我国部分地区HIV-1耐药性毒株分子流行病学研究
发布时间：2018-09-19 19:24
【摘要】： HIV耐药性是指由于发生特定的病毒基因突变,导致病毒对药物敏感性下降的现象。大量研究显示,耐药性与抗病毒治疗效果之间存在显著的相关性,在控制了血浆病毒载量、CD4细胞计数和抗病毒治疗历史等因素以后,耐药性是独立的导致抗病毒治疗失败的因素。本研究通过对我国部分省份艾滋病病人的多次横断面研究,阐明在接受抗病毒治疗后,HIV-1耐药性毒株在不同时间点的发生和流行水平;以河南省某地的176名艾滋病患者为对象,通过5年的队列研究,分析针对不同药物的耐药发生的可能时间、耐药突变发生模式及其随时间的演变;了解在我国特有治疗模式下主要流行毒株中存在的新型耐药突变发生情况及pol区基因的多态性,最终为认识我国HIV-1耐药毒株的发生和流行规律、了解耐药性HIV-1毒株的分子进化特征、丰富对耐药相关突变的认识提供依据、为准确检测耐药毒株、提高艾滋病抗病毒治疗效果奠定基础。 第一部分我国部分地区HIV-1耐药性毒株流行的横断面研究 2004年3月至2008年9月,以河南、河北、山东、北京、广东、甘肃、宁夏及广西8省市的艾滋病病人为研究对象,进行多次横断面研究,其中河南连续监测5年,河北、山东、广西连续监测3年,北京、广东、甘肃连续监测2年,宁夏监测1年。通过病毒抑制率分析抗病毒治疗的效果;使用RT-PCR方法获得pol区目的基因,提交序列到斯坦福大学HIV耐药数据库获得耐药信息。共调查艾滋病患者1113名,累积研究2263人次,了解和掌握了抗病毒治疗地区治疗后病毒抑制和耐药发生情况。主要结果如下: 1.在监测省份,除河南省外,艾滋病抗病毒治疗均取得了良好的效果(病毒抑制率最高可达94.34%),延缓了艾滋病的进程; 2.耐药毒株在多个省份都有发生,但在河南呈高度流行趋势(约65%); 3.河南耐药监测人群中,服药依从性仅能维持75%左右,依从性差是导致该地区耐药毒株高发的直接原因; 4.耐药发生与抗病毒治疗失败之间呈高度相关(OR=0.942),耐药是导致抗病毒治疗失败的关键因素; 5.应加强治疗监管和抗病毒治疗教育、提高服药依从性,以延缓HIV-1耐药的发生与流行,提高治疗成功率。 第二部分河南省HIV-1耐药性毒株发生和流行的队列研究 当前我国已经开展了多次HIV耐药的横断面研究,但是队列研究还不多,在世界范围内也比较少见,而这样的研究对于揭示耐药的发生发展规律是非常重要的。我们对河南省某乡接受抗病毒治疗的艾滋病病人进行了5年开放式队列研究,通过分析不同时间点耐药突变出现的先后顺序、耐药突变发生和演变的模式等,分析在当地特殊治疗模式下,耐药性突变发生发展的规律。队列共纳入173例艾滋病患者,随访了1085人次、6510人月,最多的随访10次。主要结果如下: 1.服药依从性保持在75%左右的、使用AZT/DDI/NVP治疗方案的艾滋病患者,针对NRTIs发生耐药的时间中位数是抗病毒治疗后10个月左右,耐药发生高峰在治疗后6-12个月; 2.该监测人群针对NNRTIs耐药的发生时间中位数为治疗后6.5个月,在治疗后4-6个月耐药突变发生率最高。 3.首次发生的NRTIs耐药突变,早期(治疗1年内)发生的60%是单一位点突变,1年后以突变型形式出现的增多。NRTIs单一突变发生越晚,保持稳定或发展为突变型的可能性越大,对耐药的贡献也越大。首次发生的NRTIs耐药突变,如果是突变型,则多数导致中高度耐药。随治疗时间的延长,突变型出现并导致中高度耐药的概率呈上升趋势。 4.以单一位点形式出现的NNRTIs耐药突变,K103N最多(32.3%),Y181C(14.20%)和G190A(13.40%)次之,它们均可稳定存在并导致对NNRTIs的高度耐药。随治疗时间延长,以单一位点突变和突变型形式出现的NNRTIs耐药突变逐渐增加,导致高度耐药的可能性亦增加。 5. NRTIs单突变位点M41L、D67N、T215Y/F与K219Q/E/T相对稳定,可在体内稳定存在6个月以上。突变型M41L/L210LW/T215Y、M41L/E44DE/T215Y、M41L/E44D/T69D/V118I/L210W/T215Y、D67N/K70R/T215Y/K219E、L210W/T215Y都比较稳定。NNRTIs稳定的单位点突变为K103N、Y181C与G190A, 6. HIV-1耐药的发生与CD4、病毒载量具有高度相关性,即耐药发生时CD4下降、病毒载量明显上升。 第三部分新型HIV-1耐药相关突变位点的筛选 以往HIV-1耐药检测多数只针对药物的结合区,即只局限于蛋白酶与逆转录酶氨基酸密码子300位以前。最新的研究提示,酶结合以外区域的基因突变也有可能对耐药产生重要影响。在我国,多种因素导致可能存在未被认识的HIV-1耐药相关突变位点,且我国还没有针对RT区300位以外密码子耐药突变的研究。我们针对前期研究获得的接受和未接受抗病毒治疗的的971条HIV-1 pol基因序列(其中354条是包含300位密码子以外的RT全长序列),首先进行基因分型,然后分别与相应亚型的共享序列进行逐个密码子比对,筛选在接受与未接受抗病毒治疗的序列中存在显著差异的突变位点,然后再检索该突变位点在数据库中的收录情况,确定该位点是否可能为新型耐药相关突变位点。主要结果如下: 1.HIV-1 B′亚型治疗与未治疗人群序列中,蛋白酶抑制剂耐药相关突变的发生率无显著差异(F=0.875,P=0.5790.05),B′亚型与CRF01_AE亚型治疗人群中蛋白酶抑制剂耐药突变的发生率亦无显著性差异(F=0.058,P=0.5760.05),这与多数病人未使用蛋白酶抑制剂治疗有关; 2.HIV-1 B′亚型治疗与未治疗序列中,药物的使用与否对pol区基因序列的基因变异影响不大(F=0.003,P=0.7560.05),但药物存在加快了对耐药突变位点的选择(F=19.008,P=0.0070.05)。