2014-2016年无锡市HIV/AIDS耐药突变分析

陈剑双; 殷玥琪; 成浩; 张轩; 袁德富; 张晓轩; 王晓敏; 魏乾坤; 王蓓

doi:10.16462/j.cnki.zhjbkz.2021.06.016

2014-2016年无锡市HIV/AIDS耐药突变分析

doi: 10.16462/j.cnki.zhjbkz.2021.06.016

1.
210009 南京，东南大学公共卫生学院流行病与卫生统计学系
2.
214028 无锡，新吴区疾病预防控制中心急性传染病防治科
3.
214000 无锡，无锡市疾病预防控制中心疾病控制部

基金项目:

江苏省研究生科研与实践创新计划 KYCX17_0184

江苏省青年学生HIV-1感染传播的分子网络分析及社会网络探索 0701-184160070478

详细信息

通讯作者:
王蓓，E-mail：wangbeilxb@163.com

中图分类号: R181.8
计量
- 文章访问数: 460
- HTML全文浏览量: 253
- PDF下载量: 53
- 被引次数: 0
出版历程
- 收稿日期: 2020-11-11
- 修回日期: 2021-01-07
- 刊出日期: 2021-06-10

Analysis of HIV/AIDS drug resistance mutations in Wuxi City from 2014 to 2016

1.
Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing 210009, China
2.
Department of Acute Infectious Diseases Prevention and Control, Xinwu District Center for Disease Prevention and Control, Wuxi 214028, China
3.
Department of Disease Control, Wuxi Center for Disease Prevention and Control, Wuxi 214000, China

Funds:

Jiangsu Postgraduate Scientific Research and Practice Innovation Program KYCX17_0184

Molecular network analysis and social network exploration of HIV-1 infection among young students in Jiangsu Province 0701-184160070478

More Information

Corresponding author: WANG Bei, E-mail: wangbeilxb@163.com

摘要

摘要: 目的了解江苏省无锡市2014-2016年随访的HIV感染者或AIDS患者(HIV/AIDS)HIV基因水平耐药变化特征。方法以2014年无锡市HIV/AIDS人群为研究对象，开展HIV分子流行病学调查及随访研究。收集感染者的基本信息，并从其血液样本中提取DNA，通过nest-PCR扩增pol基因片段并测序，将pol序列提交至HIV耐药数据库进行耐药突变位点分析。2016年随访相同人群，再次检测人类免疫缺陷病毒-1型(human immunodeficiency virus-1，HIV-1)耐药突变情况，分析两年间耐药变化情况。结果在2014-2016年共整理收集HIV/AIDS者612例，年龄主要集中在30岁及以上，占比85.46%(523/612)，其中≥50岁人群比例较高，占比37.26%(228/612)。传播途径以同性性传播为主，占49.68%(304/612)。共检测1 224例样本，成功获得811条pol序列，检出总耐药率为10.11%(82/811)，对非核苷类反转录酶抑制剂(non-nucleoside reverse transcriptase inhibitors, NNRTIs)、核苷类反转录酶抑制剂(nucleoside reverse transcriptase inhibitors, NRTIs)和蛋白酶抑制剂(protease inhibitors, PIs)的耐药率分别为7.77%(63/811)、5.30%(43/811)和1.23%(10/811)。最常见的耐药突变位点是K103N/S和M184V/I。共有38例HIV/AIDS感染者随访前后耐药结果发生变化。结论无锡市HIV/AIDS感染者HIV-1基因水平耐药多样且复杂，耐药变化较大，应继续加强耐药突变监测及抗病毒治疗管理。
- HIV感染者 /
- 艾滋病患者 /
- 耐药突变
Abstract: Objective To investigate the characteristics of HIV gene drug resistance changes among human immunodeficiency virus infected person /acquired immune deficiency syndrome patients (HIV/AIDS) in Wuxi City, Jiangsu Province from 2014 to 2016. Methods The HIV/ AIDS population in Wuxi City in 2014 was used as the research object to carry out HIV molecular epidemiological investigation and follow-up research. Basic information of the infected persons were collected, and DNA was extracted from their blood samples. The pol gene fragment was amplified by nest-PCR and sequenced. The sequence was then submitted to the HIV drug resistance database for drug resistance mutation analysis. In 2016, the same population was followed up. The HIV-1 drug resistance mutation was tested again, and the change of drug resistance during two years was analyzed. Results A total of 612 HIV/AIDS cases from 2014 to 2016 were collected. Most of them were aged 30 or above, accounting for 85.46% (523/612), among which the proportion of people aged 50 or older was higher, accounting for 37.25% (228/612). The main route of transmission was homosexual transmission, accounting for 49.67% (304/612). A total of 1 224 samples were tested and 811 pol sequences were successfully obtained. The total resistance rate was 10.11% (82/811). The drug resistance rates to non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors and protease inhibitors were 7.77% (63/ 811), 5.30% (43 /811) and 1.23% (10/811), respectively. The most common mutations were K103N/S and M184V/I. A total of 38 cases of HIV/AIDS had changes in drug resistance before and after follow-up. Conclusion The drug resistance of human immunodeficiency virus-1 (HIV-1) gene level of HIV/AIDS patients in Wuxi was diverse and complex, and the drug resistance changed greatly. Therefore, the monitoring of drug-resistant mutations and the management of antiviral treatment should be strengthened.
- HIV infected person /
- AIDS patients /
- Drug resistance variation

