Method for determining human immunodeficiciency virus type 1 (HIV-1) hypersusceptibility to the protease inhibitor amprenavir
View Patent ↗The present invention provides an approach for developing an algorithm for determining the effectiveness of anti-viral drugs based on a comprehensive analysis of paired phenotypic and genotypic data guided by phenotypic clinical cut-offs. In one aspect, the algorithm allows one to provide a patient with effective treatment. It helps predict whether an infected individual will respond to treatment with an anti-viral compound, thereby allowing an effective treatment regimen to be designed without subjecting the patient to unnecessary side effects. Also, by avoiding the administration of ineffective drugs, considerable time and money is saved.
1. A method for determining whether an HIV-1 has an increased likelihood of being hypersusceptible to treatment with amprenavir, comprising detecting whether the protease encoded by said HIV exhibits the presence or absence of a mutation associated with hypersusceptibility to treatment with amprenavir at an amino acid position corresponding to position 39, 65, 69, or 89 of SEQ ID NO.: 1, wherein the mutation at the amino acid position corresponding to position 39 of SEQ ID NO.: 1 is S, the mutation at the amino acid position corresponding to position 65 of SEQ ID NO.: 1 is D, the mutation at the amino acid position corresponding to position 69 of SEQ ID NO.: 1 is K, and the mutation at the amino acid position corresponding to position 89 of SEQ ID NO.: 1 is M, and wherein the presence of said mutation indicates that the HIV has an increased likelihood of being hypersusceptible to treatment with amprenavir.
2. The method of claim 1 , wherein the protease has a sequence that is greater than 80% identical to SEQ ID NO:1.
3. A method for determining whether an individual infected with HIV-1 has an increased likelihood of being hypersusceptible to treatment with amprenavir, comprising detecting, in a sample from said individual, the presence or absence of a mutation associated with hypersusceptibility to treatment with amprenavir at an amino acid position corresponding to position 39, 65, 69, or 89 of SEQ ID NO.: 1, wherein the mutation at the amino acid position corresponding to position 39 of SEQ ID NO.: 1 is S, the mutation at the amino acid position corresponding to position 65 of SEQ ID NO.: 1 is D, the mutation at the amino acid position corresponding to position 69 of SEQ ID NO.: 1 is K, and the mutation at the amino acid position corresponding to position 89 of SEQ ID NO.: 1 is M, and wherein the presence of said mutation indicates that the individual has an increased likelihood of being hypersusceptible to treatment with amprenavir.
4. The method of claim 3 , wherein the protease has a sequence that is greater than 80% identical to SEQ ID NO:1.
5. The method of claim 3 , wherein the individual is undergoing or has undergone prior treatment with an anti-viral drug.
6. The method of claim 1 , wherein the method comprises detecting the presence or absence of a mutation associated with hypersusceptibility to treatment with said protease inhibitor at at least 2, 3, or 4 of the amino acid positions.