云南省德宏州2012-2014年成年艾滋病患者抗病毒治疗耐药发生及影响因素研究

姚仕堂; 姚媛; 时允; 李品银; 许元武; 杨文芹; 章银娣; 尹春英; 寸柳青; 翟志坚; 何纳; 段松

文章摘要

姚仕堂,姚媛,时允,李品银,许元武,杨文芹,章银娣,尹春英,寸柳青,翟志坚,何纳,段松.云南省德宏州2012-2014年成年艾滋病患者抗病毒治疗耐药发生及影响因素研究[J].中华流行病学杂志,2016,37(7):949-954

云南省德宏州2012-2014年成年艾滋病患者抗病毒治疗耐药发生及影响因素研究

Drug resistance and influencing factors in adult AIDS patients receiving antiretroviral treatment in Dehong, Yunnan province

收稿日期:2016-01-15 出版日期:2016-07-15

DOI：10.3760/cma.j.issn.0254-6450.2016.07.009

中文关键词: 艾滋病患者抗病毒治疗耐药性德宏州

英文关键词: AIDS patients antiretroviral treatment Resistance Dehong prefecture

基金项目:国家自然科学基金项目（81373062）；国家科技重大专项（2012ZX10001001004，2013ZX10004906）；国家重点地区艾滋病防治项目

作者	单位	E-mail
姚仕堂	678400 芒市, 德宏州疾病预防控制中心艾滋病性病防治科
姚媛	200032上海, 复旦大学公共卫生学院流行病学教研室、公共卫生安全教育部重点实验室
时允	678400 芒市人民医院
李品银	678600 瑞丽市人民医院
许元武	678700 陇川县人民医院
杨文芹	679300 盈江县人民医院
章银娣	678400 芒市, 德宏州人民医院
尹春英	679200 梁河县人民医院
寸柳青	678300 盈江县中医院
翟志坚	678500 畹町医院
何纳	200032上海, 复旦大学公共卫生学院流行病学教研室、公共卫生安全教育部重点实验室	nhe@shmu.edu.cn
段松	678400 芒市, 德宏州疾病预防控制中心艾滋病性病防治科	dhduansong@sina.com.cn

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中文摘要:

目的了解云南省德宏州2012-2014年成年艾滋病患者抗病毒治疗耐药发生情况及其影响因素。方法采用队列研究方法，对2012年底在云南省德宏州接受抗病毒治疗半年及以上≥15岁的3 715例艾滋病患者，随访观察治疗12个月及24个月时的耐药发生情况。结果 3 715例患者以男性（56.6%）、26～45岁（72.6%）、已婚（76.0%）为主。感染途径主要是性传播（75.3%），基线治疗方案以奈韦拉平（NVP）+拉米夫定（3TC）+齐多夫定（AZT）组合相对较多（38.2%）。随访期间至少接受过一次HIV病毒载量检测的患者共3 556例（95.7%），其中至少出现一次血浆病毒载量≥1 000 拷贝/ml者253例（7.1%），均接受耐药检测，其中211例（83.4%）进行了耐药相关基因位点突变检测并有82例（38.9%）出现不同程度的耐药。2013年新发耐药52例，总人群新发耐药率为1.43/100人年；2014年新发耐药30例，总人群新发耐药率为0.88/100人年；整个队列的2年随访期间总新发耐药率为1.13/100人年。多因素logistic回归分析显示：年龄≤25岁、吸毒传播、基线治疗方案为D4T+3TC+NVP和基线CD₄⁺T淋巴细胞（CD₄）计数≤200个/μl者耐药发生率比年龄>25岁、性途径传播、基线治疗方案为NVP+3TC+AZT和基线CD₄计数≥351 个/μl者高，差异有统计学意义。耐药患者中共发现11种HIV基因亚型，以CRF_BC（31.7%）、CRF01_AE（22.0%）、C亚型（19.5%）占多数，其中CRF_BC/B’亚型、CRF_BC/CRF_01B亚型和CRF_BC/C亚型为混合病毒亚型的耐药者。耐药患者多数对NRTIs和NNRTIs耐药，耐药突变位点分别以M184V和K103N为主。结论云南省德宏州成年患者抗病毒治疗新发耐药率相对较低，但对于年龄较小和吸毒传播者应加强抗病毒治疗依从性教育，及时监测耐药发生。

英文摘要:

Objective To investigate the incidence of drug resistance in adult AIDS patients receiving antiretroviral treatment (ART) and influencing factors in Dehong prefecture, Yunnan province during 2012-2014. Methods For this cohort study, all the AIDS patients aged over 15 and receiving ART in Dehong were screened for HIV drug resistance in 2012, and 3 715 patients who had received ART for more than 6 months were enrolled for 12 months and 24 months follow up. Results Among the 3 715 patients, 56.6% were males, 72.6% were aged 26-45 years and 76.0% were married. The main treatment regimen was nevirapine (NVP)+lamivudine (3TC)+zidovudine (AZT) (38.2%). A total of 3 556 patients (95.7%) received at least one viral load testing during the two years follow-up, among them 253 (7.1%) patients had VL≥1 000 copies/ml, in which 211 (83.4%) received drug resistance related gene mutation testing, the results indicated that the drug resistance developed in 52 and 39 patients in 2013 and 2014 (1.43 per 100 person years and 0.88 per 100 person years) respectively. The overall HIV drug incidence was 1.13 per 100 person years. Multivariate regression analysis indicated that age≤25 years, to be infected through drug use, treatment regimen as D4T+3TC+NVP and baseline CD₄⁺T cells≤200 cells/μl were the risk factor of HIV drug resistance. Eleven HIV gene subtypes were detected in the 82 patients with newly developed drug resistance, CRF_BC was predominant (31.7%), followed by CRF01_AE (22.0%) and C (19.5%). Ten patients were infected with mixed subtypes of CRF_BC/B', CRF_BC/CRF_01B and CRF_BC/C. Most of the 82 patients were resistant to NRTIs and NNRTIs, the main mutation loci were M184V and K103N. Conclusions The incidence of drug resistance in adult AIDS patients receiving ART was relatively low in Dehong. However, it is necessary to conduct the health education in young people and drug users to improve the treatment compliance and strengthen the surveillance for HIV drug resistance.

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