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台湾南部地区HIV-1整合酶链转移抑制剂耐药情况

HIV-1 integrase strand-transfer inhibitor resistance in southern Taiwan.

作者信息

Tsai Hung-Chin, Chen I-Tzu, Wu Kuan-Sheng, Tseng Yu-Ting, Sy Cheng-Len, Chen Jui-Kuang, Lee Shin-Jung Susan, Chen Yao-Shen

机构信息

Division of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

出版信息

Oncotarget. 2018 May 18;9(38):24927-24935. doi: 10.18632/oncotarget.24837.

Abstract

The use of antiretroviral therapy has reduced rates of mortality and morbidity in patients with human immunodeficiency virus/acquired immune deficiency syndrome(HIV/AIDS). However, transmission of drug-resistant strains poses a challenge to control the spread of HIV-1. Primary resistance to integrase strand-transfer inhibitors (INSTIs) is rare despite their increased use. The prevalence of transmitted drug resistance (TDR) to INSTIs was 0.9% in northern Taiwan. This study was to analyse the prevalence and risk factors of TDR to INSTIs in southern Taiwan. In this study, we enrolled antiretroviral treatment-naïve HIV-1-infected subjects who underwent voluntary counselling and testing from 2013 to 2016 in southern Taiwan. Genotypic drug resistance, coreceptor tropism (CRT) and INSTI resistance were determined. Logistic regression was used to analyse the risk factors for INSTI polymorphic substitution. Sequences were obtained from 184 consecutive individuals, of whom 96.7% were men who have sex with men and 3.3% were heterosexual. Of the patients, 10% (19/183) had hepatitis B and 33.3% (61/183) had syphilis infection. Subtype B HIV-1 strains were found in 96.1% of the patients. Fifteen patients (8.4%, 15/178) harboured nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors or protease inhibitors resistance. CCR-5 coreceptors were used by 71.4% (130/184) of the patients. None of the patients had INSTI resistance-associated mutations, however 16 patients had INSTI polymorphic substitutions, and they were associated with a higher HIV viral load ( = 0.03, OR 2.4, CI 1.1-5.3) and syphilis infection ( = 0.03, OR 3.7, CI 1.1-12.0). In conclusion, no signature INSTI resistance-associated mutations were detected in our cohort. Continued monitoring of TDR to INSTI is needed due to the increased use of INSTIs.

摘要

抗逆转录病毒疗法的使用降低了人类免疫缺陷病毒/获得性免疫缺陷综合征(HIV/AIDS)患者的死亡率和发病率。然而,耐药菌株的传播对控制HIV-1的传播构成了挑战。尽管整合酶链转移抑制剂(INSTIs)的使用增加,但其原发性耐药却很少见。在台湾北部,对INSTIs的传播性耐药(TDR)患病率为0.9%。本研究旨在分析台湾南部对INSTIs的TDR患病率及危险因素。在本研究中,我们纳入了2013年至2016年在台湾南部接受自愿咨询和检测的未接受过抗逆转录病毒治疗的HIV-1感染受试者。测定了基因型耐药性、共受体嗜性(CRT)和INSTI耐药性。采用逻辑回归分析INSTI多态性替代的危险因素。从184名连续个体中获得序列,其中96.7%为男男性行为者,3.3%为异性恋者。患者中,10%(19/183)患有乙型肝炎,33.3%(61/183)患有梅毒感染。96.1%的患者中发现B型HIV-1毒株。15名患者(8.4%,15/178)携带核苷类逆转录酶抑制剂、非核苷类逆转录酶抑制剂或蛋白酶抑制剂耐药。71.4%(130/184)的患者使用CCR-5共受体。患者均无INSTI耐药相关突变,但有16名患者存在INSTI多态性替代,且与较高的HIV病毒载量(P = 0.03,OR 2.4,CI 1.1 - 5.3)和梅毒感染(P = 0.03,OR 3.7,CI 1.1 -

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fba/5982757/5fe144357b8a/oncotarget-09-24927-g001.jpg

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