Department of Global Health, Academic Medical Center of the University of Amsterdam, and Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands.
Joep Lange Institute, Department of Global Health, Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands.
J Antimicrob Chemother. 2018 May 1;73(5):1167-1172. doi: 10.1093/jac/dky005.
To investigate the prevalence and patterns of major and accessory resistance mutations associated with integrase strand transfer inhibitors (INSTIs), across diverse HIV-1 subtypes in sub-Saharan Africa.
pol gene sequences were obtained using Illumina next-generation sequencing from 425 INSTI-naive HIV-infected adults from Kenya (21.2%), Nigeria (7.3%), South Africa (22.8%), Uganda (25.2%) and Zambia (23.5%). Drug resistance interpretation was based on the IAS 2017 mutation list and accessory mutations from Stanford HIVdb with resistance penalty scores of ≥10 to at least 1 INSTI. Resistance was further classified based on sensitivity thresholds of ≥20% (Sanger sequencing) and 1%-20% for low-frequency variants (next-generation sequencing).
Of 425 genotypes, 48.7% were subtype C, 28.5% A, 10.1% D, 2.8% G and 9.9% were recombinants. Major INSTI resistance mutations were detected only at <20% threshold, at a prevalence of 2.4% (2.5% in subtype A, 2.4% C, 0% D, 8.3% G and 2.4% in recombinants) and included T66A/I (0.7%), E92G (0.5%), Y143C/S (0.7%), S147G (0.2%) and Q148R (0.5%). Accessory mutations occurred at a prevalence of 15.1% at the ≥20% threshold (23.1% in subtype A, 8.7% C, 11.6% D, 25% G and 23.8% in recombinants), and included L74I/M (10.4%), Q95K (0.5%), T97A (4%), E157Q (0.7%) and G163R/K (0.7%).
Major INSTI resistance mutations were rare and only occurred at low-level resistance detection thresholds. INSTI-based regimens are expected to be effective across the different major HIV-1 subtypes in the region.
调查与整合酶链转移抑制剂（INSTIs）相关的主要和辅助耐药突变在撒哈拉以南非洲不同 HIV-1 亚型中的流行情况和模式。
使用 Illumina 下一代测序从肯尼亚（21.2%）、尼日利亚（7.3%）、南非（22.8%）、乌干达（25.2%）和赞比亚（23.5%）的 425 名 INSTI 初治 HIV 感染成人中获得 pol 基因序列。耐药性解释基于 IAS 2017 突变列表和斯坦福 HIVdb 的辅助突变，耐药罚分≥10 分，至少有 1 种 INSTI。耐药性进一步根据≥20%（Sanger 测序）和 1%-20%（下一代测序）低频变异的灵敏度阈值进行分类。
在 425 种基因型中，48.7%为亚型 C，28.5%为 A，10.1%为 D，2.8%为 G，9.9%为重组型。主要的 INSTI 耐药突变仅在<20%的阈值下检测到，流行率为 2.4%（A 亚型为 2.4%，C 亚型为 2.4%，D 亚型为 0%，G 亚型为 8.3%，重组型为 2.4%），包括 T66A/I（0.7%）、E92G（0.5%）、Y143C/S（0.7%）、S147G（0.2%）和 Q148R（0.5%）。辅助突变的流行率为 15.1%，在≥20%的阈值下（A 亚型为 23.1%，C 亚型为 8.7%，D 亚型为 11.6%，G 亚型为 25%，重组型为 23.8%），包括 L74I/M（10.4%）、Q95K（0.5%）、T97A（4%）、E157Q（0.7%）和 G163R/K（0.7%）。
主要的 INSTI 耐药突变罕见，仅在低水平耐药检测阈值下发生。基于 INSTI 的方案有望在该地区不同主要 HIV-1 亚型中有效。
