(3.238.130.97) 您好!臺灣時間:2021/05/10 12:48
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:楊宗諭
研究生(外文):Zong-Yu Yang
論文名稱:以次世代定序評估台灣人類免疫缺乏病毒基因型之抗藥性與偵測接受過治療病患體內之多重感染
論文名稱(外文):Evaluation of deep sequencing in determination of genotypic resistance and detection of multiple HIV infections in treatment-experienced HIV-infected patients in Taiwan
指導教授:張淑媛張淑媛引用關係
指導教授(外文):Sui-Yuan Chang
口試委員:高全良李君男洪健清
口試日期:2013-07-15
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:醫學檢驗暨生物技術學研究所
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:中文
論文頁數:103
中文關鍵詞:多重感染次世代定序系統抗藥性
外文關鍵詞:super-infectionnext-generation sequencingdrug resistance
相關次數:
  • 被引用被引用:0
  • 點閱點閱:145
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
在台灣的HIV-1感染者以男同性戀者為主,感染之病毒亞型主要為B亞型;靜脈注射毒癮者次之,感染之病毒亞型以CRF07_BC為主;而異性戀者感染之病毒亞型有B亞型、CRF07_BC和CRF01_AE。由於有多種病毒亞型在台灣同時流行,感染者體內存在不同之病毒株或多重感染的機會也相對提高。過去由於技術上的限制,當HIV-1感染者體內存在兩種或以上病毒時,很難以傳統桑格氏定序偵測。本研究期以具更高敏感性之次世代定序系統,來了解台灣是否有多重感染發生及其在抗藥性基因型檢測的應用性。
本研究首先評估次世代定序系統之引子在不同亞型與不同循環重組模式中是否適用,再評估引子在台大醫院HIV抗藥性篩檢資料庫中不同亞型是否適用,最後以臨床病人檢體進行實際測試。當病人之HIV蛋白酶和反轉錄酶區域的桑格氏定序結果,分別被定義為不同的基因型,便被認為可能是共感染或多重感染或經過重組。我們提供三位疑似多重感染患者與九名其餘亞型之患者,並使用羅氏454次世代定序系統調查他們是否是共感染或多重感染,接著在針對一多重感染患者做長達6年之回溯性研究。
結果顯示次世代系統引子對於全球部份亞型及CRF可能不適用,而對台灣的B亞型與CRF07_BC適用,對CRF01_AE有較差適用性。不論是否懷疑為多重感染,部份HIV病患確實同時感染不只一種的HIV亞型。因為共同感染,一些重組病毒株確實存在於部分檢體中,證實重組確實會發生在這些感染了不同病毒株的病人體中。有部份檢體之次族群被分析出具有與主要族群不同之抗藥性變化。而在長時間的回溯性研究,可以看到病人體內不同亞型族群的改變,重組病毒株的消長,及抗藥性族群的出現與置換。本研究顯示此次世代系統適用於台灣不同亞型之抗藥性檢測與多重感染之偵測,而台灣多重感染的發生率可能被低估,需要進一步評估。


In Taiwan, the major transmisstion routes for HIV infection are men who have sex with men (MSM), injecting drug use (IDU), and hetersexual sexual contact. The major HIV subtypes in these three populations are subtype B, CRF07_BC, and subtypeB/CRF07_BC/CRF01_AE, respectively. The cocirculation of different subtypes in Taiwan has raised the concern of super-infection or co-infection by different HIV subtypes.
In the past, due to the technical limitations of Sanger sequencing, co-infection or super-infection patients were difficult to be identified. Here we used the deep sequencing to investigate the presence of super-infection or co-infection in Taiwan and to evaluate its application in the genotypic drug resistance testing.
First, we evaluated the applicability of next generation sequencing (NGS) primers in different subtypes from the database and the epidemic strains amplified in Taiwan. We selected three patients whose protease and reverse transcriptase sequences were previously defined as different genotypes to evaluate whether they were infected by different HIV subtypes. Nine patients infected with dominant HIV-1 subtypes in Taiwan were selected for comparison. We used Roche 454 NGS to investigate whether these patients had super-infection, and we determined the genotypic resistance of a patient with super-infection in a longitudinal follow-up study.
