Novel hiv-1 reverse transcriptase codon deletion and its use in the management and treatment of hiv infections

Abstract

The present invention provides an isolated HIV-1 mutant and isolated nucleic acid molecules comprising HIV-RT coding sequences harboring a novel mutation in the S68 codon, and in particular, deletions of the S68 codon. This novel deletion reduces the sensitivity of HIV to various nucleoside reverse transcriptase inhibitors. Methods of using this mutation for selecting effective antiretroviral agents in vitro and in vivo, methods for monitoring infection progression in HIV-infected individuals and methods for avoiding the emergence of and/or to treat individuals infected with HIV comprising mutations, including deletions, at the S68 codon of HIV-RT are provided.

1 - 10 . (canceled) 
     
     
         11 . A method of treating an HIV-infected individual with an effective antiretroviral therapy, comprising:
 (i) collecting lymphocytic cells from an HIV-infected individual;   (ii) determining whether the cells comprise nucleic acid encoding HIV-RT sequences comprising a codon 68 deletion,   wherein if HIV-RT sequences comprising a codon 68 deletion are present, an antiretroviral therapy is selected which inhibits production of HIV-RT codon 68 deletion variant RNA in the cells; and   (iii) administering to the individual the selected antiretroviral therapy.   
     
     
         12 . The method of  claim 11 , wherein if the HIV-infected individual was undergoing an antiretroviral treatment prior to step (i), the treatment is altered based on the determination step (ii). 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 12 , wherein the alteration of treatment comprises administering at least one antiretroviral agent that reduces or eliminates RNA production by the HIV variant having a codon 68 deletion. 
     
     
         15 . The method of  claim 14 , wherein the codon 68 deletion removes AGT of codon 68 or GTA spanning codons 68 and 69. 
     
     
         16 . The method of  claim 14 , wherein the at least one antiretroviral agent is selected from the group consisting of a protease inhibitor, a non-nucleoside reverse transcriptase inhibitor, an HIV fusion inhibitor, an HIV integrase inhibitor, an RNAse H inhibitor, a CD4 binding inhibitor, a CXCR4 binding inhibitor and a CCR5 binding inhibitor. 
     
     
         17 . The method of  claim 14 , wherein the at least one antiretroviral agent is selected from the group consisting of AZT, DDI, DFDOC, D4T, DOT and DDC. 
     
     
         18 . The method of  claim 11 , wherein the absence of or decreasing concentrations of detectable HIV sequences correlates positively with the assessment that the antiretroviral agent is therapeutically effective in treating the codon 68 mutant HIV. 
     
     
         19 - 42 . (canceled)