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抗逆转录病毒治疗病毒学失败患者的耐药危险因素及HIV-1传播潜在风险:中国四川的一项基于人群的研究

Risk Factors of Drug Resistance and the Potential Risk of HIV-1 Transmission of Patients with ART Virological Failure: A Population-Based Study in Sichuan, China.

作者信息

Zhou Chang, Kang Rui, Liang Shu, Fei Teng, Li Yiping, Su Ling, Li Ling, Ye Li, Zhang Yan, Yuan Dan

机构信息

Center for AIDS/STD Control and Prevention, Sichuan Center for Disease Control and Prevention, Chengdu, People's Republic of China.

School of Resource and Environmental Sciences, Wuhan University, Wuhan, People's Republic of China.

出版信息

Infect Drug Resist. 2021 Dec 7;14:5219-5233. doi: 10.2147/IDR.S334598. eCollection 2021.

Abstract

BACKGROUND

Sichuan Province, in the interior of Southwest China, is the most severe HIV-affected area in China. Few data are currently available for people living with HIV/AIDS (PLWH) with virological failure of antiretroviral therapy (ART). Estimating the HIV-1 drug-resistant spread influencing factors and transmission patterns of the HIV-1 epidemic of PLWH with ART virological failure are critical in Sichuan.

METHODS

We evaluated the drug-resistant transmission patterns on 5790 PLWH in 2018 with identified pol sequences of the five main HIV-1 subtypes (ie, subtype B, CRF08_BC, CRF85_BC, CRF07_BC, and CRF01_AE) in Sichuan Province, China. The multivariate logistic regression model was used to explore potential influencing factors of the spread of drug resistance (DR) clustering in the genetic transmission network. Spatial analyses were applied to demonstrate drug-resistant spatial clustering patterns of spatial connections of HIV-1 intercity transmission. Genetic transmission networks were performed by comparing sequences, calculating the pairwise distance, and visualizing the network.

RESULTS

There were identified 452 transmission clusters containing 2159 of 5790 patients (37.29%) in the HIV-1 genetic transmission networks. Some clinical and demographic factors (eg, route of transmission, subtype) determined the DR clustering in the genetic transmission networks. The high drug-resistant clustering rates were mainly distributed in the Southern and Northeast of Sichuan Province (eg, Deyang, Neijiang), especially for CRF85_BC, which showed the highest clustering rate. Some cities had with strong intracity links (eg, Yibin, Neijiang), some cities had with strong transmission links with another city (eg, Ziyang and Guangyuan), 12 of 37 drug resistance mutation sites had a significant difference in the five subtypes (P < 0.001).

CONCLUSION

Our findings revealed the HIV-1 drug-resistant spread influencing factors and transmission patterns of PLWH with ART virological failure, which showed regions with high drug-resistant transmission of PLWH may not be a match for regions with severe epidemics in Sichuan, and it provided evidence-based to drug-resistant transmission targeting interventions.

摘要

背景

四川省位于中国西南部内陆,是中国受艾滋病影响最严重的地区。目前关于接受抗逆转录病毒治疗(ART)出现病毒学失败的艾滋病毒/艾滋病患者(PLWH)的数据很少。在四川,估计影响艾滋病毒-1耐药性传播的因素以及接受ART病毒学失败的PLWH中艾滋病毒-1流行的传播模式至关重要。

方法

我们评估了2018年中国四川省5790例PLWH的耐药性传播模式,这些患者具有已鉴定的五种主要艾滋病毒-1亚型(即B亚型、CRF08_BC、CRF85_BC、CRF07_BC和CRF01_AE)的pol序列。采用多因素逻辑回归模型探讨基因传播网络中耐药性(DR)聚集传播的潜在影响因素。应用空间分析来展示艾滋病毒-1城市间传播空间联系的耐药性空间聚集模式。通过比较序列、计算成对距离并可视化网络来构建基因传播网络。

结果

在艾滋病毒-1基因传播网络中,共识别出452个传播簇,包含5790例患者中的2159例(37.29%)。一些临床和人口统计学因素(如传播途径、亚型)决定了基因传播网络中的DR聚集。高耐药聚集率主要分布在四川省南部和东北部(如德阳、内江),尤其是CRF85_BC,其聚集率最高。一些城市内部联系紧密(如宜宾、内江),一些城市与另一个城市有很强的传播联系(如资阳和广元),37个耐药突变位点中的12个在五种亚型中有显著差异(P<0.001)。

结论

我们的研究结果揭示了接受ART病毒学失败的PLWH中艾滋病毒-1耐药性传播的影响因素和传播模式,表明PLWH耐药性高传播地区可能与四川严重流行地区不匹配,并为耐药性传播靶向干预提供了循证依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff66/8666109/3255616a747c/IDR-14-5219-g0001.jpg

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