Our data showed that the primers designed for NGS might not be suitable for all HIV subtypes. Super-infection (or co-infection) was observed in some cases. Because of multiple infections with HIV, recombinant strains did exist. Some undetected drug resistance mutants appeared in a minor viral population. In the longitudinal study, we observed the shift of different virus population, the rise and fall of recombinant strains, and the replacement of wild type by resistance strains.
In conclusion, the NGS can be applied to detect the genetypic drug resistance and super-infection. Furthermore, the rate of super-infection in Taiwan may have been underestimated.


目錄
致謝 VIII
中文摘要 IX
英文摘要 X
第一章 前言 1
1-1人類免疫缺乏病毒 1
1-1-1病毒簡介 1
1-1-2 一般病毒亞型與循環重組形式 1
1-1-3 病毒傳染模式與危險族群 2
1-1-4 台灣HIV感染歷史與現況 2
1-2高效率抗反轉錄病毒藥物治療 3
1-2-1 高效率抗反轉錄病毒治療藥物簡介 3
1-2-2 核苷酸類反轉錄酶抑制劑(NRTI) 3
1-2-3 非核苷酸反轉錄酶抑制劑(NNRTI) 4
1-2-4 蛋白酶抑制劑(PI) 4
1-2-5 其餘抗反轉錄病毒藥物 4
1-2-6 治療指引 5
1-2-7 抗藥性基因突變介紹 5
1-3 共感染或多重感染人類免疫缺乏病毒 6
1-3-1 共感染或多重感染HIV簡介 6
1-3-2 共感染或多重感染之結果 6
1-3-3 共感染或多重感染之偵測 7
1-4 次世代定序系統 8
1-4-1 定序系統之發展 8
1-4-2 次世代定序系統之簡介 8
1-4-3 次世代定序系統在HIV的應用 10
第二章 實驗動機與目的 12
第三章 實驗方法與材料 13
3-1 實驗材料 13
3-1-1 檢體 13
3-1-2 試劑 13
3-1-3 特殊實驗用具 13
3-1-4 實驗儀器 13
3-2 實驗方法 14
3-2-1 病毒RNA抽取 14
3-2-2 病毒RNA反轉錄反應 14
3-2-3 擴增子生成反應 15
3-2-4 擴增子的純化 16
3-2-5 以Picogreen螢光染料定量DNA濃度 16
3-2-6 委託羅氏藥廠進行最終反應 17
3-2-7 統計方法與分析軟體 18
第四章 實驗結果 21
4-1 引子的適用性分析 21
4-2 檢體的挑選 22
4-3 檢體前處理之結果 22
4-4 懷疑為多重感染之檢體分析結果 23
4-5 B亞型之檢體分析結果 25
4-6 CRF01_AE之檢體分析結果 26
4-7 CRF07_BC之檢體分析結果 27
4-8 CRF07_BC之重複檢體分析結果 29
4-9 單一檢體之回溯性研究 29
第五章 實驗討論 32
第六章 參考文獻 38


圖目錄

圖一、 次世代定序系統檢體編號1-1之(A)第一片段(RTP-I)與(B)第二片段(RTP-II) 50
圖二、 次世代定序系統檢體編號1-1之(A)第三片段(RTP-III)與(B)第四片段(RTP-IV) 51
圖三、 次世代定序系統檢體編號1-3之(A)第一片段(RTP-I)與(B)第二片段(RTP-II) 52
圖四、 次世代定序系統檢體編號1-3之(A)第三片段(RTP-III)與(B)第四片段(RTP-IV)與(C)第四片段中的CRF01_AE 53
圖五、 次世代定序系統檢體編號3之第三與第四片段重疊序列比較 54
圖六、 次世代定序系統檢體編號1-10之(A)第一片段(RTP-I)與(B)第二片段(RTP-II)與(C)第三片段(RTP-III)與(D)第四片段(RTP-IV) 55
圖七、 次世代定序系統檢體編號1-6之(A)第一片段(RTP-I)與(B)第三片段(RTP-III)與(C)第四片段(RTP-IV) 56
圖八、 次世代定序系統檢體編號1-9之(A)第一片段(RTP-I)與(B)第三片段(RTP-III)與(C)第四片段(RTP-IV) 57