HIV-1 B′亚型与CRF_01AE亚型pol区基因序列突变发生没有显著差异(F=2.497,P=0.0570.05)。 3.HIV-1 B′亚型治疗序列中,21个逆转录酶抑制剂耐药相关突变位点的发生率显著高于未治疗序列(F=19.008,P=0.0070.05)。治疗序列中NRTIs的耐药突变模式以TAMs和M184V为主,分别为48.7%和12.1%,其次为Q151M突变复合体(5.77%);NNRTIs耐药突变以K103N和Y181C为主。 4.分析HIV-1 B′亚型治疗与未治疗序列中蛋白酶区密码子突变,通过与蛋白酶共享序列99个密码子逐一核对,发现2个突变(I13V和R57K)在两组序列中有差异,R57K在未治疗序列中出现的频率显著高于治疗序列,I13V则相反。这2个位点可能都是多态性突变位点。 5.将B′亚型共享序列与相应亚型治疗序列和未治疗序列逆转录酶全长560个密码子逐一比对,发现21个突变位点在两组人群中具有显著性差异,3个突变位点(I135V、S162C、V245E)的发生率在未治疗序列显著高于治疗序列,18个突变位点的发生率在治疗序列中显著高于未治疗序列,其中有14个是报道较少且与耐药相关性不明确的位点。 6.将初步筛选的14个突变位点逐个与美国斯坦福大学HIV耐药数据库中收录序列进行比较,确定L238I、K366R、T369V、A371V、I375V可能是与抗病毒治疗及耐药相关的突变。 7.逆转录酶区300位密码子以后可能与耐药相关的突变位点的发生率分别为:L238I为26.33%、K366R为21.74%、T369V为8.30%、A371V为7.51%、I375V为7.20%。 8.在我国以吸毒、性接触为主要感染途径的人群中,可能存在HIV-1毒株的新型重组模式,即CRF_BC重组毒株与B′亚型的二次重组。 9.HIV-1亚型分布与感染途径密切相关,以献/输血为主要感染途径的人群主要以B′亚型为主,而吸毒、性传播途径的人群亚型则较为丰富。HIV-1分布地域特征明显,在河南、河北、山东等地区地区以B′亚型为主,而在广西则以CRF01_AE为主。
[Abstract]:HIV resistance refers to the decline in drug susceptibility due to specific mutations in viral genes. A large number of studies have shown that there is a significant correlation between drug resistance and antiviral efficacy. Drug resistance is independently guided by factors such as plasma viral load, CD4 cell count and antiviral treatment history, etc. Factors contributing to the failure of antiretroviral therapy. Through a series of cross-sectional studies on AIDS patients in some provinces of China, this study clarified the occurrence and prevalence of HIV-1 drug-resistant strains at different time points after antiretroviral treatment; and 176 AIDS patients in a certain area of Henan Province were selected as subjects and analyzed through a five-year cohort study. The possible time of drug resistance, the pattern of drug resistance mutation and its evolution with time; the occurrence of new drug resistance mutation and the polymorphism of pol gene in the main epidemic strains under the unique treatment mode in China; and finally to understand the occurrence and epidemic regularity of drug-resistant HIV-1 strains in China, and to understand the drug-resistant HIV-1 strains. The molecular evolutionary characteristics of the virus strains enrich the knowledge of drug resistance-related mutations, and lay a foundation for accurate detection of drug-resistant strains and improving the efficacy of anti-HIV treatment.
