Standard and enhanced genotypic assessment of HIV drug resistance and tropism in subtype-B and non-subtype-B HIV-1 infections
department or school: Medicine, Faculty of
department or school: Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Lee, Guinevere Kwun Wing Queenie
issued: 2015-01-06T18:18:47Z
issued: 2014
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Sequencing human immunodeficiency virus type 1 (HIV-1) for drug resistance mutations and viral tropism is crucial to the current HIV/AIDS personalized treatment approach. This thesis addresses particular areas where clinical utility data is lacking: First, current methods were validated as clinically useful with plasma viral RNA primarily from patients infected with subtype B HIV-1, the dominant strain in developed countries; however, globally most patients are infected with non-subtype B variants. Secondly, there is insufficient data available with respect to the newest classes of antiretroviral drugs (i.e. CCR5-antagonist and integrase inhibitors). Finally, modern antiretroviral therapies often lead to “undetectable plasma viremia” (i.e. successful ongoing treatment) which make plasma-based genotypic testing impossible; the utility of examining alternative sample types is being actively explored. The overall objective of this thesis is to evaluate genotypic assessment of HIV-1 using standard and “second generation” DNA sequencing methods for guiding clinical decisions in nonconventional sample types. Specifically, it is hypothesized that genotypic assessment of subtype A, C and D HIV-1, plasma viral RNA collected pre-therapy, and viral DNA archived in blood cells are useful predictors of in vitro phenotype and/or clinical outcomes. Chapter 1 and 2 examine the clinical utility of current genotyping approaches when applied to non-subtype-B HIV-1. Results suggest that (1) transmitted genotypic drug resistance predicted small but negative treatment outcomes in non-B infections, and (2) current genotypic tools for predicting viral tropism had poor sensitivities and/or specificities in subtypes A and D, but not C HIV-1. Chapter 3 and 4 examine the clinical utility of current genotypic approaches coupled with alternative sample types. Results suggest that (3) pre-therapy plasma sample tropism results predicted post-therapy post-suppression tropism in 90% of subjects, and…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/51771
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has type: Thesis/Dissertation
date issued: 2015-02
is shown at: 10.14288/1.0135649
language: eng
degree discipline: Experimental Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivs 2.5 Canada
rights URI: http://creativecommons.org/licenses/by-nc-nd/2.5/ca/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/51771