Zhu Min, Sun Zhou, Zhang Xingliang, Luo Wenjie, Wu Sisheng, Ye Ling, Xu Ke, Chen Junfang
Department of HIV/AIDS Control and Prevention, Hangzhou Center for Disease Control and Prevention (Hangzhou Health Supervision Institution), Hangzhou, China.
Front Microbiol. 2024 Oct 18;15:1475548. doi: 10.3389/fmicb.2024.1475548. eCollection 2024.
HIV drug resistance (HIVDR) has become a threat to the elimination of the AIDS epidemic due to the global scale-up of antiretroviral therapy (ART) for HIV-infected individuals. This study aims to investigate the epidemiological dynamics and molecular characterization of HIV pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in Hangzhou, a developed region in China.
An epidemiological survey combined with a molecular transmission network and Bayesian analysis was conducted. A total of 3,596 individuals with newly confirmed HIV infections (from 2020 to 2023) and 164 individuals with ART failure (from 2021 to 2023) were included. The molecular transmission network was used to identify key drug-resistant transmission clusters, while the Bayesian analysis was utilized to trace the origins and spread of these clusters.
The overall prevalence of PDR was found to be 8.4% (303/3596). Among these cases, PDR to non-nucleoside reverse transcriptase inhibitors (NNRTIs) accounted for 4.7% (170/3596), significantly higher than the resistance observed for protease inhibitors (PIs; 2.8%, < 0.001) and nucleoside reverse transcriptase inhibitors (NRTIs; 1.4%, < 0.001). Multivariate logistic regression analysis revealed a significantly higher PDR value among individuals infected with the CRF07_BC subtype compared to those with the CRF08_BC subtype (aOR = 0.56, 95% CI = 0.359-0.859, = 0.008). The molecular transmission network analysis identified the transmission of the drug resistance mutation (DRM) Q58E within the clusters of the CRF07_BC subtype. The Bayesian analysis suggested that these clusters were introduced into Hangzhou from Shenzhen between 2005 and 2012. Furthermore, the study highlighted 50.6% (83/164) prevalence of ADR among individuals experiencing ART failure. The combined molecular network analysis of virological failure and newly confirmed HIV infections indicated the transmission of the K103N mutation between these groups.
In conclusion, targeted interventions may be necessary for specific subtypes and transmission clusters to control the spread of drug-resistant HIV. Continuous monitoring of resistance patterns is critical to inform treatment strategies and optimize ART regimens.
由于全球范围内对感染HIV个体的抗逆转录病毒疗法（ART）的扩大应用，HIV耐药性（HIVDR）已成为消除艾滋病流行的一大威胁。本研究旨在调查中国发达地区杭州HIV治疗前耐药性（PDR）和获得性耐药性（ADR）的流行病学动态及分子特征。
开展了一项结合分子传播网络和贝叶斯分析的流行病学调查。共纳入3596例新确诊的HIV感染者（2020年至2023年）和164例ART治疗失败的个体（2021年至2023年）。分子传播网络用于识别关键的耐药传播簇，而贝叶斯分析则用于追踪这些簇的起源和传播。
发现PDR的总体患病率为8.4%（303/3596）。在这些病例中，对非核苷类逆转录酶抑制剂（NNRTIs）的PDR占4.7%（170/3596），显著高于蛋白酶抑制剂（PIs；2.8%，<0.001）和核苷类逆转录酶抑制剂（NRTIs；1.4%，<0.001）的耐药率。多因素逻辑回归分析显示，与感染CRF08_BC亚型的个体相比，感染CRF07_BC亚型的个体的PDR值显著更高（调整后比值比[aOR]=0.56，9�%置信区间[CI]=0.359 - 0.859，P = 0.008）。分子传播网络分析确定了CRF07_BC亚型簇内耐药突变（DRM）Q58E的传播。贝叶斯分析表明，这些簇在2005年至2012年期间从深圳传入杭州。此外，该研究强调在ART治疗失败的个体中ADR的患病率为50.6%（83/164）。病毒学失败和新确诊的HIV感染者的联合分子网络分析表明K103N突变在这些群体之间传播。
总之，针对特定亚型和传播簇进行有针对性的干预对于控制耐药HIV的传播可能是必要的。持续监测耐药模式对于指导治疗策略和优化ART方案至关重要。
