Means and methods for monitoring non-nucleoside reverse transcriptase inhibitor antiretroviral therapy and guiding therapeutic decisions in the treatment of HIV/AIDS
View Patent ↗This invention relates to antiviral drug susceptibility and resistance tests to be used in identifying effective drug regimens for the treatment of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) and further relates to the means and methods of monitoring the clinical progression of HIV infection and its response to antiretroviral therapy, particularly non-nucleoside reverse transcriptase inhibitor therapy using phenotypic susceptibility assays or genotypic assays.
1. A method of assessing the effectiveness of a non nucleoside reverse transcriptase inhibitor (“NNRTI”) on an HIV-1-infected patient, comprising: detecting, in a biological sample of the HIV-1-infected patient, the presence of a nucleic acid that exhibits a mutation at codon 230 of a nucleotide sequence encoding HIV-1 reverse transcriptase, wherein the presence of such a mutation correlates with a decrease in susceptibility to delavirdine or nevirapine.
2. The method of claim 1 , wherein the presence of the mutation at codon 230 correlates with a decrease in susceptibility to delavirdine and nevirapine.
3. The method of claim 1 , wherein the presence of the mutation at codon 230 correlates with a decrease in susceptibility to delavirdine.
4. The method of claim 1 , wherein the presence of the mutation at codon 230 correlates with a decrease in susceptibility to nevirapine.
5. The method of claim 1 , wherein the mutation at codon 230 encodes a leucine (L).
6. The method of claim 1 , further comprising evaluating whether the biological sample of the HIV-1-infected patient comprises a nucleic acid encoding HIV-1reverse transcriptase having a mutation at codon 181.
7. The method of claim 6 , wherein the mutation at codon 181 encodes a cysteine (C).
8. The method of claim 1 , wherein the HIV-1-infected patient is being treated with an antiretroviral agent.
9. A method of assessing the effectiveness of a non nucleoside reverse transcriptase inhibitor (“NNRTI”) on an HIV-1-infected patient comprising detecting, in a biological sample of the HIV-1-infected patient, the presence of a mutation at codon 181 of the nucleic acid encoding HIV-1 reverse transcriptase, wherein the presence of such a mutation correlates with a decrease in susceptibility to delavirdine or nevirapine and little or no change in susceptibility to efavirenz.
10. The method of claim 9 , wherein the presence of the mutation at codon 181 correlates with a decrease in susceptibility to delavirdine and nevirapine and little or no change in susceptibility to efavirenz.
11. The method of claim 9 , wherein the presence of the mutation at codon 181 correlates with a decrease in susceptibility to delavirdine and little or no change in susceptibility to efavirenz.
12. The method of claim 9 , wherein the presence of the mutation at codon 181 correlates with a decrease in susceptibility to nevirapine and little or no change in susceptibility to efavirenz.
13. The method of claim 9 , wherein the mutation at codon 181 codes for a cysteine (C).
14. The method of claim 9 , further comprising evaluating whether the biological sample of the HIV-1-infected patient comprises nucleic acid encoding HIV-1 reverse transcriptase having a mutation at at least one of codon 98, codon 106 or codon 227.
15. The method of claim 14 , wherein the mutation at codon 98 encodes a glycine (G).
16. The method of claim 14 , wherein the mutation at codon 106 encodes an alanine (A).
17. The method of claim 14 , wherein the mutation at codon 227 encodes a leucine (L).
18. The method of claim 14 , wherein the mutation at codon 98 encodes a glycine (G); the mutation at codon 106 encodes an alanine (A); and the mutation at codon 227 encodes a leucine (L).
19. The method of claim 9 wherein the HIV-1-infected patient is being treated with an antiretroviral agent.