發(fā)布時(shí)間：2018-02-10 07:50

  本文關(guān)鍵詞： 越南 HIV流行亞型 耐藥突變　出處：《廣西醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的通過(guò)獲得越南東北部四省接受抗病毒治療人群的HIV-1 pol區(qū)序列,以期了解HIV毒株在越南北部的亞型分布和耐藥特征。方法通過(guò)方便抽樣,在越南北部廣寧省,諒山省,高平省和何江省HIV-1流行嚴(yán)重地區(qū)選取接受抗病毒治療的HIV感染者或患者作為研究對(duì)象。對(duì)研究對(duì)象進(jìn)行流行病學(xué)調(diào)查,采集外周靜脈血液10ml,提取血細(xì)胞前病毒DNA,采用巢式PCR對(duì)HIV-1 pol基因片段進(jìn)行擴(kuò)增,將陽(yáng)性擴(kuò)增產(chǎn)物送北京博邁德公司進(jìn)行Sanger法測(cè)序,然后采用Bioedit、Chromas和MEGA等相關(guān)生物學(xué)軟件對(duì)所得序列進(jìn)行序列的比對(duì)校正、亞型分析。最后采用Spss 16.0軟件對(duì)所得數(shù)據(jù)進(jìn)行統(tǒng)計(jì)分析。結(jié)果 1.本次研究共招募433例感染者,采集自越南北部的4個(gè)省份,包括高平(112例)、河江(121例)、諒山(96例)、廣寧(104例),分別占25.87%、27.94%、22.17%、24.02%,納入研究的HIV-1感染者均接受高效抗逆轉(zhuǎn)錄病毒治療;其中男性247例,占57.04%,男女比例為1.33:1;平均年齡為(38.52±8.18)歲,以25-50歲居多;婚姻狀況以已婚、離異或喪偶、未婚為主,分別占61.66%、19.63%和14.55%;文化程度以初中以上學(xué)歷為主,占88.91%;傳播途徑以注射吸毒為主,占52.66%,其次為異性性傳播,占26.33%。2.本研究共收集433例HIV-1感染者的血漿樣本,成功擴(kuò)增出206例感染者的HIV-1 pol基因序列,測(cè)序進(jìn)行基因分型,系統(tǒng)進(jìn)化樹顯示206例樣本均為CRF01_AE亞型。3.對(duì)獲得的206例CRF01_AE亞型HIV-1毒株進(jìn)行基因型耐藥性分析,結(jié)果顯示有32例樣本至少對(duì)一種抗病毒藥物,其中19例樣本同時(shí)對(duì)NRTIs和NNRTIs類藥物耐藥,總耐藥率為15.53%(32/206)。在32例耐藥樣本中,注射吸毒途徑為13例(13.40%),異性性傳播為8例(12.31%)。4.耐藥率在不同省間的分布有差異,耐藥發(fā)生率最高的是諒山省和廣寧省,均占23.08%,其次是河江省(16.39%)、高平省(5.97%)。5.本次研究獲得32例耐藥毒株,其中NNRTIs和NRTIs雙重耐藥毒株最多,為19例,占59.38%;其次分別為NNRTIs(8例)、NRTIs(3例)和PIs(2例),分別占25.00%、9.38%和6.25%。6.在NNRTIs耐藥的樣本中,以181、190、230、179位置突變?yōu)橹?其中突變位點(diǎn)Y181C、G190A、M230I和V179D分別占所有突變位點(diǎn)總數(shù)的19.40%、13.43%、13.43%和10.45%,共56.71%,占比超過(guò)其他突變位點(diǎn)總和(43.29%);其他位置如101、103、225等有少量分布。在NRTIs耐藥的樣本中,以184、75、215、41、65位置突變?yōu)橹?其中突變位點(diǎn)M184V、V75M、T215F、M41L、K65R分別占所有突變位點(diǎn)總數(shù)的14.29%、10.00%、10.00%、8.57%、7.14%。在PIs耐藥的樣本中,以突變位點(diǎn)G73S(55.56%)居多,其他為I84V、K43T、L89V、L90M。7.統(tǒng)計(jì)學(xué)結(jié)果分析顯示,NNRTIs不同藥物的耐藥程度差異有統(tǒng)計(jì)學(xué)意義(χ2=37.248,P0.001),NNRTIs耐藥以中、高度耐藥為主,占到總數(shù)的81.6%;中度耐藥以ETR(26.19%)、RPV(38.10%)居多,高度耐藥以EFV(28.57%)、NVP(42.86%)居多。NRTIs不同藥物的耐藥程度差異有統(tǒng)計(jì)學(xué)意義(χ2=39.445,P0.001),NRTIs耐藥以高度耐藥為主,約占到總數(shù)三分之二;高度耐藥以FTC(29.57%)、3TC(29.51%)居多,其次是DDI(13.11%)、ABC(9.84%)、D4T(9.84%)、AZT(4.92%)、TDF(3.28%)。PIs不同藥物的耐藥程度差異無(wú)統(tǒng)計(jì)學(xué)意義(χ2=3.773,P=1.000)。影響耐藥發(fā)生的logistics回歸多因素分析,結(jié)果表明,樣本來(lái)源于諒山和廣寧省是基因型耐藥發(fā)生的危險(xiǎn)因素(P0.05)。結(jié)論:越南東北部四省的流行的HIV毒株以CRF01_AE亞型為主;東北部四省的抗病毒治療人群HIV發(fā)生耐藥突變率高于全越南其他地區(qū),主要對(duì)NNRTIs和NRTIs藥物耐藥為主。
[Abstract]:Objective to sequence HIV-1 pol District in northeastern Vietnam four provinces receive antiviral treatment groups, in order to understand the HIV strains in northern Vietnam subtype distribution and drug resistance characteristics. By convenient sampling, Guangning Province in northern Vietnam, Lang Son Province, Gaoping province and Zhejiang Province HIV-1 epidemic area were receiving antiretroviral treatment of HIV infected persons or patients as the research object. Epidemiological survey was conducted on the research object, collected peripheral venous blood 10ml extracted from blood cells before virus DNA by nested PCR for HIV-1 pol gene fragment was amplified, the positive PCR products were sent to Beijing Bomaide company Sanger sequencing, and then using Bioedit, Chromas and MEGA and other related correction ratio biological software sequence in the sequence and subtype analysis. Finally, using Spss 16 statistical software to analysis the data. The results of this study to recruit a total of 1. Raised 433 cases of infection, 4 provinces gathered from more North and south, including Gaoping (112 cases), river (121 cases), Lang Son (96 cases), Guangning (104 cases), respectively 25.87%, 27.94%, 22.17%, 24.02%, HIV-1 infection