retrovirus from becoming infected comprises testing the primate subject following the one or more exposures to the immunodeficiency retrovirus to confirm that the primate subject continues to lack a detectable immunodeficiency retrovirus infection. 
     
     
         21 . The method of  claim 11 , wherein the primate subject is an adult human subject and the immunodeficiency retrovirus is human immunodeficiency virus 1 (HIV-1). 
     
     
         22 . The method of  claim 21 , wherein the method protects the human subject from a sexually acquired HIV-1 infection. 
     
     
         23 . A method comprising:
 (a) prohibiting a human immunodeficiency virus 1 (HIV-1) uninfected human subject from becoming infected with a HIV-1 virus by starting the uninfected human subject on a treatment regimen of daily oral doses of a tablet comprising:
 i. emtricitabine in an amount of 200 mg; and 
 ii. a pharmaceutically effective amount of a tenofovir prodrug; 
   wherein the treatment regimen starts before an exposure to HIV-1; and   (b) treating the uninfected human subject for several months with daily oral doses of the tablet to continue prohibiting the human subject from developing a self-replicating HIV-1 infection if the human subject is exposed to the HIV-1 virus one or more times during the several months.   
     
     
         24 . The method of  claim 23 , wherein the tenofovir prodrug is a tenofovir ester. 
     
     
         25 . The method of  claim 23 , wherein the tenofovir prodrug is tenofovir disoproxil fumarate. 
     
     
         26 . The method of  claim 25 , wherein the tenofovir disoproxil fumarate is 300 mg of tenofovir disoproxil fumarate. 
     
     
         27 . The method of  claim 23 , wherein the treatment regimen results in an area under the plasma concentration time curve (AUC) for emtricitabine over 24 hours of 6.88 μg·hr/mL to about 13.12 μg·hr/mL. 
     
     
         28 . The method of  claim 27 , wherein the human subject is protected from a sexually acquired HIV-1 self-replicating infection during the several months of treatment. 
     
     
         29 . The method of  claim 28 , wherein the daily oral doses of the tablet results in an absence of persistent viremia and HIV-1 seroconversion in the human subject over the several months. 
     
     
         30 . The method of  claim 29 , comprising testing the human subject after the several months to confirm that the human subject did not develop a self-replicating HIV-1 infection. 
     
     
         31 . A composition comprising:
 a) emtricitabine in an amount of 200 mg; and   b) a pharmaceutically effective amount of a tenofovir prodrug for use in a method of prohibiting a human subject uninfected with immunodeficiency virus 1 (HIV-1) from becoming seropositive for a self-replicating HIV-1 infection, comprising:   i) confirming that a human subject is not infected with HIV-1;   ii) starting the human subject on a pre-exposure prophylaxis treatment regimen of daily oral doses of a tablet comprising the composition; and   iii) continuing the treatment regimen for several days or months so the human subject, while being treated, does not develop a self-replicating HIV-1 infection following exposure to a HIV-1 virus.