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Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. 总被引:27,自引:1,他引:27
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T Shirasaka M F Kavlick T Ueno W Y Gao E Kojima M L Alcaide S Chokekijchai B M Roy E Arnold R Yarchoan et al. 《Proceedings of the National Academy of Sciences of the United States of America》1995,92(6):2398-2402
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Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids. 总被引:8,自引:0,他引:8
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Stefan G. Sarafianos Kalyan Das Arthur D. Clark Jr. Jianping Ding Paul L. Boyer Stephen H. Hughes Edward Arnold 《Proceedings of the National Academy of Sciences of the United States of America》1999,96(18):10027-10032
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OBJECTIVES: The aim of the study was to investigate the presence of M184I/V in minor HIV-1 populations of patients who failed lamivudine (3TC) and/or didanosine (ddI) treatment. MATERIALS AND METHODS: Fourteen 3TC-experienced patients who, after switching therapy to a ddI regimen, had a new failure without M184I/V in the major viral population were included in the study. Ninety plasma samples were analysed by direct sequencing and selective real-time polymerase chain reaction (SPCR), which detects GTG/GTA and ATA mutants down to 1 and 0.2% of the population, respectively. RESULTS: In five samples, SPCR detected resistant virus when direct sequencing detected wild-type M184. In patients with mixed viral populations at sequencing, the median proportion of mutants detected by SPCR was 30%. SPCRGTG reactivity dominated, while SPCRATA reactivity only was uncommon. M184I/V disappeared in patients in whom 3TC was stopped but ddI continued. Ten patients with ddI failure had no M184I/V. CONCLUSIONS: Minor HIV-1 strains may harbour M184I/V in patients failing ddI therapy, despite direct sequencing showing wild-type virus. Although M184I/V may reduce the genetic barrier of ddI for mutations such as K65R and L74V, the lack of re-emergence of M184I/V in the minor quasispecies of most patients who failed ddI suggests that M184I/V was not a preferred route to ddI resistance in our patient population. 相似文献
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Human immunodeficiency virus type 1 (HIV-1) strains selected for resistance against the HIV-1-specific [2'',5''-bis-O-(tert-butyldimethylsilyl)-3''-spiro- 5''''-(4''''-amino-1'''',2''''-oxathiole-2'''',2''''-dioxide)]-beta-D-pentofurano syl (TSAO) nucleoside analogues retain sensitivity to HIV-1-specific nonnucleoside inhibitors. 总被引:3,自引:1,他引:3
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J Balzarini A Karlsson A M Vandamme M J Pérez-Pérez H Zhang L Vrang B Oberg K B?ckbro T Unge A San-Félix et al. 《Proceedings of the National Academy of Sciences of the United States of America》1993,90(15):6952-6956
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Long-term follow-up of patients taking tenofovir DF with low-level HIV-1 viremia and the K65R substitution in HIV-1 RT 总被引:1,自引:0,他引:1
Patients with on-going HIV-1 replication and a K65R mutation in HIV-1 RT were assessed for further development of RT mutations while taking tenofovir disoproxil fumarate and other antiretroviral drugs. K65R was observed in 10 out of 536 treatment-experienced patients entering the study. K65R became undetectable in two patients, and the development of additional resistance mutations was minimal. Over 18 months, no patient developed multinucleoside resistance (Q151M or T69 insertions) and plasma viral loads were stable (median +0.04 log10 copies/ml). 相似文献
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