圖九、 次世代定序系統檢體編號2-1之(A)第一片段(RTP-I)與(B)第一片段(RTP-II) 58
圖十、 次世代定序系統檢體編號1-4之(A)第一片段(RTP-I)與(B)第二片段(RTP-II)與(C)第三片段(RTP-III)與(D)第四片段(RTP-IV) 59
圖十一、 次世代定序系統檢體編號1-5之(A)第一片段(RTP-I)與(B)第二片段(RTP-II)與(C)第三片段(RTP-III)與(D)第四片段(RTP-IV) 60
圖十二、 次世代定序系統檢體編號1-2之(A)第一片段(RTP-I)與(B)第三片段(RTP-III)與(C)第四片段(RTP-IV) 61
圖十三、 次世代定序系統檢體編號1-7之(A)第一片段(RTP-I)與(B)第二片段(RTP-II)與(C)第三片段(RTP-III)與(D)第四片段(RTP-IV) 62
圖十四、 次世代定序系統檢體編號1-8之(A)第一片段(RTP-I)與(B)第二片段(RTP-II)與(C)第四片段(RTP-IV) 63
圖十五、 次世代定序系統檢體編號2-5之(A)第一片段(RTP-I)與(B)第二片段(RTP-II) 64
圖十六、 次世代定序系統檢體編號2-6之(A)第一片段(RTP-I)與(B)第二片段(RTP-II) 65
圖十七、 次世代定序系統檢體編號2-6之(C)第三片段(RTP-III)與(D)第四片段(RTP-IV) 66
圖十八、 次世代定序系統檢體編號2-7之(A)第一片段(RTP-I)與(B)第二片段(RTP-II)與(C)第三片段(RTP-III)與(D)第四片段(RTP-IV) 67
圖十九、 次世代定序系統檢體編號2-8之(A)第一片段(RTP-I)與(B)第二片段(RTP-II) 68
圖二十、 次世代定序系統檢體編號2-8之(A)第三片段(RTP-III)與(B)第四片段(RTP-IV) 69
圖二十一、 次世代定序系統檢體編號2-9之(A)第三片段(RTP-III)與(B)第四片段(RTP-IV) 70
圖二十二、 次世代定序系統檢體編號2-10之(A)第三片段(RTP-III)與(B)第四片段(RTP-IV) 71
圖二十三、 次世代定序系統檢體編號1-7與2-2之重複檢體第一片段比較 72
圖二十四、 次世代定序系統檢體編號1-7與2-2之重複檢體第二片段比較 73
圖二十五、 次世代定序系統檢體編號1-7與2-2之重複檢體第三片段比較 74
圖二十六、 次世代定序系統檢體編號1-7與2-2之重複檢體第四片段比較 75
圖二十七、 次世代定序系統檢體編號2-3之第二片段(RTP-II) 76
圖二十八、 次世代定序系統檢體編號1-8與2-4之重複檢體第一片段比較 77
圖二十九、 次世代定序系統檢體編號1-8與2-4之重複檢體第二片段比較 78
圖三十、 檢體1-7號之病毒量、CD4細胞數與用藥資訊,以及檢體時間點相關性 79
圖三十一、 長時間回溯性實驗第一片段之病毒族群分布 80
圖三十二、 長時間回溯性實驗第一片段之重組分析 81
圖三十三、 長時間回溯性實驗第二片段之病毒族群分布 82
圖三十四、 長時間回溯性實驗第三片段之病毒族群分布 83
圖三十五、 長時間回溯性實驗第四片段之病毒族群分布 84
圖三十六、 長時間回溯性實驗體內之亞型分布 85


表目錄

表一、黑色螢光盤之檢體對應孔 86
表二、主要類別之高效率反轉錄病毒藥物 87
表三、其餘類別之高效率反轉錄病毒藥物 88
表四、次世代定序系統擴增子生成盤引子序列 89
表五、HIV病患之數目與其基因型分布表 90
表六、所有基因型與引子結合位之差異:第一片段 91
表七、所有基因型與引子結合位之差異:第二片段 92
表八、所有基因型與引子結合位之差異:第三片段 93
表九、所有基因型與引子結合位之差異:第四片段 94
表十、次世代定序系統引子與台大醫院不同HIV亞型之引子結合位比較:第一片段 95
表十一、次世代定序系統引子與台大醫院不同HIV亞型之引子結合位比較:第二片段 96
表十二、次世代定序系統引子與台大醫院不同HIV亞型之引子結合位比較:第三片段 97
表十三、次世代定序系統引子與台大醫院不同HIV亞型之引子結合位比較:第四片段 98
表十四、第一片段不同HIV亞型之引子結合位差異分佈 99
表十五、第二片段不同HIV亞型之引子結合位差異分佈 100
表十六、第三片段不同HIV亞型之引子結合位差異分佈 101
表十七、第四片段不同HIV亞型之引子結合位差異分佈 102
表十八、次世代定序系統之檢體清單 103






1.Robertson, D.L., J.P. Anderson, J.A. Bradac, et al., HIV-1 nomenclature proposal. Science, 2000. 288(5463): p. 55-6.
