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dc.contributor.authorVesterås, Kim Jonas
dc.date.accessioned2018-07-08T22:01:27Z
dc.date.available2018-07-08T22:01:27Z
dc.date.issued2018
dc.identifier.citationVesterås, Kim Jonas. Resistens mot integrasehemmere ved behandling av HIV-1 infeksjon i Norge. Master thesis, University of Oslo, 2018
dc.identifier.urihttp://hdl.handle.net/10852/62129
dc.description.abstractnob
dc.description.abstractABSTRACT BACKGROUND: Integrase strand transfer inhibitors (INSTI) are antiretroviral drugs that are used as part of combination therapy in the treatment of HIV-infection. Analysis for drug resistance against INSTI was established in Norway in 2007. There are currently three available drugs in the class: raltegravir (RAL), elvitegravir (EVG), and dolutegravir (DTG). OBJECTIVE: The aim of this study was to determine the prevalence of drug resistance mutations associated with reduced susceptibility for INSTI. Furthermore, we wanted to investigate whether our findings support the current Norwegian recommendations on treatment with INSTI. DESIGN: Retrospective observational study. METHODS: We investigated the results from 165 genotypic resistance tests of the integrase gene. The inclusion period was from January 1st 2009 to September 30th 2016. The test material originated from HIV-1 patients with treatment failure, and who were currently or previously exposed to INSTI. Genotypic resistance was defined as the presence of combinations of mutations classified as low level resistance or more severe, according to Stanford HIV Drug Resistance Algorithm v.8.4. RESULTS: Among the 165 tests which were analyzed, 78.8 % (n=130) of the viral strains were found to be susceptible to all INSTI. Mutations associated with reduced susceptibility to RAL, EVG and DTG were found in 21.1 %, 19.9 %, and 8.4 % of the cases, respectively. 94.3 % of the tests with resistance mutations against RAL also had resistance mutations against EVG, while 42.4 % of the tests with resistance mutations against EVG also had resistance mutations against DTG. The most common mutations observed were localized in position N155 (n=17), Q148 (n=12), G140 (n=9) and Y143 (n=5). The most frequent mutations associated with genotypic resistance for DTG were in position Q148. For DTG, the genotypic resistance consisted of 1 sample with high level resistance, 11 samples with intermediate resistance and 2 samples with low level resistance. CONCLUSION: Resistance mutations were found in a relatively small fraction of the analyzed samples, suggesting that resistance against INSTI is infrequent in Norway. Our results also showed lower prevalence of genotypic resistance to DTG than to EVG or RAL. This is in accordance with other data showing that DTG has a high genetic barrier, and highlights DTG as a more suitable primary treatment than the other INSTI drugs currently on the market.eng
dc.language.isonob
dc.subject
dc.titleResistens mot integrasehemmere ved behandling av HIV-1 infeksjon i Norgenob
dc.title.alternativeResistance to Integrase Strand Transfer Inhibitors (INSTI) among INSTI-experienced HIV-1 patients in Norwayeng
dc.typeMaster thesis
dc.typeGroup thesis
dc.date.updated2018-07-08T22:01:27Z
dc.creator.authorVesterås, Kim Jonas
dc.identifier.urnURN:NBN:no-64720
dc.type.documentProsjektoppgave
dc.type.documentGruppeoppgave
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/62129/1/Resistens-mot-integrasehemmere-ved-behandling-av-HIV-1-infeksjon-i-Norge.pdf


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