河北省HIV-1分子流行病学和耐药基因变异研究

发布时间：2018-05-07 01:36

本文选题：人类免疫缺陷病毒 + 基因型　；参考：《河北大学》2017年博士论文

【摘要】：河北省位于中国华北地区,环绕京津,自古是京畿要地,是进入首都北京的门户,南部与河南省相邻。自1989年从国外务工回国人员当中确认首例艾滋病例以来,河北省经过二十世纪九十年代中期在廊坊献血人群和邢台受血人群中爆发艾滋病疫情后,新诊断HIV/AIDS病例呈现逐年上升的趋势,截止到2015年底全省累计报告HIV/AIDS患者7303例。27年来,HIV-1在河北省的流行传播人群已经发生改变,2005年以后,性接触已经替代血液传播,成为河北省艾滋病疫情发展的最主要途径。本研究首先对河北省HIV-1的总体流行形式进行了分析,并以2013年全年新诊断报告且未治疗的HIV-1阳性病例为研究对象,实施了目前国内针对一个省份的最广泛的HIV-1分子流行病学调查,分析了新诊断病例中HIV-1耐药毒株及其流行。并且研究了16-25岁青少年人群和男男性接触传播人群(MSM)中HIV-1流行及传递性耐药(TDR)突变,有利于预测和观察河北省HIV-1的整体流行变化。研究成果主要包括以下几个方面。1.河北省新诊断HIV-1阳性病例逐年上升,经性行为传播持续成为HIV扩散的主要途径,特别是男男同性接触感染快速上升,成为我省HIV疫情上升的主要途径。2.基于HIV-1 gag全长基因-pol部分基因序列,2013年共发现有9种HIV-1基因型正在河北省内流行。前四个主要基因型是CRF01_AE(53.4%)、CRF07_BC(23.4%)、subtype B(15.9%)和新的独特型重组体(URFs,4.9%)。一年内,以前河北省内未曾证实存在的三种基因型(subtype A1、CRF55_01B和CRF65_cpx)首次在MSM人群中被发现。发现所有9种基因型均已在性接触传播人群中传播。30个URFs毒株通过6种基因重组模式形成,包括CRF01_AE/BC(40.0%)、CRF01_AE/B(23.3%)、B/C(16.7%)、CRF01_AE/C(13.3%)、CRF01_AE/B/A2(3.3%)和CRF01_AE/BC/A2(3.3%),并且证实在30个URFs中流行着2个潜在的流行性毒株(pCRF)。分子进化分析显示河北省的流行毒株通过多种渠道从我国西南和南部省份、邻省等经多次传入河北,特别是与北京、辽宁等邻省以MSM为主的性传播人群之间存在4个较大的CRF01_AE(2个)、subtype B(1个)和CRF07_BC(1个)流行簇,具有紧密的传播关系。河北省内流行的所有9种HIV-1基因型已经通过性接触特别是MSM从其原有的高危人群传入普通人群。3.在河北省5个MSM监测点中共发现50例新发感染HIV-1阳性病例。通过对其HIV-1 gag(46条)、pol(48条)和env(45条)基因序列的综合分析发现四种基因型,即CRF01_AE(56.0%)、CRF07_BC(30.0%)、subtype B(12.0%)和URFs(6.0%)。URFs的3种重组模式被确认,即CRF01_AE/BC、CRF01_AE/B和CRF01_AE/C。Subtype B和CRF01_AE毒株与邻省传播关系紧密。监测点新发感染MSM人群中HIV-1主要流行趋势与河北省整体流行趋势基本一致,因此通过MSM监测点可以观察河北省整体的HIV-1流行趋势。4.通过分析HIV-1 pol基因序列,2013年新诊断未治疗病例中总的耐药突变发生率为16.2%(109/672)。蛋白酶抑制剂(PIs)耐药突变率为6.3%(42/672),核苷类逆转录酶抑制剂(NRTIs)突变率为2.4%(16/672),非核苷类逆转酶抑制剂(NNRTIs)突变率为8.6%(58/672)。其中,两个不同基因编码区的双重突变率为0.7%(5/672)、三个基因编码区的多重突变率0.1%(1/672)和单基因编码区的多位点突变0.4%(3/672)。这种复杂的突变模式导致当前史坦福数据库所列药物中除了3TC、ABC、DDI、FTC和TDF五种NRTIs外,其他14种药物都产生了不同程度的耐药性,特别是导致所有的PIs和NNRTIs药物药效不同程度地降低。16-25岁青少年和MSM监测点新发感染病例中传递性耐药(TDR)发生率分别为6.6%和2.1%。分子进化分析发现HIV-1耐药毒株分布在不同的流行簇中,尤其是与邻省以MSM为主的大流行簇为HIV-1耐药毒株的传播创造了条件。
[Abstract]:Hebei province is located in North China, circling Beijing and Tianjin, is a Gyeonggi city from ancient times, is the gateway to the capital of Beijing, and the South and Henan province. Since 1989, since the first AIDS case was confirmed from the returnees from foreign workers abroad, Hebei province broke out in the Langfang blood donation crowd and the Xingtai blood crowd in the middle of 1990s. After the disease epidemic situation, the newly diagnosed HIV/AIDS cases showed a trend of increasing year by year. By the end of 2015, 7303 cases of HIV/AIDS patients were reported in the province for.27 years. The population of HIV-1 in Hebei province has changed. After 2005, sexual contact has replaced blood transmission, which has become the most important way for the development of AIDS epidemic in Hebei province. First, the general epidemic form of HIV-1 in Hebei province was analyzed. With the new diagnosis report of 2013 and the untreated HIV-1 positive cases, the most extensive HIV-1 molecular epidemiological survey in one province was carried out in China, and the HIV-1 resistant strain and its epidemic in the newly diagnosed cases were analyzed. The HIV-1 epidemic and transmissibility resistance (TDR) mutation in the 16-25 year old and male male contact population (MSM) were investigated, which was beneficial to the prediction and observation of the overall epidemic changes of HIV-1 in Hebei province. The research results mainly included the following aspects:.1. in Hebei Province, the new diagnostic HIV-1 positive cases increased year by year, and the sexual behavior spread continued to become a HIV expansion. The main