Dynamics of Raltegravir Resistance Profile in an HIV Type 2-Infected Patient
Dynamics of Raltegravir Resistance Profile in an HIV Type 2-Infected Patient
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DOI：
10.1089/aid.2009.0039
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发表时间：
2009-08-01
影响因子：
1.5
通讯作者：
Smit, Erasmus
中科院分区：
文献类型：
--
作者：
Xu, Li;Anderson, Jane;Smit, Erasmus
通过群体和克隆序列分析，从基线、治疗期间和停止治疗后分析HIV-2病毒对氯丙氨酸的耐药性的进化动态。在所研究的HIV-2患者中，RAR方案的治疗失败与通过N155H耐药途径出现突变以及随后切换到Y143C突变途径有关。这项研究还发现了四个新的继发性突变，Q91R、S147G、A153G和M183I，这些突变以前在失败的HIV-1患者中没有报道。涉及Y143C通路的耐药变异在停止Ral治疗后持续了4周以上。所有与耐药相关的突变在停止Ral治疗20周后均消失。我们的发现提供了证据支持这样的假设，即如HIV-1所示，在HIV-2中很可能存在链转移IN-IS之间的实质性交叉耐药。
The evolutionary dynamics of RAL resistance in the HIV-2 virus were examined through population and clonal sequence analysis of the IN from baseline, during treatment, and after stopping RAL therapy. The treatment failure of an RAL regimen in the HIV-2 patient studied was associated with the emergence of mutations via the N155H resistance pathway and subsequent switching to the Y143C mutational route. This study has also identified four novel secondary mutations, Q91R, S147G, A153G, and M183I, not previously reported in HIV-1 patients failing RAL therapy. Resistant variants involving the Y143C pathway were noted to have persisted beyond 4 weeks following the cessation of RAL therapy. All resistance-associated mutations were lost at 20 weeks after stopping RAL therapy. Our findings provide evidence supporting the supposition that substantial cross-resistance between strand transfer IN-Is is likely in HIV-2 as shown in HIV-1.