2.Linke, U., AIDS in Africa. Science, 1986. 231(4735): p. 203.
3.Arien, K.K., G. Vanham, and E.J. Arts, Is HIV-1 evolving to a less virulent form in humans? Nat Rev Microbiol, 2007. 5(2): p. 141-51.
4.Lin, K.T., S.H. Huang, C.L. Kao, et al., An autopsy-proved case of AIDS in Taiwan. Asian Pac J Allergy Immunol, 1987. 5(1): p. 25-31.
5.Chen, Y.M., C.M. Lee, R.Y. Lin, and H.J. Chang, Molecular epidemiology and trends of HIV-1 subtypes in Taiwan. J Acquir Immune Defic Syndr Hum Retrovirol, 1998. 19(4): p. 393-402.
6.Chen, Y.M., Y.C. Lan, S.F. Lai, et al., HIV-1 CRF07_BC infections, injecting drug users, Taiwan. Emerg Infect Dis, 2006. 12(4): p. 703-5.
7.Chen, Y.M. and S.H. Kuo, HIV-1 in Taiwan. Lancet, 2007. 369(9562): p. 623-5.
8.Yang, C.H., S.Y. Yang, M.H. Shen, and H.S. Kuo, The changing epidemiology of prevalent diagnosed HIV infections in Taiwan, 1984-2005. Int J Drug Policy, 2008. 19(4): p. 317-23.
9.Huang, Y.F., H.S. Kuo, C.Y. Lew-Ting, et al., Mortality among a cohort of drug users after their release from prison: an evaluation of the effectiveness of a harm reduction program in Taiwan. Addiction. 106(8): p. 1437-45.
10.Darbyshire, J., Perspectives in drug therapy of HIV infection. Drugs, 1995. 49 Suppl 1: p. 1-3; discussion 38-40.
11.Mansky, L.M., Retrovirus mutation rates and their role in genetic variation. Journal of General Virology, 1998. 79: p. 1337-1345.
12.Rambaut, A., D. Posada, K.A. Crandall, and E.C. Holmes, The causes and consequences of HIV evolution. Nat Rev Genet, 2004. 5(1): p. 52-61.
13.Ho, D.D., Time to hit HIV, early and hard. N Engl J Med, 1995. 333(7): p. 450-1.
14.Guidelines for using antiretroviral agents among HIV-infected adults and adolescents : recommendations of the panel on clinical practices for treatment of HIV. Morbidity and mortality weekly report, recommendations and report vol. 51, no. RR-7. 2002, [Atlanta, GA]
[Washington, D.C.]: Epidemiology Program Office, Center for Disease Control and Prevention U.S. Government Printing Office, Superintendent of Documents. 56 p.
15.Patick, A.K. and K.E. Potts, Protease inhibitors as antiviral agents. Clinical Microbiology Reviews, 1998. 11(4): p. 614-+.
16.Pneumocystis pneumonia--Los Angeles. MMWR Morb Mortal Wkly Rep, 1981. 30(21): p. 250-2.
17.Fultz, P.N., A. Srinivasan, C.R. Greene, et al., Superinfection of a chimpanzee with a second strain of human immunodeficiency virus. J Virol, 1987. 61(12): p. 4026-9.
18.Angel, J.B., Y.W. Hu, S. Kravcik, et al., Virological evaluation of the ''Ottawa case'' indicates no evidence for HIV-1 superinfection. AIDS, 2004. 18(2): p. 331-4.
19.Jost, S., M.C. Bernard, L. Kaiser, et al., A patient with HIV-1 superinfection. N Engl J Med, 2002. 347(10): p. 731-6.
20.Ramos, A., D.J. Hu, L. Nguyen, et al., Intersubtype human immunodeficiency virus type 1 superinfection following seroconversion to primary infection in two injection drug users. J Virol, 2002. 76(15): p. 7444-52.