approach, especially male male sex contact infection, has become the main route of the HIV epidemic in our province,.2. based on the HIV-1 gag full length gene -pol partial gene sequence. In 2013, 9 HIV-1 genotypes were found to be prevalent in Hebei province. The first four major genotypes were CRF01_AE (53.4%), CRF07_BC (23.4%), subtype B (15.9%). And a new idiotypic recombinant (URFs, 4.9%). Within a year, three genotypes (subtype A1, CRF55_01B and CRF65_cpx), which were not confirmed in previous Hebei Province, were discovered for the first time in the MSM population. All 9 genotypes have been transmitted through 6 gene recombination patterns, including CRF01_AE/B, of.30 URFs strains in sexual contact spread population. C (40%), CRF01_AE/B (23.3%), B/C (16.7%), CRF01_AE/C (13.3%), CRF01_AE/B/A2 (3.3%) and CRF01_AE/BC/A2 (3.3%), and confirmed that 2 potential pandemic strains (pCRF) were popular in 30 URFs. Molecular evolutionary analysis showed that the epidemic strains of Hebei province were introduced into Hebei many times through many channels from southwest and southern provinces of China, and other provinces. In particular, there are 4 larger CRF01_AE (2), subtype B (1) and CRF07_BC (1) cluster of sexually transmitted populations in the neighbouring provinces of Beijing and other provinces, which have close communication relations. All 9 HIV-1 genotypes popular in Hebei province have passed through sexual contact, especially MSM from their original high risk population, into the ordinary population.3 50 newly infected HIV-1 positive cases were found in 5 MSM monitoring sites in Hebei province. Through comprehensive analysis of its HIV-1 gag (46), pol (48) and env (45) gene sequences, four types of genotypes, namely, CRF01_AE (56%), CRF07_BC (30%), subtype B (12%) and URFs (6%).URFs, were identified. The relationship between B and CRF01_AE/C.Subtype B and CRF01_AE strains was closely related to the spread of neighboring provinces. The main trend of HIV-1 epidemic in the new infection MSM population of the monitoring point was basically the same as that of the whole epidemic trend in Hebei province. Therefore, the HIV-1 epidemic trend in Hebei province was observed through MSM monitoring points,.4. through the analysis of HIV-1 pol gene sequence, the new diagnosis was not treated in 2013. The total resistance mutation rate was 16.2% (109/672). The mutation rate of the protease inhibitor (PIs) was 6.3% (42/672), the nucleoside reverse transcriptase inhibitor (NRTIs) mutation rate was 2.4% (16/672), and the non nucleoside reverse enzyme inhibitor (NNRTIs) mutation rate was 8.6% (58/672). The double mutation rate of two different gene coding regions was 0.7% (5/6). 72) the multiple mutation rate 0.1% (1/672) and the multiple point mutation 0.4% (3/672) of the single gene coding region of the three gene coding regions. This complex mutation pattern leads to the other 14 drugs, in addition to five NRTIs, including 3TC, ABC, DDI, FTC and TDF in the current statf database. The drug efficacy of S and NNRTIs reduced the incidence of transmissibility resistance (TDR) in the new infection cases of.16-25 years old and MSM monitoring sites, respectively, and the incidence of TDR was 6.6% and 2.1%. molecular evolution analysis found that HIV-1 resistant strains were distributed in different epidemic clusters, especially the spread of MSM dominated pandemic clusters for HIV-1 resistant strains. The condition.

【学位授予单位】：河北大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R512.91

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