HIV-2 Integrase Polymorphisms and Longitudinal Genotypic Analysis of HIV-2 Infected Patients Failing a Raltegravir-Containing Regimen
HIV-2 Integrase Polymorphisms and Longitudinal Genotypic Analysis of HIV-2 Infected Patients Failing a Raltegravir-Containing Regimen
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DOI：
10.1371/journal.pone.0092747
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发表时间：
2014-03-28
期刊：
影响因子：
3.7
通讯作者：
Camacho, Ricardo Jorge
中科院分区：
文献类型：
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作者：
Cavaco-Silva, Joana;Abecasis, Ana;Camacho, Ricardo Jorge
为了研究HIV-2整合酶基因的多态性及其耐药途径，我们研究了63名未接受整合酶链转移抑制药(INSTI)治疗的HIV-2患者，以及10名接受Raltegravir补救治疗的病毒学失败患者。所有患者均感染了HIV-2 A组，整合酶残基的保守率为61.4%，包括催化基序残基。在幼稚患者的病毒群体中没有检测到INSTI主要耐药性突变，但观察到了两个氨基酸，它们是HIV-1中对INSTI的次级耐药性突变。10名服用Raltegravir的患者通过三条主要的遗传途径发生耐药突变：N155H、Q148R，最终是E92Q-T97A。首选155径路(7/10例)。在我们的HIV-2人群(V151I和D232N)中也观察到了与HIV-1中的拉替格列韦耐药相关的其他突变，以及几个以前未报道的新突变。从这项研究中检索到的数据将有助于建立一个更强大的针对HIV-2的算法，用于对Raltegravir耐药性的基因解释，并有助于改善对HIV-2感染患者的临床监测。
To characterize the HIV-2 integrase gene polymorphisms and the pathways to resistance of HIV-2 patients failing a raltegravir-containing regimen, we studied 63 integrase strand transfer inhibitors (INSTI)-naive patients, and 10 heavily pretreated patients exhibiting virological failure while receiving a salvage raltegravir-containing regimen. All patients were infected by HIV-2 group A. 61.4% of the integrase residues were conserved, including the catalytic motif residues. No INSTI-major resistance mutations were detected in the virus population from naive patients, but two amino acids that are secondary resistance mutations to INSTIs in HIV-1 were observed. The 10 raltegravir-experienced patients exhibited resistance mutations via three main genetic pathways: N155H, Q148R, and eventually E92Q - T97A. The 155 pathway was preferentially used (7/10 patients). Other mutations associated to raltegravir resistance in HIV-1 were also observed in our HIV-2 population (V151I and D232N), along with several novel mutations previously unreported. Data retrieved from this study should help build a more robust HIV-2-specific algorithm for the genotypic interpretation of raltegravir resistance, and contribute to improve the clinical monitoring of HIV-2-infected patients.