21.Altfeld, M., T.M. Allen, X.G. Yu, et al., HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus. Nature, 2002. 420(6914): p. 434-9.
22.Blackard, J.T., D.E. Cohen, and K.H. Mayer, Human immunodeficiency virus superinfection and recombination: current state of knowledge and potential clinical consequences. Clin Infect Dis, 2002. 34(8): p. 1108-14.
23.Hemelaar, J., E. Gouws, P.D. Ghys, S. Osmanov, and W.-U.N.H.I. C, Global trends in molecular epidemiology of HIV-1 during 2000-2007. AIDS, 2011. 25(5): p. 679-689.
24.Smith, D.M., J.K. Wong, G.K. Hightower, et al., HIV drug resistance acquired through superinfection. AIDS, 2005. 19(12): p. 1251-1256.
25.Ssemwanga, D., F. Lyagoba, N. Ndembi, et al., Multiple HIV-1 infections with evidence of recombination in heterosexual partnerships in a low risk Rural Clinical Cohort in Uganda. Virology. 411(1): p. 113-31.
26.Morrison, C.S., P.L. Chen, I. Nankya, et al., Hormonal contraceptive use and HIV disease progression among women in Uganda and Zimbabwe. J Acquir Immune Defic Syndr. 57(2): p. 157-64.
27.Rangsin, R., P. Piyaraj, T. Sirisanthana, et al., The natural history of HIV-1 subtype E infection in young men in Thailand with up to 14 years of follow-up. AIDS, 2007. 21 Suppl 6: p. S39-46.
28.Todd, J., J.R. Glynn, M. Marston, et al., Time from HIV seroconversion to death: a collaborative analysis of eight studies in six low and middle-income countries before highly active antiretroviral therapy. AIDS, 2007. 21 Suppl 6: p. S55-63.
29.Gottlieb, G.S., D.C. Nickle, M.A. Jensen, et al., Dual HIV-1 infection associated with rapid disease progression. Lancet, 2004. 363(9409): p. 619-22.
30.Clerc, O., S. Colombo, S. Yerly, A. Telenti, and M. Cavassini, HIV-1 elite controllers: beware of super-infections. J Clin Virol. 47(4): p. 376-8.
31.Rachinger, A., T.D. van de Ven, J.A. Burger, H. Schuitemaker, and A.B. van''t Wout, Evaluation of pre-screening methods for the identification of HIV-1 superinfection. Journal of Virological Methods, 2010. 165(2): p. 311-317.
32.Piantadosi, A., M.O. Ngayo, B. Chohan, and J. Overbaugh, Examination of a second region of the HIV type 1 genome reveals additional cases of superinfection. Aids Research and Human Retroviruses, 2008. 24(9): p. 1221-1224.
33.Sanger, F., S. Nicklen, and A.R. Coulson, DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A, 1977. 74(12): p. 5463-7.
34.Heiger, D.N., A.S. Cohen, and B.L. Karger, Separation of DNA restriction fragments by high performance capillary electrophoresis with low and zero crosslinked polyacrylamide using continuous and pulsed electric fields. J Chromatogr, 1990. 516(1): p. 33-48.
35.Pfeifer, G.P., S.D. Steigerwald, P.R. Mueller, B. Wold, and A.D. Riggs, Genomic sequencing and methylation analysis by ligation mediated PCR. Science, 1989. 246(4931): p. 810-3.
36.Drmanac, R., I. Labat, I. Brukner, and R. Crkvenjakov, Sequencing of megabase plus DNA by hybridization: theory of the method. Genomics, 1989. 4(2): p. 114-28.
37.Hyman, E.D., A new method of sequencing DNA. Anal Biochem, 1988. 174(2): p. 423-36.
38.Ahmadian, A., M. Ehn, and S. Hober, Pyrosequencing: history, biochemistry and future. Clin Chim Acta, 2006. 363(1-2): p. 83-94.
39.Tucker, T., M. Marra, and J.M. Friedman, Massively parallel sequencing: the next big thing in genetic medicine. Am J Hum Genet, 2009. 85(2): p. 142-54.
40.Holt, R.A. and S.J. Jones, The new paradigm of flow cell sequencing. Genome Res, 2008. 18(6): p. 839-46.
