Mutations associated with antiviral drug resistance in hiv-1

Planinić, Ana (2014) Mutations associated with antiviral drug resistance in hiv-1. Doctoral thesis, Faculty of Science > Department of Biology.

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Abstract

The aim of this study was to: determine the prevalence of Human immunodeficiency virus type 1 (HIV-1) resistance to antiretroviral drugs in treatment-experienced patients using two methods (single-point analysis, cumulative model), the distribution of HIV subtypes, analyze frequency of clinicaly relevant resistance mutations, and to compare results of ultra-deep sequencing (UDS) with standard sequencing method on selected samples. The prevalence of resistance and viral subtypes were determined by analyzing HIV pol genomic region and by applying different resistance interpretation algorithms in persons with treatment failure in the period 2008-2012. Resistance mutations were detected in 50% of samples and the most frequent was M184V (26.7% of samples). The resistance to nucleoside analogues reverse transcriptase inhibitors was found in 39.5%, to non-nucleoside analogues reverse transcriptase inhibitors in 42% and to protease inhibitors in 5.8% of samples. The majority of patients were infected with HIV-1 subtype B (71%). No significant difference was found between two methods when estimating the prevalence of resistance to drugs. A total of 65 out of 85 (77.3%) mutations revealed by UDS were not identified by standard sequencing method. For the first time in Croatia, this study showed the prevalence of HIV-resistance to antiretroviral drugs in patients subjected to treatment and analyzed the patterns of mutations in an enviroment under drug presure. UDS identified minor drug-resistance variants which may be the reason of treatment failure and revealed additional information about genetic variability of the virus.

Item Type: Thesis (Doctoral thesis)
Keywords: HIV type 1, antiretroviral treatment, HIV-1 subtype, ultra-deep sequencing
Supervisor: Židovec Lepej, Snježana
Date: 2014
Number of Pages: 107
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Grozdana Sirotic
Date Deposited: 07 May 2014 12:03
Last Modified: 07 May 2014 12:03
URI: http://digre.pmf.unizg.hr/id/eprint/1056

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