Part one cross-sectional study on the prevalence of HIV-1 drug-resistant strains in some areas of China
From March 2004 to September 2008, cross-sectional studies were carried out on AIDS patients in Henan, Hebei, Shandong, Beijing, Guangdong, Gansu, Ningxia and Guangxi provinces and cities. Among them, 5 years of continuous surveillance in Henan, 3 years of continuous surveillance in Hebei, Shandong and Guangxi, 2 years of continuous surveillance in Beijing, Guangdong and Gansu, and 1 year of continuous surveillance in Ningxia. To analyze the effect of antiviral therapy, the target gene of Pol region was obtained by RT-PCR, and the sequence was submitted to Stanford University HIV resistance database to obtain drug resistance information.
1. Except Henan Province, the anti-HIV treatment in the monitoring province has achieved good results (the highest inhibition rate of the virus can reach 94.34%) and delayed the progress of AIDS.
2. drug-resistant strains occurred in many provinces, but showed a high prevalence in Henan (about 65%).
3. In Henan drug resistance surveillance population, drug compliance can only maintain about 75%, poor compliance is the direct cause of the high incidence of drug-resistant strains in this area;
4. The occurrence of drug resistance was highly correlated with the failure of antiviral treatment (OR = 0.942). Drug resistance was the key factor leading to the failure of antiviral treatment.
5. We should strengthen treatment supervision and antiviral treatment education, improve drug compliance, to delay the occurrence and epidemic of HIV-1 resistance, improve the success rate of treatment.
The second part is a cohort study on the occurrence and prevalence of HIV-1 drug-resistant strains in Henan province.
At present, China has carried out a number of cross-sectional studies on HIV resistance, but the cohort study is still rare in the world, and such research is very important to reveal the occurrence and development of drug resistance. By analyzing the sequence of drug resistance mutations at different time points, the pattern of drug resistance mutation occurrence and evolution, and the regularity of drug resistance mutation occurrence and development under the local special treatment mode, 173 AIDS patients were enrolled in the cohort, followed up 1 085 people, 6510 people a month, the most 10 times.
1. Drug compliance was maintained at about 75%. The median time of drug resistance to NRTIs was about 10 months after antiviral treatment in AIDS patients treated with AZT/DDI/NVP regimen. The peak of drug resistance was 6-12 months after treatment.
2. The median duration of NNRTIs resistance was 6.5 months after treatment, and the highest incidence of NNRTIs resistance mutation was 4-6 months after treatment.
3. The first NRTIs resistant mutation, 60% of which occurred in the early stage (within one year of treatment) was single site mutation, and increased in the form of mutation after one year. The later the single NRTIs mutation occurred, the greater the possibility of stability or development of mutation, the greater the contribution to drug resistance. The number of mutants leads to moderate to high drug resistance, and the probability of mutants leading to moderate to high drug resistance increases with the duration of treatment.
4. The NNRTIs resistance mutations in the form of single locus were most common in K103N (32.3%), followed by Y181C (14.20%) and G190A (13.40%). Both of them could be stable and lead to high resistance to NNRTIs. Increase.
5. NRTIs single mutation sites M41L, D67N, T215Y/F and K219Q/E/T are relatively stable, and can be stable in vivo for more than 6 months. Mutant M41L/L210LW/T215Y, M41L/E44DE/T215Y, M41L/E44D/T69D/V118I/L210W/T215Y, D67N/K70R/T215Y/K219E, L210W/T215Y are relatively stable. The mutant M41L/L210L210LW/T215Y, M41L/E44D/T69D/T69D/V118I/L210W/T215Y, and L210W/T215Y are stable.