HTML全文

图 1 2014年无锡市HIV/AIDS中HIV-1耐药突变情况

Figure 1. Drug resistant mutations of HIV-1 in HIV/AIDS in Wuxi City in 2014

下载: 全尺寸图片幻灯片

图 2 2016年无锡市HIV/AIDS中HIV-1耐药突变情况

Figure 2. Drug resistant mutations of HIV-1 in HIV/AIDS in Wuxi City in 2016

下载: 全尺寸图片幻灯片

表 1 2014年无锡市612例HIV/AIDS感染者的基本人口学特征

Table 1. Demographic characteristics of 612 HIV/AIDS patients in Wuxi City in 2014

研究对象特征	频数	百分比(%)
性别
男	515	84.15
女	97	15.85
年龄^a(岁)
< 30	89	14.54
30~ < 40	160	26.14
40~ < 50	135	22.06
≥50	228	37.26
婚姻状况
未婚	175	28.60
已婚有配偶	230	37.58
离婚或丧偶	207	33.82
文化程度
大专及以上	129	21.08
高中或中专	174	28.43
初中	224	36.60
小学	80	13.07
文盲	5	0.82
感染途径
同性传播	304	49.68
异性传播	289	47.22
注射毒品	7	1.14
血液传播	3	0.49
其他	9	1.47
CD4细胞^b(个/μl)
≥350	396	64.71
< 350	216	35.29
抗病毒治疗^c
否	66	10.78
是	546	89.22
确诊到治疗时间(年)
< 1	348	56.86
1~ < 2	91	14.87
2~ < 3	55	8.98
3~ < 4	30	4.90
≥4	22	3.59
注：^a年龄：2016年612例HIV/AIDS的年龄; ^b CD4细胞：2016年612例HIV/AIDS的CD4细胞计数水平; ^c抗病毒治疗：2016年612例HIV/AIDS抗病毒治疗情况。

下载: 导出CSV

表 2 2014-2016年无锡市HIV/AIDS感染者耐药变化情况

Table 2. Changes of drug resistance in HIV/AIDS patients in Wuxi City from 2014 to 2016

