Methods and compositions for determining virus susceptibility to non-nucleoside reverse transcriptase inhibitors

A method for selecting a treatment for a patient having a human immunodeficiency virus (HIV) infection, comprising:

• (a) obtaining an HIV from a patient;
• (b) determining whether the HIV is susceptible to a non-nucleoside reverse transcriptase inhibitor (NNRTI), comprising:
• i) detecting the presence or absence of a mutation at codon 188 in a nucleic acid encoding reverse transcriptase of the HIV, wherein the codon number of said reverse transcriptase corresponds to the codon number in the wild type HIV isolate NL4-3 sequence and wherein the mutation at codon 188 encodes leucine (L) instead of tyrosine (Y);
• and
• ii) determining that the HIV has reduced susceptibility to the NNRTI if the mutation at codon 188 is present;
• and
• (c) treating the patient with the NNRTI if the HIV is determined to be susceptible to the NNRTI as determined in step (b) or treating the patient with a different viral inhibitor if the HIV is determined to have reduced susceptibility to the NNRTI in step (b).

A method for determining the selective advantage of a reverse transcriptase mutation or mutation profile, comprising:

• determining the number of nucleotide substitutions in a reverse transcriptase-encoding nucleic acid at codons 101, 138, 179, 181, 188, 221, 227, or 230 that are required to convert the wild type codon to a particular mutant codon encoding an amino acid substitution;
• determining the reduction in susceptibility to a reverse transcriptase inhibitor that is conferred by the amino acid substitution at codons 101, 138, 179, 181, 188, 221, 227, or 230;
• determining the impact of the amino acid substitution at codons 101, 138, 179, 181, 188, 221, 227, or 230 on replication capacity;
• determining the number of secondary mutations present in the reverse transcriptase-encoding nucleic acid and their impact on susceptibility to the reverse transcriptase inhibitor, on replication capacity, or on both susceptibility to the reverse transcriptase inhibitor and replication capacity;
• and
• determining the selective advantage for the mutation or mutation profile, wherein the fewer the number of nucleotide substitutions required for the amino acid substitution, the higher the reduction of the susceptibility to the reverse transcriptase inhibitor, the lower the impact on replication capacity, and the fewer the number of secondary mutations required to achieve the reduction in susceptibility to the reverse transcriptase inhibitor, the greater the selective advantage for the mutation or mutation profile, thereby determining the selective advantage for the mutation or mutation profile.