6. The occurrence of HIV-1 resistance is highly correlated with CD4 and viral load, that is, CD4 decreases and viral load increases significantly when drug resistance occurs.
The third part is the screening of new HIV-1 resistance related mutation sites.
In the past, most HIV-1 drug resistance tests only focused on the drug-binding region, that is, only limited to the protease and reverse transcriptase amino acid codon before 300. Recent studies suggest that mutations in the region outside the enzyme-binding may also have an important impact on drug resistance. In our country, 971 HIV-1 pol gene sequences (354 of which are full-length RT sequences containing codons other than 300) received or not received antiviral therapy were studied. Genotyping was performed first, and then the corresponding subtypes were identified. After codon-by-codon alignment, the mutant sites with significant differences between those receiving antiviral treatment and those not receiving antiviral treatment were screened, and then the data of the mutant sites in the database were retrieved to determine whether the mutant site might be a novel drug resistance-related mutant.
1. There was no significant difference in the incidence of protease inhibitor resistance-related mutations between the HIV-1 B'subtype and untreated population (F = 0.875, P = 0.5790.05). There was no significant difference in the incidence of protease inhibitor resistance mutations between the HIV-1 B' subtype and CRF01_AE subtype (F = 0.058, P = 0.5760.05). Enzyme inhibitors are related to treatment.
2. In the treatment and untreated sequences of HIV-1 B'subtype, the use of drugs had little effect on gene mutation in Pol region (F = 0.003, P = 0.7560.05), but the presence of drugs accelerated the selection of resistant mutation sites (F = 19.008, P = 0.0070.05). There was no significant difference between HIV-1 B' subtype and CRF_01AE subtype in Pol region (F = 2.003, P = 0.7560.05). .497, P=0.0570.05).
3. In the treatment sequence of HIV-1 subtype B', the incidence of resistance-related mutations of 21 retroviral transcriptase inhibitors was significantly higher than that of untreated sequences (F = 19.008, P = 0.0070.05). In the treatment sequence, the resistance mutation patterns of NRTIs were mainly TAMs and M184V, 48.7% and 12.1% respectively, followed by Q151M mutation complex (5.77%). 181C is the main.
4. The mutation of protease codon in the untreated and untreated HIV-1 B'subtypes was analyzed. Two mutations (I13V and R57K) were found to be different in the two groups of sequences by checking 99 codons of the shared sequence with the protease. The frequency of R57K in untreated sequences was significantly higher than that in untreated sequences, whereas that of I13V was opposite. Polymorphic mutation sites.
5. By comparing the shared sequence of B'subtype with the treatment sequence and untreated sequence, we found that 21 mutation sites were significantly different between the two groups. The incidence of 3 mutation sites (I135V, S162C, V245E) in untreated sequence was significantly higher than that in untreated sequence, and 18 mutation sites occurred. The rate in the treatment sequence was significantly higher than that in the untreated sequence, 14 of which were less reported sites with unclear correlation with drug resistance.
6. Comparing the 14 mutation sites with the HIV drug resistance database of Stanford University, we found that L238I, K366R, T369V, A371V, I375V may be related to antiviral therapy and drug resistance.
7. The incidence of resistance-related mutations after 300 codons in the reverse transcriptase region were 26.33% in L238I, 21.74% in K366R, 8.30% in T369V, 7.51% in A371V and 7.20% in I375V, respectively.
8. There may be a new recombinant pattern of HIV-1 strain in the population with drug abuse and sexual contact as the main route of infection in China, that is, the recombinant strain of CRF_BC and the recombinant strain of B'.
9. The distribution of HIV-1 subtypes is closely related to the route of infection. The main route of infection is blood donation/transfusion, while drug abuse and sexual transmission are abundant. The distribution of HIV-1 subtypes is obvious in Henan, Hebei, Shandong and other regions, while CRF01_AE is dominant in Guangxi.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：博士
【学位授予年份】：2009
【分类号】：R181.3
本文编号：2251092
[Abstract]:HIV resistance refers to the decline in drug susceptibility due to specific mutations in viral genes. A large number of studies have shown that there is a significant correlation between drug resistance and antiviral efficacy. Drug resistance is independently guided by factors such as plasma viral load, CD4 cell count and antiviral treatment history, etc. Factors contributing to the failure of antiretroviral therapy. Through a series of cross-sectional studies on AIDS patients in some provinces of China, this study clarified the occurrence and prevalence of HIV-1 drug-resistant strains at different time points after antiretroviral treatment; and 176 AIDS patients in a certain area of Henan Province were selected as subjects and analyzed through a five-year cohort study. The possible time of drug resistance, the pattern of drug resistance mutation and its evolution with time; the occurrence of new drug resistance mutation and the polymorphism of pol gene in the main epidemic strains under the unique treatment mode in China; and finally to understand the occurrence and epidemic regularity of drug-resistant HIV-1 strains in China, and to understand the drug-resistant HIV-1 strains. The molecular evolutionary characteristics of the virus strains enrich the knowledge of drug resistance-related mutations, and lay a foundation for accurate detection of drug-resistant strains and improving the efficacy of anti-HIV treatment.