编号	抗病毒治疗		耐药药物	耐药位点		耐药程度	亚型	CD4细胞(个/μl)
编号	2014年	2016年	耐药药物	2014年	2016年	耐药程度	亚型	2014年	2016年
wx1	是	是	NRTI	T215N		低	01_AE	445	470
wx2	是	是	NRTI	M184V	D67N, M184I	低	B	512	422
wx3	是	是	NRTI	M184V		高	01_AE	641	695
wx4	是	是	NRTI	D67N, T69D, K70R, M184V, T215F, K219Q	M184V	高	01_AE	267	688
wx5	否	是	NNRTI	V179F		低	01_AE	284	368
wx6	是	是	NNRTI	G190A		高	01_AE	40	202
wx7	是	是	NNRTI	G190E		高	01_AE	437	1 424
wx8	是	是	NRTI	M184V		高	01_AE	123	320
			NNRTI	K103N		高
wx9	是	是	NRTI	M184I		高	B	202	194
			NNRTI	V106I, E138K, M230I		高
wx10	是	是	NRTI	K65R, Y115F		高	01_AE	11	173
			NNRTI	K101E, E138K, G190V, H221Y	E138K	高
wx11	是	是	PI		I54V	低	01_AE	306	291
wx12	是	是	NRTI		M184V	高	08_BC	630	707
wx13	是	是	NRTI		M184I	高	01_AE	323	419
wx14	否	否	NRTI		T215I	低	01_AE/07_BC	843	68
wx15	是	是	NRTI		Y115F, T215I	高	01_AE	681	447
wx16	是	是	NNRTI		V108I	低	68_01B	375	596
wx17	否	是	NNRTI		M230I	中	07_BC	244	472
wx18	是	是	NNRTI		M230I	中	01_AE	137	238
wx19	是	是	NNRTI		M230I	中	01_AE	449	562
wx20	是	是	NNRTI		M230I	中	67_01B	98	93
wx21	是	是	NNRTI		V179D	中	01_AE	99	73
wx22	是	是	NNRTI		V179E, M230I	中	55_01B	380	578
wx23	否	是	NNRTI		K103N	高	01_AE	290	450
wx24	否	是	NNRTI		K103N	高	01_AE	117	95
wx25	是	是	NNRTI		K103N	高	B	320	716
wx26	是	是	NNRTI		K103N	高	01_AE	291	449
wx27	是	是	NNRTI		K103N	高	01_AE	144	222
wx28	是	是	NNRTI		K103N	高	01_AE/B	458	466
wx29	是	是	NNRTI		K103N	高	01_AE	418	487
wx30	是	是	NNRTI		G190E	高	01_AE	717	738
wx31	是	是	NNRTI		G190S	高	01_AE	223	369
wx32	是	是	NNRTI		Y181C, G190A	高	01_AE	183	262
wx33	是	是	NRTI		M184I	高	01_AE	1 087	1 406
			NNRTI		M230I	中
wx34	是	是	NRTI		M184I	高	07_BC	339	746
			NNRTI		M230I	中
wx35	是	是	NRTI		M184I	高	B	423	413
			NNRTI		M230I	中
wx36	是	是	NRTI		M184I	高	01_AE	353	429
			NNRTI		E138K, M230I	高
wx37	是	是	NRTI		M184I	高	01_AE	653	315
			NNRTI		V106M, M230I	高
wx38	否	是	NRTI		D67N, K70E, M184I	高	67_01B	8	163
			NNRTI		A98G, K103N, Y181C, P225H	高

下载: 导出CSV

参考文献(19)

