Methods of preventing hiv infections in humans

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 human subject from being infected with human immunodeficiency virus 1 (HIV-1), by:   (a) orally administering a daily dose of a formulation to a human subject, wherein the human subject has been tested for the presence of HIV-1 and is known to be serologically negative for HIV-1 prior to the first oral administration, wherein at least some of the administering occurs before the human subject is first exposed to HIV-1 following the test for the presence of HIV-1, the formulation comprising:
 i. a therapeutically effective amount of a tenofovir prodrug; and 
 ii. emtricitabine in an amount of 200 mg, wherein the oral administration results in an area under the plasma concentration-time curve (AUC) of emtricitabine over a 24 hour interval of 10.0±3.12 μg-hr/mL; and 
   (b) testing the blood serum of the human subject for the presence of HIV-1 after a period of orally administering the daily dose for several days, weeks, or months, wherein the daily dose prohibits the human subject from becoming infected with HIV-1.   
     
     
         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 the tenofovir prodrug is a tenofovir ester. 
     
     
         4 . The method of  claim 1 , wherein the human subject is exposed to HIV-1 via a needle subsequent to at least some of the oral administration of the daily dose of the formulation. 
     
     
         5 . The method of  claim 1 , wherein the human subject is sexually exposed to HIV-1 subsequent to at least some of the oral administration of the daily dose of the formulation. 
     
     
         6 . The method of  claim 1 , wherein the oral administration of the daily dose of the formulation results in an absence of persistent viremia or HIV-1 seroconversion in the human subject following exposure to HIV-1. 
     
     
         7 . The method of  claim 1 , wherein the method results in the human subject being protected from developing a sexually acquired HIV-1 infection. 
     
     
         8 . The method of  claim 1 , wherein the oral administration of the daily dose occurs for several months. 
     
     
         9 . The method of  claim 1 , wherein the oral administration of the daily dose continues through a period where the human subject is subjected to multiple potential exposures of HIV-1. 
     
     
         10 . The method of  claim 1 , wherein the oral administration of the daily dose occurs for several days. 
     
     
         11 . A pre-exposure prophylactic method, comprising:
 protecting a human subject from being infected with human immunodeficiency virus 1 (HIV-1) by orally administering a daily dose of a formulation to a human subject who is known to be HIV-1 negative, wherein the first administration occurs before the human subject is exposed to HIV-1 through sexual activity, and wherein the formulation comprises a therapeutically effective amount of:
 i. tenofovir or a tenofovir prodrug; and 
 ii. emtricitabine, wherein the oral administration results in an area under the plasma concentration-time curve (AUC) of emtricitabine over a 24 hour interval of 10.0±3.12 μg-hr/mL, and wherein the human subject is prevented from becoming infected with HIV-1 following sexual activity with an HIV-1 infected person. 
   
     
     
         12 . The method of  claim 11 , wherein the formulation is compounded as a single formulation comprising (i) and (ii). 
     
     
         13 . The method of  claim 11 , wherein the formulation is in a tablet form. 
     
     
         14 . The method of  claim 11 , wherein the formulation comprises tenofovir disoproxil fumarate in an amount of 300 mg. 
     
     
         15 . The method of  claim 11 , wherein the formulation comprises a tenofovir ester. 
     
     
         16 . The method of  claim 11 , wherein oral administration is a single tablet of the formulation taken daily by the human subject. 
     
     
         17 . The method of  claim 11 , wherein prior to the oral administration the human subject is tested for the presence of a HIV-1 viral genome. 
     
     
         18 . The method of  claim 17 , wherein the test for the presence of a HIV-1 viral genome is a polymerase chain reaction assay. 
     
     
         19 . The method of  claim 17 , wherein the formulation is orally administered daily for several months, and wherein the subject is tested for HIV-1 infection after several months of receiving the daily oral administration of the formulation. 
     
     
         20 . A method, comprising:
 (a) confirming that a human subject has not been infected with HIV-1;   (b) following confirmation that the human subject has not been infected with the HIV-1 and before the human subject is exposed to HIV-1, orally administering a therapeutically effective amount of a formulation comprising:
 i. a therapeutically effective amount of a tenofovir prodrug; and 
 ii. emtricitabine in an amount of 200 mg, wherein the oral administration results in an area under the plasma concentration-time curve (AUC) of emtricitabine over a 24 hour interval of 10.0±3.12 μg-hr/mL; 
   (c) continuing to orally administer the formulation to the human subject while the subject is at risk for being exposed to HIV-1; and   (d) confirming that the human subject remains seronegative for HIV-1 after several months of oral administration by testing the human subject for the presence of a HIV-1 infection.   
     
     
         21 . The method of  claim 20 , wherein the tenofovir prodrug is tenofovir disoproxil fumarate in an amount of 300 mg. 
     
     
         22 . The method of  claim 20 , wherein the tenofovir prodrug is a tenofovir ester. 
     
     
         23 . The method of  claim 22 , wherein the oral administration of the daily dose occurs for several months. 
     
     
         24 . The method of  claim 23 , comprising testing the human subject for a self-replicating HIV-1 infection following the several months of daily doses of the formulation. 
     
     
         25 . The method of  claim 23 , wherein the formulation is continuously administered through a period where the human subject is subjected to multiple potential exposures of HIV-1 and the administration continues to inhibit the human subject from developing an HIV-1 infection. 
     
     
         26 . The method of  claim 22 , wherein oral administration in step (b) is to a human subject who is known to not have been sexually exposed to HIV-1. 
     
     
         27 . The method of  claim 22 , wherein confirming that the human subject has not been infected with a HIV-1 virus comprises testing for the presence of a HIV-1 viral genome in the human subject's serum or plasma. 
     
     
         28 . The method of  claim 27 , wherein the test for the presence of the HIV-1 viral genome is a polymerase chain reaction assay. 
     
     
         29 . The method of  claim 22 , wherein the oral administration of the daily dose of the formulation results in an absence of persistent viremia and HIV-1 seroconversion in the human subject. 
     
     
         30 . The method of  claim 22 , wherein the method results in the human subject being protected from developing a sexually acquired HIV-1 infection. 
     
     
         31 . A kit comprising an effective amount of a formulation for oral administration, wherein the formulation comprises:
 i) a therapeutically effective amount of a tenofovir prodrug; and   ii) emtricitabine in an amount of 200 mg,   for use in the method of  claim 1 .