Part one cross-sectional study on the prevalence of HIV-1 drug-resistant strains in some areas of China
From March 2004 to September 2008, cross-sectional studies were carried out on AIDS patients in Henan, Hebei, Shandong, Beijing, Guangdong, Gansu, Ningxia and Guangxi provinces and cities. Among them, 5 years of continuous surveillance in Henan, 3 years of continuous surveillance in Hebei, Shandong and Guangxi, 2 years of continuous surveillance in Beijing, Guangdong and Gansu, and 1 year of continuous surveillance in Ningxia. To analyze the effect of antiviral therapy, the target gene of Pol region was obtained by RT-PCR, and the sequence was submitted to Stanford University HIV resistance database to obtain drug resistance information.
1. Except Henan Province, the anti-HIV treatment in the monitoring province has achieved good results (the highest inhibition rate of the virus can reach 94.34%) and delayed the progress of AIDS.
2. drug-resistant strains occurred in many provinces, but showed a high prevalence in Henan (about 65%).
3. In Henan drug resistance surveillance population, drug compliance can only maintain about 75%, poor compliance is the direct cause of the high incidence of drug-resistant strains in this area;
4. The occurrence of drug resistance was highly correlated with the failure of antiviral treatment (OR = 0.942). Drug resistance was the key factor leading to the failure of antiviral treatment.
5. We should strengthen treatment supervision and antiviral treatment education, improve drug compliance, to delay the occurrence and epidemic of HIV-1 resistance, improve the success rate of treatment.
The second part is a cohort study on the occurrence and prevalence of HIV-1 drug-resistant strains in Henan province.
At present, China has carried out a number of cross-sectional studies on HIV resistance, but the cohort study is still rare in the world, and such research is very important to reveal the occurrence and development of drug resistance. By analyzing the sequence of drug resistance mutations at different time points, the pattern of drug resistance mutation occurrence and evolution, and the regularity of drug resistance mutation occurrence and development under the local special treatment mode, 173 AIDS patients were enrolled in the cohort, followed up 1 085 people, 6510 people a month, the most 10 times.
1. Drug compliance was maintained at about 75%. The median time of drug resistance to NRTIs was about 10 months after antiviral treatment in AIDS patients treated with AZT/DDI/NVP regimen. The peak of drug resistance was 6-12 months after treatment.
2. The median duration of NNRTIs resistance was 6.5 months after treatment, and the highest incidence of NNRTIs resistance mutation was 4-6 months after treatment.
3. The first NRTIs resistant mutation, 60% of which occurred in the early stage (within one year of treatment) was single site mutation, and increased in the form of mutation after one year. The later the single NRTIs mutation occurred, the greater the possibility of stability or development of mutation, the greater the contribution to drug resistance. The number of mutants leads to moderate to high drug resistance, and the probability of mutants leading to moderate to high drug resistance increases with the duration of treatment.
4. The NNRTIs resistance mutations in the form of single locus were most common in K103N (32.3%), followed by Y181C (14.20%) and G190A (13.40%). Both of them could be stable and lead to high resistance to NNRTIs. Increase.
5. NRTIs single mutation sites M41L, D67N, T215Y/F and K219Q/E/T are relatively stable, and can be stable in vivo for more than 6 months. Mutant M41L/L210LW/T215Y, M41L/E44DE/T215Y, M41L/E44D/T69D/V118I/L210W/T215Y, D67N/K70R/T215Y/K219E, L210W/T215Y are relatively stable. The mutant M41L/L210L210LW/T215Y, M41L/E44D/T69D/T69D/V118I/L210W/T215Y, and L210W/T215Y are stable.
6. The occurrence of HIV-1 resistance is highly correlated with CD4 and viral load, that is, CD4 decreases and viral load increases significantly when drug resistance occurs.
