Factors associated with HIV-1 resistance to integrase strand transfer inhibitors in Spain: Implications for dolutegravir-containing regimens.
Factors associated with HIV-1 resistance to integrase strand transfer inhibitors in Spain: Implications for dolutegravir-containing regimens.
复制标题
与西班牙抗HIV-1抗性的HIV-1抗性相关的因素：对含Dolutegravir的方案的影响。
DOI：
10.3389/fmicb.2022.1051096
复制
发表时间：
2022
影响因子：
5.2
通讯作者：
Thomson, Michael M.
中科院分区：
文献类型：
--
作者：
Gil, Horacio;Delgado, Elena;Benito, Sonia;Moreno-Lorenzo, Maria;Thomson, Michael M.
在感染人类免疫缺陷病毒1型（HIV - 1）的患者中，含整合酶链转移抑制剂（INSTI）的治疗方案在全球范围内有所增加。最近，世界卫生组织强调需要加快向基于多替拉韦（DTG）的抗逆转录病毒（ARV）治疗的转变。然而，建议持续监测INSTI耐药性。在这项研究中，分析了在西班牙诊断出的与INSTI耐药性相关的临床、流行病学和病毒学特征。使用桑格群体测序法对2008年至2021年间从HIV - 1感染患者收集的样本在整合酶、蛋白酶和逆转录酶方面进行了分析。使用斯坦福大学HIVdb程序评估抗逆转录病毒药物耐药性。在2696名患者中，174名（6.5%）对INSTI有耐药性，且均对第一代INSTI耐药，71名（2.6%）对第二代INSTI也有耐药性。其中，只有5人仅使用过DTG这一种INSTI，在这些人中，耐药性的产生与治疗依从性差和/或对其他抗逆转录病毒药物类别耐药有关。在新诊断的HIV - 1感染者中，0.92%携带对INSTI耐药的病毒，其患病率长期保持在较低水平，且只有1人对DTG有低水平耐药。注射吸毒者、年龄超过39岁、对其他抗逆转录病毒药物类别耐药以及从确诊到现在时间较长都与INSTI耐药性相关（p < 0.001）。非B亚型对INSTI耐药的病毒缺乏Q148H + G140S耐药途径，且比B亚型病毒显示出更低的INSTI耐药水平。总之，INSTI耐药并不常见，与长期感染、年龄较大以及对其他抗逆转录病毒药物类别额外耐药相关，在新诊断的HIV - 1感染中很少见。我们的研究结果也支持在一线治疗中优先使用含DTG的治疗方案，尽管鼓励对INSTI耐药性进行监测。
Integrase strand transfer inhibitor (INSTI)-containing regimens in HIV-1-infected patients have experienced a global increase. Recently, WHO has emphasized the need to fast-track the transition to dolutegravir (DTG)-based antiretroviral (ARV) treatments. However, continued surveillance of INSTI resistance is recommended. In this study, clinical, epidemiological, and virological features associated with INSTI resistance diagnosed in Spain were analyzed. Samples collected between 2008 and 2021 from HIV-1-infected patients were analyzed in integrase, protease, and reverse transcriptase using Sanger population sequencing. ARV drug resistance was evaluated with the Stanford University HIVdb program. Among 2,696 patients, 174 (6.5%) had INSTI resistance, all of them to first-generation INSTIs, and 71 (2.6%) had also resistance to second-generation INSTIs. Of these, only 5 individuals were exposed to DTG as the only INSTI, in whom resistance development was associated with poor treatment adherence and/or resistance to other ARV classes. Of newly HIV-1-diagnosed individuals, 0.92% harbored INSTI-resistant viruses, with low prevalences maintained along time, and only one had low-level resistance to DTG. Persons who inject drugs, age over 39 years, resistance to other ARV classes, and longer time from diagnosis were associated with INSTI resistance (p < 0.001). Non-subtype B INSTI-resistant viruses lacked the Q148H + G140S resistance pathway and showed lower INSTI resistance levels than subtype B viruses. In conclusion, INSTI resistance is uncommon and associated with long-term infections, older age and additional resistance to other ARV drug classes, and is rare in newly diagnosed HIV-1 infections. Our results also support the preferential use of DTG-containing regimens in first-line treatments, although surveillance of INSTI resistance is encouraged.
登录
查看更多内容
影响因子：
5.2
作者：
Fourati, Slim;Charpentier, Charlotte;Marcelin, Anne-Genevieve
通讯作者：
Marcelin, Anne-Genevieve
影响因子：
5.2
作者：
Castagna, Antonella;Ferrara, Micol;Lazzarin, Adriano
通讯作者：
Lazzarin, Adriano
影响因子：
168.9
作者：
Lennox, Jeffrey L.;Dejesus, Edwin;Sklar, Peter
通讯作者：
Sklar, Peter
影响因子：
3.8
作者：
Liu, Lifeng;Dai, Lili;Zhang, Tong
通讯作者：
Zhang, Tong
影响因子：
5.2
作者：
Alvarez, Marta;Casas, Paz;Palau Concejo, Paula
通讯作者：
Palau Concejo, Paula