HIV integrase variability and genetic barrier in antiretroviral naive and experienced patients
HIV integrase variability and genetic barrier in antiretroviral naive and experienced patients
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DOI：
10.1186/1743-422x-8-149
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发表时间：
2011-03-31
期刊：
影响因子：
4.8
通讯作者：
Baldanti, Fausto
中科院分区：
文献类型：
--
作者：
Piralla, Antonio;Paolucci, Stefania;Baldanti, Fausto
背景：HIV-1整合酶（IN）在不同HIV-1亚型初治患者中的变异性是一个主要问题。事实上，既往暴露于除IN抑制剂（INI）以外的抗逆转录病毒药物对IN变异性的影响尚未得到令人满意的定义。此外，特定INI耐药突变的遗传障碍仍有待calculated.Methods：IN变异性进行了分析，并与逆转录酶（RT）和蛋白酶（PR）的变异性进行了比较，在41个治疗幼稚和54 RT抑制剂（RTI）和蛋白酶抑制剂（PRI）经验丰富的患者感染亚型B和非B菌株。此外，还平行分析了4种HIV-2毒株。频率和分布的IN突变HAART天真和RTI/PI经验丰富的患者之间进行了比较; 27个氨基酸的位置相关的INI易感性的遗传屏障calculatedas well.Results：原发性突变与耐药性INI未检测到在以前没有治疗过这类药物的患者。然而，一些已被证明有助于INI耐药的继发突变被发现。只有有限的差异，在患者群体之间的密码子使用分布被发现。HIV-2株从INI初治患者表现出既存在原发性和继发性resistance mutations.Conclusion：暴露于抗病毒药物以外的INI似乎并没有显着影响的出现与INI耐药有关的突变。HIV-2株对INI的敏感性可能降低。
Background: HIV-1 integrase (IN) variability in treatment naive patients with different HIV-1 subtypes is a major issue. In fact, the effect of previous exposure to antiretrovirals other than IN inhibitors (INI) on IN variability has not been satisfactorily defined. In addition, the genetic barrier for specific INI resistance mutations remains to be calculated.Methods: IN variability was analyzed and compared with reverse transcriptase (RT) and protease (PR) variability in 41 treatment naive and 54 RT inhibitor (RTI) and protease inhibitor (PRI) experienced patients from subjects infected with subtype B and non-B strains. In addition, four HIV-2 strains were analyzed in parallel. Frequency and distribution of IN mutations were compared between HAART naive and RTI/PI experienced patients; the genetic barrier for 27 amino acid positions related to INI susceptibility was calculated as well.Results: Primary mutations associated with resistance to INI were not detected in patients not previously treated with this class of drug. However, some secondary mutations which have been shown to contribute to INI resistance were found. Only limited differences in codon usage distribution between patient groups were found. HIV-2 strains from INI naive patients showed the presence of both primary and secondary resistance mutations.Conclusion: Exposure to antivirals other than INI does not seem to significantly influence the emergence of mutations implicated in INI resistance. HIV-2 strain might have reduced susceptibility to INI.