[1]	Guan X, Han M, Li ZJ, et al. HIV-1 genetic diversity and transmitted drug resistance among newly diagnosed HIV-1 individuals in Jiangmen[J/OL]. (2020-03-01)[2020-10-20]. https://doi.org/10.1002/jmv.25741.
[2]	Yang ZJ, Wei SG, Liu JJ, et al. Characterization of HIV-1 subtypes and drug resistance mutations in Henan Province, China (2017-2019)[J]. Arch Virol, 2020, 165(6): 1453-1461. DOI: 10.1007/s00705-020-04606-6.
[3]	Han XS, Jemal A, Hulland E, et al. HIV infection and survival of lymphoma patients in the era of highly active antiretroviral therapy[J]. Cancer Epidemiol Biomarkers Prev, 2017, 26(3): 303-311. DOI: 10.1158/1055-9965.EPI-16-0595.
[4]	Phillips AN, Cambiano V, Miners A, et al. Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment: modelling study and economic analysis[J]. Lancet HIV, 2014, 1(2): e85-e93. DOI: 10.1016/S2352-3018(14)70021-9.
[5]	Lakhikumar SA, Ramsing ST, Ranjana DK, et al. Prevalence of drug resistance associated mutations among the anti retroviral therapy exposed HIV-1 infected individuals in Manipur, Northeast India[J]. Curr HIV Res, 2016, 14(4): 360-370. DOI: 10.2174/1570162x14666160401131426.
[6]	Schultze A, Phillips AN, Paredes R, et al. HIV resistance testing and detected drug resistance in Europe[J]. AIDS, 2015, 29(11): 1379-1389. DOI: 10.1097/QAD.0000000000000708.
[7]	Wu J, Norris J, Liu HX, et al. The prevalence of HIV drug resistance among treatment-failure individuals and treatment-naive individuals in China: a meta-analysis[J]. Biomed Environ Sci, 2014, 27(11): 858-871. DOI: 10.3967/bes2014.123.
[8]	Baxter JD, Dunn D, White E, et al. Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial[J]. HIV Med, 2015, 16 Suppl 1(1): 77-87. DOI: 10.1111/hiv.12236.
[9]	袁瑞, 成浩, 陈璐斯, 等. 无锡市HIV-1毒株耐药基因突变的调查研究[J]. 中华疾病控制杂志, 2016, 20(12): 1216-1220. DOI: 10.16462/j.cnki.zhjbkz.2016.12.008. Yuan R, Cheng H, Chen LS, et al. A survey on drug-resistance gene mutations in HIV-1 strains in Wuxi City[J]. Chin J Dis Control Prev, 2016, 20(12): 1216-1220. DOI: 10.16462/j.cnki.zhjbkz.2016.12.008.
[10]	Gartner MJ, Roche M, Churchill MJ, et al. Understanding the mechanisms driving the spread of subtype C HIV-1[J]. EBioMedicine, 2020, 53: 102682. DOI: 10.1016/j.ebiom.2020.102682.
[11]	殷玥琪, 陈剑双, 成浩, 等. 无锡市2013-2016年HIV-1亚型及进化分析[J]. 中华流行病学杂志, 2020, 41(2): 244-245. DOI: 10.3760/cma.j.issn.0254-6450.2020.02.019. Yin YQ, Chen JS, Cheng H, et al. Transition and evolution of HIV-1 subtype among HIV-1 infections in Wuxi City, 2013-2016[J]. Chin J Epidemiol, 2020, 41(2): 244-245. DOI: 10.3760/cma.j.issn.0254-6450.2020.02.019.
[12]	Yin YQ, Liu YX, Zhu J, et al. The prevalence, temporal trends, and geographical distribution of HIV-1 subtypes among men who have sex with men in China: a systematic review and meta-analysis[J]. Epidemiol Infect, 2019, 147(2): e83. DOI: 10.1017/S0950268818003400.
[13]	李梅, 李俊刚, 罗福龙, 等. 重庆市2014年至2018年人类免疫缺陷病毒1型感染者的耐药突变分析[J]. 中华传染病杂志, 2020, 38(5): 283-287. DOI: 10.3760/cma.j.cn311365-20191010-00322. Li M, Li JG, Luo FL, et al. Analysis of drug-resistant mutations in human immunodeficiency virus-1 infected patients in Chongqing City from 2014 to 2018[J]. Chin J Infect Dis, 2020, 38(5): 283-287. DOI: 10.3760/cma.j.cn311365-20191010-00322.
[14]	殷玥琪, 朱靖, 吴楠楠, 等. 中国MSM人群中HIV-1亚型与不同位点耐药突变发生频率的Meta分析[J]. 中华疾病控制杂志, 2017, 21(6): 622-626. DOI: 10.16462/j.cnki.zhjbkz.2017.06.020. Yin YQ, Zhu J, Wu NN, et al. The frequency of drug resistance mutations among different HIV-1 subtypes in Chinese MSM: a Meta-analysis[J]. Chin J Dis Control Prev, 2017, 21(6): 622-626. DOI: 10.16462/j.cnki.zhjbkz.2017.06.020.
[15]	Ndongmo TN, Ndongmo CB, Michelo C. Sexual and reproductive health knowledge and behavior among adolescents living with HIV in Zambia: a case study[J]. Pan Afr Med J, 2017, 26: 71. DOI: 10.11604/pamj.2017.26.71.11312.
[16]	Gregson J, Rhee SY, Datir R, et al. Human immunodeficiency virus-1 viral load is elevated in individuals with reverse-transcriptase mutation M184V/I during virological failure of first-line antiretroviral therapy and is associated with compensatory mutation L74I[J]. J Infect Dis, 2020, 222(7): 1108-1116. DOI: 10.1093/infdis/jiz631.
[17]	Di Vincenzo P, Rusconi S, Adorni F, et al. Prevalence of mutations and determinants of genotypic resistance to etravirine (TMC125) in a large Italian resistance database (ARCA)[J]. HIV Med, 2010, 11(8): 530-534. DOI: 10.1111/j.1468-1293.2009.00819.x.
[18]	李敬云. HIV-1的耐药基因突变[J]. 中国艾滋病性病, 2010, 16(2): 195-197. DOI: 10.13419/j.cnki.aids.2010.02.011. Li JY. HIV-1 drug resistance mutations[J]. Chin J AIDS STD, 2010, 16(2): 195-197. DOI: 10.13419/j.cnki.aids.2010.02.011.
[19]	Gupta RK, Hill A, Sawyer AW, et al. Virological monitoring and resistance to first-line highly active antiretroviral therapy in adults infected with HIV-1 treated under WHO guidelines: a systematic review and meta-analysis[J]. Lancet Infect Dis, 2009, 9(7): 409-417. DOI: 10.1016/S1473-3099(09)70136-7.