METHODS AND COMPOSITIONS FOR DETERMINING RESISTANCE OF HIV-1 TO PROTEASE INHIBITORS
This invention relates to methods for determining resistance of HIV-I viruses to protease inhibitors (PIs) based on the viral genotypes. The methods generally comprise detecting, in a gene encoding protease of the HIV-I, the presence of a mutation in at least one of codon 22, 69, 74, or 83 alone or in combination with one or more mutations at certain other codons, or, in a gene encoding gag of the HIV-I, the present of a mutation in at least one of codon 418 or 482 alone or in combination with one or more mutations at certain other codons. Combinations of mutations associated with resistance to PIs are also disclosed.
1 . A method for determining whether an HIV-1 is resistant to a PI, comprising detecting whether a mutation in at least one of codon 22, 69, 74, or 83 is present in a gene encoding protease of the HIV-1, wherein the presence of the mutation correlates with resistance to a PI, thereby determining whether the HIV-1 is resistant to the PI.
2 . The method of claim 1 , further comprising detecting whether a mutation in at least one of codon 10, 13, 19, 20, 36, 37, 54, 71, 73, 82, 88, or 93 is present in the gene encoding protease of the HIV-1 in combination with the mutation in at least one of codon 22, 69, 74, or 83, wherein the presence of the mutations correlates with resistance to a PI, thereby determining whether the HIV-1 is resistant to the PI.
3 . The method of claim 1 , further comprising detecting whether a mutation in at least one of codon 23, 24, 30, 32, 46, 47, 48, 50, 54, 82, 84, 88, or 90 is present in the gene encoding protease of the HIV-1 in combination with the mutation in at least one of codon 22, 69, 74, or 83, wherein the presence of the mutations correlates with resistance to a PI, thereby determining whether the HIV-1 is resistant to the PI.
4 . The method of claim 1 , wherein the mutation at codon 22 encodes valine (V).
5 . The method of claim 1 , wherein the mutation at codon 69 encodes arginine (R).
6 . The method of claim 1 , wherein the mutation at codon 74 encodes lysine (K) or serine (S).
7 . The method of claim 1 , wherein the mutation at codon 83 encodes aspartic acid (D).
8 .- 32 . (canceled)
33 . A method for determining whether an HIV-1 is resistant to a PI, comprising detecting whether a mutation in at least one of codon 418 or 482 is present in a gene encoding gag of the HIV-1, wherein the presence of the mutation correlates with resistance to a PI, thereby determining whether the HIV-1 is resistant to the PI.
34 . The method of claim 33 , further comprising detecting whether a mutation in at least one of codon 431, 437, 449, or 453 is present in a gene encoding gag of the HIV-1 in combination with the mutation in at least one of codon 418 or 482, wherein the presence of the mutations correlates with resistance to a PI, thereby determining whether the HIV-1 is resistant to the PI.
35 . The method of claim 33 , wherein the mutation at codon 418 encodes glutamic acid (E) or arginine (R).
36 . The method of claim 33 wherein the mutation at codon 482 encodes glycine (G).
37 .- 40 . (canceled)
41 . The method of claim 1 , wherein the PI is amprenavir (AMP), indinavir (IDV), nelfinavir (NFV), ritonavir (RTV), saquinavir (SQV), lopinavir (LPV) or atazanavir (ATV).
42 . The method of claim 41 , wherein the PI is AMP.
43 . The method of claim 41 , wherein the PI is IDV.
44 . The method of claim 41 , wherein the PI is NFV.
45 . The method of claim 41 , wherein the PI is RTV.
46 . The method of claim 41 , wherein the PI is SQV.
47 . The method of claim 41 , wherein the PI is LPV.
48 . The method of claim 41 , wherein the PI is ATV.