Shaoxing Center for Disease Control and Prevention, Shaoxing, People's Republic of China.
State Key Laboratory of Infectious Disease Prevention and Control (SKLID), National Center for AIDS/STD Control and Prevention (NCAIDS), Chinese Center for Disease Control and Prevention, (China CDC), Beijing, People's Republic of China.
Virol J. 2024 Aug 26;21(1):199. doi: 10.1186/s12985-024-02455-2.
The number and proportion of HIV/AIDS patients among older people are continuously and rapidly increasing in China. We conducted a detailed molecular epidemiological analysis of HIV-1 epidemic strains in a developed city in eastern China and found that elderly people play a crucial role in the transmission of subtypes and high pretreatment drug resistance (PDR).
A total of 1048 samples were obtained from 1129 (92.8%) newly confirmed HIV-1-positive and treatment-naive patients between 2019 and 2023. The 1316 bp target fragment of the pol gene was amplified by reverse transcription polymerase chain reaction (RT‒PCR) and nested PCR, and Maximum-likelihood (ML) phylogenetic trees and molecular transmission network were constructed to analyse the subtypes and transmission clusters. Molecular transmission network was visualized using Cytoscape with the distance threshold of 0.0075. PDR-associated mutations were determined according to the Stanford University HIV Drug Resistance Database.
A total of 933 pol sequences (89.0%, 933/1048) were successfully obtained, and twelve HIV-1 subtypes were detected. CRF07_BC was the predominant subtype, accounting for 48.1% (449/933) of sequences, followed by CRF01_AE (29.4%, 274/933). A total of 398 individuals (42.7%, 398/933) formed 89 clusters in the network. Multivariable logistic regression analysis revealed that age, nationality, subtype, and PDR were the most significant factors associated with clustering in the transmission network. The prevalence of PDR was 14.6% (136/933).PDR associated with non-nucleoside reverse transcriptase inhibitors (10.0%, 93/933) was much more common than that associated with nucleoside reverse transcriptase inhibitors (1.8%, 17/933) and protease inhibitors (3.2%, 30/933) (χ = 77.961, p < 0.001). The most frequent NNRTI mutations were K103N/S/KN/NS (52.2%, 71/136), which led to the highest proportion of high-level resistance to nevirapine and efavirenz (52.2%).
Our study revealed the important influence of elderly people on CRF07_BC transmission and the high prevalence of PDR. The clustering of drug-resistant cases was significant, which suggested the potential for localized widespread transmission of drug-resistant strains. HIV screening and the determination of PDR are recommended for older patients to improve early detection and reduce treatment failure and second-generation transmission.
中国老年人中 HIV/AIDS 患者的数量和比例正在持续快速增长。我们对中国东部一个发达城市的 HIV-1 流行株进行了详细的分子流行病学分析，发现老年人在亚群和高预处理药物耐药（PDR）的传播中起着至关重要的作用。
共收集了 2019 年至 2023 年间 1129 例（92.8%）新确诊的 HIV-1 阳性且未经治疗的患者的 1048 份样本。通过逆转录聚合酶链反应（RT-PCR）和巢式 PCR 扩增 pol 基因的 1316 bp 靶片段，构建最大似然（ML）系统发育树和分子传播网络，分析亚群和传播簇。使用 Cytoscape 可视化分子传播网络，距离阈值为 0.0075。根据斯坦福大学 HIV 耐药性数据库确定与 PDR 相关的突变。
共成功获得 933 个 pol 序列（89.0%，933/1048），检测到 12 种 HIV-1 亚型。CRF07_BC 是主要的亚型，占 48.1%（449/933），其次是 CRF01_AE（29.4%，274/933）。网络中共形成 398 个个体（42.7%，398/933）89 个簇。多变量逻辑回归分析显示，年龄、国籍、亚型和 PDR 是与网络中聚类最显著相关的因素。PDR 的流行率为 14.6%（136/933）。与核苷逆转录酶抑制剂（1.8%，17/933）和蛋白酶抑制剂（3.2%，30/933）相比，非核苷逆转录酶抑制剂（NNRTI）相关的 PDR（10.0%，93/933）更为常见（χ²=77.961，p<0.001）。最常见的 NNRTI 突变是 K103N/S/KN/NS（52.2%，71/136），导致对奈韦拉平（nevirapine）和依非韦伦（efavirenz）的高水平耐药比例最高（52.2%）。
我们的研究揭示了老年人对 CRF07_BC 传播的重要影响和高 PDR 流行率。耐药病例的聚类现象显著，这表明耐药株可能在局部广泛传播。建议对老年患者进行 HIV 筛查和 PDR 检测，以提高早期检测率，减少治疗失败和第二代传播。
