Fan Weiguang, Wang Xiaodong, Zhang Yuchen, Meng Juan, Su Miaomiao, Yang Xuegang, Shi Haoxi, Shi Penghui, Lu Xinli
Clinical Laboratory, The People's Hospital of Baoding, Baoding, Hebei, China.
Infection Division, The People's Hospital of Baoding, Baoding, Hebei, China.
Front Genet. 2022 Sep 14;13:975397. doi: 10.3389/fgene.2022.975397. eCollection 2022.
Antiretroviral therapy (ART) regimens containing integrase strand transfer inhibitors (INSTIs) are the recommended treatment for human immunodeficiency virus type 1 (HIV-1)-infected patients in the most recent guidelines in China. In this study, we investigated INSTI resistance mutations in newly diagnosed therapy-naive HIV-positive patients in Baoding City, Hebei Province (China) to provide guidance for implementing routine INSTI-associated HIV-1 genotypic resistance testing. Plasma samples were collected from HIV-1-infected patients without treatment at Baoding People's Hospital from January 2020 to December 2021. The part of HIV-1 gene encoding integrase was amplified, sequenced, and analyzed for INSTI resistance. Clinical data including demographic data, CD4 T cell counts, HIV-RNA loads, and resistance mutations were collected. Treatment-naïve HIV-1 patients ( = 131) were enrolled. We identified ten genotypes, and the predominant genotype was CRF01_AE in 67 patients (51.15%), CRF07_ BC in 39 patients (29.77%), subtype B in 11 patients (8.40%), and other subtypes (CRF68_01B, 3.82%; CRF55_01B, 1.53%, CRF80_0107, 1.53%; URFs 1.53%; and CRF103_01B, CRF59_01B, and CRF65_cpx, 1.4% each). Four major (E138A, R263k, G140S, and S147G) and three accessory (H51Y, Q146QL, and S153F) INSTI-resistance mutations were observed (genotype CRF01_AE, three patients; genotype B, one patient; and genotype CRF07_BC, one patient), resulting in different degrees of resistance to the following five INSTIs: raltegravir, elvitegravir, dolutegravir, bictegravir, and cabotegravir. The overall resistance rate was 3.82% (5/131). All INSTI-resistant strains were cross-resistant. The primary INSTI drug resistance rate among newly diagnosed HIV-infected patients in Baoding was low, but monitoring and research on HIV INSTI resistance should be strengthened in Baoding because INSTI-based regimen prescriptions are anticipated to increase in the near future.
在中国最新的指南中，含有整合酶链转移抑制剂（INSTIs）的抗逆转录病毒疗法（ART）方案是推荐用于治疗1型人类免疫缺陷病毒（HIV-1）感染患者的疗法。在本研究中，我们调查了中国河北省保定市新诊断的未接受过治疗的HIV阳性患者中的INSTI耐药突变情况，以便为实施常规的与INSTI相关的HIV-1基因型耐药性检测提供指导。于2020年1月至2021年12月期间从保定市人民医院未接受治疗的HIV-1感染患者中采集血浆样本。对HIV-1基因编码整合酶的部分进行扩增、测序并分析INSTI耐药情况。收集包括人口统计学数据、CD4 T细胞计数、HIV-RNA载量和耐药突变在内的临床资料。纳入了131例未接受过治疗的HIV-1患者。我们鉴定出了10种基因型，其中主要基因型为CRF01_AE，共67例患者（51.15%）；CRF07_BC，共39例患者（29.77%）；B亚型，共11例患者（8.40%）；以及其他亚型（CRF68_01B，3.82%；CRF55_01B，1.53%；CRF80_0107，1.53%；未定型重组形式，1.53%；CRF103_01B、CRF59_01B和CRF65_cpx，各1.4%）。观察到了4种主要的（E138A、R263k、G140S和S147G）和3种次要的（H51Y、Q146QL和S153F）INSTI耐药突变（CRF01_AE基因型，3例患者；B基因型，1例患者；CRF07_BC基因型，1例患者），导致对以下5种INSTIs产生不同程度的耐药：拉替拉韦、埃替拉韦、多替拉韦、比克替拉韦和卡博特韦。总体耐药率为3.82%（5/131）。所有INSTI耐药菌株均存在交叉耐药。保定市新诊断的HIV感染患者中主要的INSTI耐药率较低，但鉴于预计在不久的将来基于INSTI的方案处方会增加，因此在保定市应加强对HIV INSTI耐药性的监测和研究。