were included in the study on HAART treatment; 247 cases were male, accounting for 57.04%, the ratio of male to female was 1.33:1; the average age was (38.52 + 8.18) years old, with 25-50 years of age; marital status to married, divorced or widowed, unmarried accounted for 61.66%, 19.63% and 14.55%; education in junior high school or above is the main route of transmission, accounting for 88.91%; mainly by injection drug use accounted for 52.66%, followed by heterosexual transmission accounted for 26.33%.2., plasma samples were collected for the study of 433 cases of HIV-1 infection, and successfully amplified the HIV-1 sequence of pol gene in 206 cases of infection, sequencing, genotyping, phylogenetic analysis showed that 206 cases were CRF01_AE subtype samples for.3. 206 cases of C RF01_AE subtype HIV-1 strains were genotype drug resistance analysis, results showed that 32 samples of at least one of antiviral drugs, including 19 cases of samples at the same time on NRTIs and NNRTIs drug resistance, total drug resistance rate was 15.53% (32/206). In 32 cases of drug samples, drug injection way for 13 cases (13.40%), specificity the spread of 8 cases (12.31%).4. resistance rate differences in the distribution of different province, the resistance rate is the highest in Lang Son province and Guangning Province, accounted for 23.08%, followed by the river province (16.39%), Gaoping province (5.97%).5. in this study were obtained from 32 patients with drug-resistant strains, including NNRTIs and NRTIs double resistant strains up to 19 cases, accounting for 59.38%; followed by NNRTIs (8 cases), NRTIs (3 cases) and PIs (2 cases), respectively 25%, 9.38% and 6.25%.6. in NNRTIs resistant samples, with 181190230179 point mutations, including mutations of Y181C, G190A, M230I and V179D respectively. For all Mutations in 19.40% of the total, 13.43%, 13.43% and 10.45%, a total of 56.71%, accounting for more than the sum of the other mutations (43.29%); other positions such as 101103225. A small amount of distribution in NRTIs resistant samples, 184,75215,41,65 mutation position, the mutation sites of M184V, V75M, T215F, M41L, K65R respectively in all mutant the total number of sites 14.29%, 10%, 10%, 8.57%, 7.14%. in PIs resistant samples, the mutation sites of G73S (55.56%) are the other for I84V, K43T, L89V, L90M.7. statistical analysis indicated that there were statistically significant differences in degree of resistance to NNRTIs of different drugs (2=37.248, P0.001), NNRTIs resistance to, highly resistant, accounting for 81.6% of the total; moderate resistance to ETR (26.19%), RPV (38.10%) are highly resistant to EFV (28.57%), NVP (42.86%).NRTIs are not the same degree of drug resistance was statistically significant (2=39.445, P0.001), The resistance of NRTIs to highly resistant, accounting for about 2/3 of the total number of highly resistant to; FTC (29.57%), 3TC (29.51%) majority, followed by DDI (13.11%), ABC (9.84%), D4T (9.84%), AZT (4.92%), TDF (3.28%) there was no significant difference in different degree of resistance to drugs (.PIs x 2=3.773, P=1.000). Impact analysis, multiple regression results show that the resistance of logistics, samples from Lang Son and Guangning province are risk factors for the occurrence of resistant genotypes (P0.05). Conclusion: the northeastern province of Vietnam four epidemic HIV strains to CRF01_AE subtype; four northeastern Province antiviral treatment population the occurrence of HIV resistance mutation rate was higher than that in other areas throughout the country, mainly on the NNRTIs and NRTIs drug resistance.

