Methods and Compositions for Determining Virus Susceptibility to Integrase Inhibitors

摘要

Methods and compositions for the efficient and accurate determination of HIV susceptibility to an integrase inhibitor and/or HIV replication capacity are provided. In certain aspects, the methods involve detecting in a biological sample a nucleic acid encoding an HIV integrase that comprises a primary mutation at codon 143, wherein the mutation at codon 143 does not encode arginine (R) or cysteine (C), and wherein the presence of the integrase-encoding nucleic acid in the biological sample indicates that the HIV has a decreased susceptibility to an integrase inhibitor or altered replication capacity relative to a reference HIV. In certain embodiments, the HIV also contains one or more secondary mutations in integrase. Also provided are methods for determining the selective advantage of a mutation or mutation profile based on the difficulty to create the mutation, and its effect on susceptibility to an integrase inhibitor or replication capacity.

主权项

1. A method for determining the susceptibility of a human immunodeficiency virus (HIV) from a patient to an integrase inhibitor and for treating the patient, comprising:
a) detecting in a biological sample from a patient infected with HIV the presence or absence of a mutation at codon 143 of a nucleic acid encoding an HIV integrase, wherein the mutation at codon 143 encodes a glycine residue instead of a tyrosine residue (Y143G) b) determining that the patient's HIV has a decreased susceptibility to the integrase inhibitor relative to a reference HIV if the mutation in the integrase-encoding nucleic acid is present; and c) treating the patient with an effective amount of an inhibitor other than the integrase inhibitor if the patient's HIV is determined to have decreased susceptibility to the integrase inhibitor.