Research and Education Hospital, PCR Laboratory, Kocaeli University, Kocaeli, Turkey.
DESAM Research Institute, Near East University, Nicosia, Northern Cyprus.
Curr HIV Res. 2022 Aug 12;20(2):184-192. doi: 10.2174/1570162X20666220303104509.
Integrase strand transfer inhibitors (INSTIs) are currently the standard of practice for first-line HIV therapy for most patients. We evaluated the mutations associated with INSTI resistance in naive HIV-1 infected patients and treated them with antiretrovirals (ART).
The study, conducted in the 2018 - 2020 period, included 50 ART-naïve patients, 69 INSTI free ART-experienced patients, and 82 INSTI-experienced patients. INSTI resistance mutations were interpreted using the Stanford University HIVdb Program algorithm.
INSTI resistance was not detected in ART naïve patients. At least one INSTI resistance mutation was detected in 10% of the INSTI-free patients and 29% of the INSTI-treated patients. Major INSTI-mutations E138K, Y143R, S147G, Q148R, N155H, and E157Q were found in raltegravir. Additional mutations, E92Q, E138K, G140A, S147G, and Q148R were found in elvitegravir; E192Q, E138K/T, G140A/S, S147G, Q148H/R, N155H, E157Q were found in dolutegravir (DTG) experienced patients. According to all drug classes, drug resistance mutation prevalences were determined at the rate of 60%, 46%, and 46% in the RAL, EVG, and DTG groups, respectively.
Our findings provide data for treatment and resistance management of INSTIs and may provide feedback for INSTIs resistance surveillance consensus-building efforts. In viral rebound under INSTI treatment, INSTI-resistant mutations follow typical INSTI resistance pathways and high resistance rates. INSTI resistance genotypic analysis should be considered before any DTG-based regimes can be initiated in the future, and reduced DTG susceptibility should be carefully monitored and investigated.
整合酶链转移抑制剂（INSTIs）目前是大多数患者一线 HIV 治疗的标准方案。我们评估了初治 HIV-1 感染患者中与 INSTI 耐药相关的突变，并对其进行了抗逆转录病毒治疗（ART）。
本研究于 2018 年至 2020 年进行，共纳入 50 例初治的 ART 患者、69 例未使用 INSTI 的 ART 经验丰富的患者和 82 例使用过 INSTI 的患者。使用斯坦福大学 HIVdb 程序算法解释 INSTI 耐药突变。
在初治患者中未检测到 INSTI 耐药。在未使用 INSTI 的患者中，有 10%至少存在 1 种 INSTI 耐药突变，在使用过 INSTI 的患者中，有 29%存在至少 1 种 INSTI 耐药突变。在拉替拉韦中发现了主要的 INSTI 突变 E138K、Y143R、S147G、Q148R、N155H 和 E157Q。在埃替格韦中还发现了额外的突变 E92Q、E138K、G140A、S147G 和 Q148R；在多替拉韦（DTG）经验丰富的患者中还发现了 E192Q、E138K/T、G140A/S、S147G、Q148H/R、N155H 和 E157Q。根据所有药物类别，RAL、EVG 和 DTG 组的耐药突变流行率分别为 60%、46%和 46%。
我们的研究结果为 INSTI 的治疗和耐药管理提供了数据，并可能为 INSTI 耐药监测共识制定工作提供反馈。在 INSTI 治疗中出现病毒反弹时，INSTI 耐药突变遵循典型的 INSTI 耐药途径，耐药率较高。在未来启动任何基于 DTG 的方案之前，应考虑进行 INSTI 耐药基因型分析，并应仔细监测和研究 DTG 敏感性降低的情况。