【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R512.91;R181.3

【參考文獻(xiàn)】

相關(guān)期刊論文 前7條

1 潘沛江;韋富梅;蔣俊俊;梁冰玉;黃頡剛;廖艷研;蘇錦明;李_g;楊小藝;陳暉;葉力;梁浩;;阿片類毒品對(duì)HIV-1感染者PBMCs中TLR9基因表達(dá)的影響[J];病毒學(xué)報(bào);2015年02期

2 張星燦;吳瓊海;沈偉偉;丁盈盈;林海江;何納;;浙江省臺(tái)州地區(qū)新確診HIV感染者耐藥突變研究[J];中華疾病控制雜志;2015年02期

3 楊洪;蘇玲;王啟興;袁丹;秦光明;劉紅露;梁姝;肖林;楊文;;涼山州部分彝族人群2011年HIV耐藥警戒線監(jiān)測(cè)研究[J];中國(guó)艾滋病性病;2015年01期

4 梁冰玉;楊小藝;蔣俊俊;周波;陳暉;陳榮鳳;趙芳凝;潘沛江;黃頡剛;葉力;梁浩;;廣西壯族自治區(qū)海洛因成癮的HIV感染者和艾滋病患者抗病毒治療效果及耐藥性分析[J];中華預(yù)防醫(yī)學(xué)雜志;2014年10期

5 王欣;程紹輝;;HIV整合酶抑制劑的應(yīng)用及耐藥研究進(jìn)展[J];中國(guó)艾滋病性病;2012年06期

6 梁冰玉;李敬云;莊道民;蘇齊鑒;劉思揚(yáng);肖信;岑平;陳暉;梁浩;蔣俊俊;;嗎啡對(duì)HIV-1在MT2細(xì)胞和巨噬細(xì)胞中復(fù)制的影響[J];中華檢驗(yàn)醫(yī)學(xué)雜志;2011年07期

7 史衛(wèi)國(guó);賈啟燕;劉克良;;HIV-1融合抑制劑研究現(xiàn)狀及發(fā)展趨勢(shì)[J];藥學(xué)學(xué)報(bào);2010年02期

，

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