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Analysis of HIV-1 genotypic mutations in patients with multiple virological failure

Sale, Rosa (2007) Analysis of HIV-1 genotypic mutations in patients with multiple virological failure. [Doctoral Thesis]



Background: Genotyping analysis during the course of antiretroviral treatment might provide significant informations that should be carefully considered as guidelines for rational therapeutic strategies. The genotypic analysis is generally limited to the amino acid positions that are known to be involved in drug resistance. In this study we tried to evaluate if a more complete resistance report will improve the strategy of the therapeutic choice. Methods: Our data are based on two consecutive genotypic resistance tests of 12 HIV-1 positives patients with an history of multiple failure, and on a new interpretation of the same tests following latest guide lines. Objective: to evaluate if the development of new resistance mutations in the second test was already observable in the research report of the previous test between the mutations in sites already known to be associated to a resistance . Results: Only in two patients some of silent mutations or other mutations in resistance sites, and only for the transcriptase gene, evolved in resistance mutation included in the report of second test. No significant differences were found between responders and non responders patients considering mutations in codons not known to be associated to a resistance. With the new interpretation it has been possible to determine that in all patients several resistance mutations toward Protease inhibitors appear in both new reports, that mutations seen in the first interpretation as polymorphisms in sites of non-resistance, or neutral mutations in resistance sites. The major discordances between the two interpretations have been observed in the first test for the NRTIs stavudine and tenofovir, and all non-responder patients except one were in therapy with stavudine and/or tenofovir at the time of the first test. Conclusion: Much more is to know about drug resistance than the canonical mutations identified, and some of the informations not included in the report might be more useful than what expected if better analyzed, even if they seems have no evidence of resistance.

Item Type:Doctoral Thesis
Date:27 November 2007
Tutor:Ortu, Francesco
PhD classes:Ciclo 20 > Sviluppo e sperimentazione dei farmaci antivirali
Coordinator:La Colla, Paolo
Institution:Universita' degli Studi di Cagliari
Divisions:Dipartimenti (fino a dicembre 2011) > Dipartimento di Scienze e tecnologie biomediche
Subjects:Area 05 - Scienze biologiche > BIO/19 Microbiologia generale
Uncontrolled Keywords:HIV-1, Genotyping analysis
ID Code:134
Deposited On:04 Nov 2008 10:14

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