The third part is the screening of new HIV-1 resistance related mutation sites.
In the past, most HIV-1 drug resistance tests only focused on the drug-binding region, that is, only limited to the protease and reverse transcriptase amino acid codon before 300. Recent studies suggest that mutations in the region outside the enzyme-binding may also have an important impact on drug resistance. In our country, 971 HIV-1 pol gene sequences (354 of which are full-length RT sequences containing codons other than 300) received or not received antiviral therapy were studied. Genotyping was performed first, and then the corresponding subtypes were identified. After codon-by-codon alignment, the mutant sites with significant differences between those receiving antiviral treatment and those not receiving antiviral treatment were screened, and then the data of the mutant sites in the database were retrieved to determine whether the mutant site might be a novel drug resistance-related mutant.
1. There was no significant difference in the incidence of protease inhibitor resistance-related mutations between the HIV-1 B'subtype and untreated population (F = 0.875, P = 0.5790.05). There was no significant difference in the incidence of protease inhibitor resistance mutations between the HIV-1 B' subtype and CRF01_AE subtype (F = 0.058, P = 0.5760.05). Enzyme inhibitors are related to treatment.
2. In the treatment and untreated sequences of HIV-1 B'subtype, the use of drugs had little effect on gene mutation in Pol region (F = 0.003, P = 0.7560.05), but the presence of drugs accelerated the selection of resistant mutation sites (F = 19.008, P = 0.0070.05). There was no significant difference between HIV-1 B' subtype and CRF_01AE subtype in Pol region (F = 2.003, P = 0.7560.05). .497, P=0.0570.05).
3. In the treatment sequence of HIV-1 subtype B', the incidence of resistance-related mutations of 21 retroviral transcriptase inhibitors was significantly higher than that of untreated sequences (F = 19.008, P = 0.0070.05). In the treatment sequence, the resistance mutation patterns of NRTIs were mainly TAMs and M184V, 48.7% and 12.1% respectively, followed by Q151M mutation complex (5.77%). 181C is the main.
4. The mutation of protease codon in the untreated and untreated HIV-1 B'subtypes was analyzed. Two mutations (I13V and R57K) were found to be different in the two groups of sequences by checking 99 codons of the shared sequence with the protease. The frequency of R57K in untreated sequences was significantly higher than that in untreated sequences, whereas that of I13V was opposite. Polymorphic mutation sites.
5. By comparing the shared sequence of B'subtype with the treatment sequence and untreated sequence, we found that 21 mutation sites were significantly different between the two groups. The incidence of 3 mutation sites (I135V, S162C, V245E) in untreated sequence was significantly higher than that in untreated sequence, and 18 mutation sites occurred. The rate in the treatment sequence was significantly higher than that in the untreated sequence, 14 of which were less reported sites with unclear correlation with drug resistance.
6. Comparing the 14 mutation sites with the HIV drug resistance database of Stanford University, we found that L238I, K366R, T369V, A371V, I375V may be related to antiviral therapy and drug resistance.
7. The incidence of resistance-related mutations after 300 codons in the reverse transcriptase region were 26.33% in L238I, 21.74% in K366R, 8.30% in T369V, 7.51% in A371V and 7.20% in I375V, respectively.
8. There may be a new recombinant pattern of HIV-1 strain in the population with drug abuse and sexual contact as the main route of infection in China, that is, the recombinant strain of CRF_BC and the recombinant strain of B'.
9. The distribution of HIV-1 subtypes is closely related to the route of infection. The main route of infection is blood donation/transfusion, while drug abuse and sexual transmission are abundant. The distribution of HIV-1 subtypes is obvious in Henan, Hebei, Shandong and other regions, while CRF01_AE is dominant in Guangxi.
【学位授予单位】：中国人民解放军军事医学科学院
【学位级别】：博士
【学位授予年份】：2009
【分类号】：R181.3
【引证文献】
相关期刊论文 前2条
1 吴守丽;严延生;;HIV耐药性及耐药检测研究进展[J];中国病毒病杂志;2012年02期
2 邹雯;刘颖;王健;高国建;董继鹏;咸庆飞;;HIV耐药的研究现状[J];中国中药杂志;2013年15期
相关硕士学位论文 前2条
1 宋丹;郑州地区男男同性恋人群HIV-1感染者基因亚型及耐药分析[D];郑州大学;2012年
2 邱丽君;福建省HIV-1耐药性检测及新耐药相关突变位点的研究[D];福建医科大学;2013年
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