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    • 6. 发明申请
    • METHODS AND COMPOSITIONS FOR DETERMINING VIRUS SUSCEPTIBILITY TO INTEGRASE INHIBITORS
    • 用于确定集成抑制剂病毒易感性的方法和组合物
    • WO2012116371A1
    • 2012-08-30
    • PCT/US2012/026794
    • 2012-02-27
    • LABORATORY CORPORATION OF AMERICA HOLDINGSHUANG, WeiPETROPOULOS, Christos John
    • HUANG, WeiPETROPOULOS, Christos John
    • C12Q1/70
    • C12Q1/703C12Q2600/106C12Q2600/156
    • 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.
    • 提供了有效和准确地确定对整合酶抑制剂和/或HIV复制能力的HIV敏感性的方法和组合物。 在某些方面,所述方法包括在生物样品中检测编码HIV整合酶的核酸,所述核酸编码包含143位密码子的初级突变,其中143位密码子的突变不编码精氨酸(R)或半胱氨酸(C),其中 生物样品中整合酶编码核酸的存在表明HIV相对于参考HIV具有降低的对整合酶抑制剂的易感性或改变的复制能力。 在某些实施方案中,HIV还含有整合酶中的一个或多个次要突变。 还提供了基于产生突变的难度确定突变或突变特征的选择性优势的方法及其对整合酶抑制剂或复制能力的易感性的影响。