Methods for determining hypersusceptibility of HIV-1 to non-nucleoside reverse transcriptase inhibitors
View Patent ↗This invention relates to methods for determining hypersusceptibility of HIV-1 viruses to non-nucleoside reverse transcriptase inhibitors (NNRTIs) based on the viral genotypes. The methods generally comprise detecting, in a gene encoding reverse transcriptase of the HIV-1, the presence of a mutation at codon 65, 69, or 74 alone or in combination with one or more mutations at certain other codons. Combinations of mutations associated with hypersusceptibility to NNRTIs are also disclosed.
1. A method for treating a patient having a human immunodeficiency virus 1 (HIV-1) infection, comprising:
(a) obtaining or having obtained a nucleic acid encoding reverse transcriptase of an HIV-1;
(b) detecting or having detected in the nucleic acid the presence or absence of a mutation at codon 184 in combination with a mutation in codon 74, wherein the codon number of said HIV-1 corresponds to the codon number in the wild type HIV-1 isolate NL4-3, wherein the mutation at codon 184 encodes isoleucine (I) instead of methionine (M), and wherein the mutation at codon 74 encodes valine (V) instead of leucine (L);
(c) determining or having determined that the HIV-1 is hypersusceptible to a non-nucleoside reverse transcriptase inhibitor (NNRTI) if the mutations are present; and
(d) treating the patient with an effective amount of the NNRTI if the HIV-1 is determined to be hypersusceptible to the NNRTI in step (c).
2. The method of claim 1 , further comprising in step b):
detecting or having detected in the nucleic acid the presence or absence of a mutation in at least one of codon 210 or 219, wherein the mutation at codon 210 encodes tryptophan (W) instead of leucine (L), and wherein the mutation at codon 219 encodes glutamic acid (E), histidine (H), asparagine (N), glutamine (Q), or arginine (R) instead of lysine (K).
3. The method of claim 1 , wherein the NNRTI is efavirenz (EFV), nevirapine (NVP), or delavirdine (DLV).
4. The method of claim 1 , wherein the NNRTI is EFV.
5. The method of claim 1 , wherein the NNRTI is NVP.
6. The method of claim 1 , wherein the NNRTI is DLV.
7. The method of claim 1 , further comprising in step b):
detecting or having detected in the nucleic acid the presence or absence of a mutation at codon 69, wherein the mutation at codon 69 encodes alanine (A), aspartic acid (D), asparagine (N), or serine (S), instead of threonine (T).
8. The method of claim 1 , further comprising in step b):
detecting or having detected in the nucleic acid the presence or absence of a mutation in at least one of codon 41, 67, 70, and 215, wherein the mutation at codon 41 encodes leucine (L) instead of methionine (M), the mutation at codon 67 encodes asparagine (N) instead of aspartic acid (D), the mutation at codon 70 encodes arginine (R) instead of lysine (K), and the mutation at codon 215 encodes tyrosine (Y) instead of threonine (T).
9. The method of claim 8 , wherein a mutation at codon 41 is detected.
10. The method of claim 8 , wherein a mutation at codon 67 is detected.
11. The method of claim 8 , wherein a mutation at codon 70 is detected.
12. The method of claim 8 , wherein a mutation at codon 215 is detected.