Department of Infectious, Tropical Diseases and Immune Deficiency, Pomeranian Medical University in Szczecin, 71455 Szczecin, Poland.
Outpatient Clinic for AIDS Diagnostics and Therapy, Specialistic Hospital in Chorzow, 41500 Chorzow, Poland.
Viruses. 2024 Oct 11;16(10):1597. doi: 10.3390/v16101597.
With the widespread use of integrase inhibitors and the expanding use of long-acting cabotegravir in both pre-exposure prophylaxis and antiretroviral treatment, molecular surveillance on the transmission of integrase resistance has regained clinical significance. This study aimed to determine the frequency of INSTI-transmitted drug resistance mutations (DRMs) among treatment-naïve individuals in Poland from 2016 to 2023. INSTI resistance was analyzed in 882 antiretroviral treatment-naïve individuals using Sanger sequencing. Integrase DRMs were defined based on the Stanford HIV drug resistance database scores. Phylogeny was used to investigate subtyping and clustering. For the analysis of time-trends, logistic regression was used. Major (E138K and R263K) integrase mutations were detected in 0.45% of cases with minor resistance observed in 14.85%, most commonly (13.95%) E157Q. Overall, no major clusters of transmitted drug resistance were identified, and the transmission of E157Q showed a decreasing trend ( < 0.001). While the frequency of sub-subtype A6 increased, it was predominantly found among migrants and associated with L74 mutations. The frequency of major integrase-transmitted DRMs remains low, despite the changes in subtype variability. Surveillance of changing HIV molecular variation patterns is vital from the perspective of the optimal use of integrase inhibitors, especially due to expanding long-acting cabotegravir implementation.
随着整合酶抑制剂的广泛应用和长效卡替拉韦在暴露前预防和抗逆转录病毒治疗中的应用不断扩大，整合酶耐药的分子监测再次具有临床意义。本研究旨在确定 2016 年至 2023 年期间波兰未经治疗的个体中整合酶耐药突变（INSTI-DRM）的发生率。使用 Sanger 测序法对 882 名未经抗逆转录病毒治疗的个体进行 INSTI 耐药性分析。根据斯坦福 HIV 耐药数据库评分定义整合酶耐药突变。采用系统发生学方法研究亚型和聚类。为了分析时间趋势，使用逻辑回归。主要（E138K 和 R263K）整合酶突变在 0.45%的病例中检测到，而 14.85%的病例中观察到次要耐药，最常见的是 E157Q（13.95%）。总体而言，未发现主要的耐药传播群集，E157Q 的传播呈下降趋势（<0.001）。虽然亚 A6 亚型的频率增加，但主要见于移民，与 L74 突变有关。尽管亚型变异性发生变化，但主要整合酶传播的耐药突变频率仍然较低。从整合酶抑制剂最佳使用的角度来看，监测 HIV 分子变异模式的变化至关重要，尤其是由于长效卡替拉韦的应用不断扩大。