41.Bentley, D.R., Whole-genome re-sequencing. Curr Opin Genet Dev, 2006. 16(6): p. 545-52.
42.Robertson, D.L., B.H. Hahn, and P.M. Sharp, Recombination in AIDS viruses. J Mol Evol, 1995. 40(3): p. 249-59.
43.Perelson, A.S. and R.M. Ribeiro, Estimating drug efficacy and viral dynamic parameters: HIV and HCV. Stat Med, 2008. 27(23): p. 4647-57.
44.Wang, C., Y. Mitsuya, B. Gharizadeh, M. Ronaghi, and R.W. Shafer, Characterization of mutation spectra with ultra-deep pyrosequencing: application to HIV-1 drug resistance. Genome Res, 2007. 17(8): p. 1195-201.
45.Alteri, C., M.M. Santoro, I. Abbate, et al., ''Sentinel'' mutations in standard population sequencing can predict the presence of HIV-1 reverse transcriptase major mutations detectable only by ultra-deep pyrosequencing. Journal of Antimicrobial Chemotherapy, 2011. 66(11): p. 2615-2623.
46.Messiaen, P., C. Verhofstede, I. Vandenbroucke, et al., Ultra-Deep Sequencing of HIV-1 Reverse Transcriptase Before Start of an NNRTI-based Regimen in Treatment-naive Patients. Virology, 2012. 426(1): p. 7-11.
47.Mukherjee, R., S.T. Jensen, F. Male, et al., Switching between raltegravir resistance pathways analyzed by deep sequencing. AIDS, 2011. 25(16): p. 1951-1959.
48.Swenson, L.C., A. Moores, A.J. Low, et al., Improved detection of CXCR4-using HIV by V3 genotyping: application of population-based and "deep" sequencing to plasma RNA and proviral DNA. J Acquir Immune Defic Syndr. 54(5): p. 506-10.
49.Swenson, L.C., T. Mo, W.W. Dong, et al., Deep sequencing to infer HIV-1 co-receptor usage: application to three clinical trials of maraviroc in treatment-experienced patients. J Infect Dis. 203(2): p. 237-45.
50.Poon, A.F.Y., R.A. McGovern, T. Mo, et al., Dates of HIV infection can be estimated for seroprevalent patients by coalescent analysis of serial next-generation sequencing data. AIDS, 2011. 25(16): p. 2019-2026.
51.Tsibris, A.M., B. Korber, R. Arnaout, et al., Quantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivo. PLoS One, 2009. 4(5): p. e5683.
52.Fischer, W., V.V. Ganusov, E.E. Giorgi, et al., Transmission of single HIV-1 genomes and dynamics of early immune escape revealed by ultra-deep sequencing. PLoS One. 5(8): p. e12303.
53.Redd, A.D., A. Collinson-Streng, C. Martens, et al., Identification of HIV Superinfection in Seroconcordant Couples in Rakai, Uganda, by Use of Next-Generation Deep Sequencing. Journal of Clinical Microbiology, 2011. 49(8): p. 2859-2867.
54.MacArthur, M., Viral sex: The nature of AIDS - Goudsmit,J. Library Journal, 1997. 122(7): p. 112-112.
55.Rachinger, A., P. Manyenga, J.A. Burger, et al., Low incidence of HIV-1 superinfection even after episodes of unsafe sexual behavior of homosexual men in the Amsterdam Cohort Studies on HIV Infection and AIDS. J Infect Dis. 203(11): p. 1621-8.
56.Tsui, R., B.L. Herring, J.D. Barbour, et al., Human immunodeficiency virus type 1 superinfection was not detected following 215 years of injection drug user exposure. J Virol, 2004. 78(1): p. 94-103.
57.Gonzales, M.J., E. Delwart, S.Y. Rhee, et al., Lack of detectable human immunodeficiency virus type 1 superinfection during 1072 person-years of observation. J Infect Dis, 2003. 188(3): p. 397-405.
58.Soares de Oliveira, A.C., R. Pessoa de Farias, A.C. da Costa, et al., Frequency of subtype B and F1 dual infection in HIV-1 positive, Brazilian men who have sex with men. Virol J. 9: p. 223.
59.Templeton, A.R., M.G. Kramer, J. Jarvis, et al., Multiple-infection and recombination in HIV-1 within a longitudinal cohort of women. Retrovirology, 2009. 6.
60.van der Kuyl, A.C., K. Kozaczynska, R. van den Burg, et al., Triple HIV-1 infection. New England Journal of Medicine, 2005. 352(24): p. 2557-2559.
61.Yang, O.O., E.S. Daar, B.D. Jamieson, et al., Human immunodeficiency virus type 1 clade B superinfection: Evidence for differential immune containment of distinct clade B strains. Journal of Virology, 2005. 79(2): p. 860-868.
62.Jost, S., M.C. Bernard, L. Kaiser, et al., A patient with HIV-1 superinfection. New England Journal of Medicine, 2002. 347(10): p. 731-736.
63.Pernas, M., C. Casado, R. Fuentes, M.J. Perez-Elias, and C. Lopez-Galindez, A dual superinfection and recombination within HIV-1 subtype B 12 years after primoinfection. Jaids-Journal of Acquired Immune Deficiency Syndromes, 2006. 42(1): p. 12-18.
64.Smith, D.M., M.C. Strain, S.D.W. Frost, et al., Lack of neutralizing antibody response to HIV-1 predisposes to superinfection. Virology, 2006. 355(1): p. 1-5.
65.Kao, C.F., S.Y. Chang, K.T. Hsia, et al., Surveillance of HIV type 1 recent infection and molecular epidemiology among different risk behaviors between 2007 and 2009 after the HIV type 1 CRF07_BC outbreak in Taiwan. AIDS Res Hum Retroviruses. 27(7): p. 745-9.
66.Kanki, P.J., D.J. Hamel, J.L. Sankale, et al., Human immunodeficiency virus type 1 subtypes differ in disease progression. Journal of Infectious Diseases, 1999. 179(1): p. 68-73.
67.Mori, M., B. Sriwanthana, N. Wichukchinda, et al., Unique CRF01_AE Gag CTL epitopes associated with lower HIV-viral load and delayed disease progression in a cohort of HIV-infected Thais. PLoS One. 6(8): p. e22680.
68.Liu, S.L., J.E. Mittler, D.C. Nickle, et al., Selection for human immunodeficiency virus type 1 recombinants in a patient with rapid progression to AIDS. J Virol, 2002. 76(21): p. 10674-84.
69.Brehm, J.H., D. Koontz, J.D. Meteer, et al., Selection of mutations in the connection and RNase H domains of human immunodeficiency virus type 1 reverse transcriptase that increase resistance to 3''-azido-3''-dideoxythymidine. J Virol, 2007. 81(15): p. 7852-9.
70.Phillips, R.E., S. Rowlandjones, D.F. Nixon, et al., Human-Immunodeficiency-Virus Genetic-Variation That Can Escape Cytotoxic T-Cell Recognition. Nature, 1991. 354(6353): p. 453-459.
71.Klein, M.R., C.A. Vanbaalen, A.M. Holwerda, et al., Kinetics of Gag-Specific Cytotoxic T-Lymphocyte Responses during the Clinical Course of Hiv-1 Infection - a Longitudinal Analysis of Rapid Progressors and Long-Term Asymptomatics. Journal of Experimental Medicine, 1995. 181(4): p. 1365-1372.
72.Mellors, J.W., A. Munoz, J.V. Giorgi, et al., Plasma viral load and CD4(+) lymphocytes as prognostic markers of HIV-1 infection. Annals of Internal Medicine, 1997. 126(12): p. 946-954.
73.Saracco, A., M. Musicco, A. Nicolosi, et al., Man-to-woman sexual transmission of HIV: longitudinal study of 343 steady partners of infected men. J Acquir Immune Defic Syndr, 1993. 6(5): p. 497-502.
74.de Vincenzi, I., A longitudinal study of human immunodeficiency virus transmission by heterosexual partners. European Study Group on Heterosexual Transmission of HIV. N Engl J Med, 1994. 331(6): p. 341-6.
75.Henn, M.R., C.L. Boutwell, P. Charlebois, et al., Whole Genome Deep Sequencing of HIV-1 Reveals the Impact of Early Minor Variants Upon Immune Recognition During Acute Infection. Plos Pathogens, 2012. 8(3).
76.Redd, A.D., C.E. Mullis, D. Serwadda, et al., The Rates of HIV Superinfection and Primary HIV Incidence in a General Population in Rakai, Uganda. Journal of Infectious Diseases, 2012. 206(2): p. 267-274.


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