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Primarna odpornost virusa imunske pomanjkljivosti pri novoodkritih okuženih osebah v Sloveniji v letih 2017 in 2018
ID Govednik, Tea (Author), ID Poljak, Mario (Mentor) More about this mentor... This link opens in a new window

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Abstract
Drastičen napredek protiretrovirusnega zdravljenja je okužbo z virusom HIV pretvoril v obvladljivo kronično stanje. Kljub temu je uspešnost zdravljenja močno odvisna od razvoja z odpornostjo povezanih mutacij, ki v primeru prenosa med nezdravljenimi osebami, predstavljajo primarno odpornost virusa (angl. transmitted drug resistance, TDR). Glede na celokupno pojavnost TDR, evropske smernice priporočajo testiranje novoodkritih HIV-pozitivnih oseb na prisotnost TDR pred začetkom zdravljenja. V magistrski nalogi smo želeli določiti stopnjo TDR pri novoodkritih HIV-pozitivnih osebah v obdobju 2017–2018 v Sloveniji. V raziskavo smo vključili 57 vzorcev krvne plazme, po osamitvi nukleinske kisline in pomnoževanju odseka gena pol z zapisom za virusno proteazo, reverzno transkriptazo in/ali integrazo smo izvedli sekvenčno reakcijo in pridobili nukleotidno zaporedje, znotraj katerega smo iskali morebitne s TDR povezane nadzorne mutacije. Odkrili smo mutacijo K219Q pri eni osebi. S tem smo ocenili celokupno prevalenco TDR in prevalenco TDR iz skupine nukleozidnih zaviralcev reverzne transkriptaze na 1,8 %. Nadzornih mutacij TDR iz skupin zaviralcev proteaze in nenukleozidnih zaviralcev reverzne transkriptaze nismo odkrili. Podobno tudi v skupini zaviralcev integraze nismo določili pomembnejših mutacij povezanih z odpornostjo. S filogenetsko analizo smo določili 22 slovenskih filogenetskih skupin, prenosa odpornosti znotraj skupin nismo dokazali. Glede na ocenjeno prevalenco sklepamo, da testiranje virusa HIV na prisotnost TDR pred uvedbo zdravljenja v Sloveniji za vse novoodkrite osebe zaenkrat še ni potrebno, smiselno pa je nadaljnje spremljanje TDR.

Language:Slovenian
Keywords:humani virus imunske pomanjkljivosti, HIV, primarna odpornost, TDR, nadzorne mutacije, SDRM, protiretrovirusno zdravljenje
Work type:Master's thesis/paper
Typology:2.09 - Master's Thesis
Organization:BF - Biotechnical Faculty
Publisher:[T. Govednik]
Year:2020
PID:20.500.12556/RUL-113863 This link opens in a new window
UDC:578.7+578.5:578.828
COBISS.SI-ID:5170296 This link opens in a new window
Publication date in RUL:08.02.2020
Views:1612
Downloads:256
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Secondary language

Language:English
Title:Human immunodeficiency virus transmitted drug resistance among newly diagnosed patients in Slovenia in the years 2017 and 2018
Abstract:
Drastic improvement of antiretroviral therapy transformed HIV infection in a manageable chronic condition. However, treatment is strongly compromised with the development of drug resistance mutations, which can be transmitted among treatment naïve individuals as transmitted drug resistance (TDR). Based on the overall prevalence of TDR, European guidelines recommend resistance testing in newly diagnosed individuals prior to treatment initiation. The aim of our study was to determine the prevalence of TDR among newly diagnosed HIV-positive individuals in Slovenia in the years 2017 and 2018. We included 57 plasma samples; we extracted nucleic acids, amplified and sequenced partial protease and reverse transcriptase and/or integrase region of the HIV pol gene. Obtained sequences were analyzed for the presence of TDR mutations. Surveillance drug resistance mutation was found in one patient only (K219Q), corresponding to a prevalence of 1.8% TDR to nucleoside reverse transcriptase inhibitors as well as the overall TDR prevalence. Surveillance mutations conferring resistance to protease and non-nucleoside reverse transcriptase inhibitors were not detected. In addition, no major drug resistance mutations were found in the integrase region. Phylogenetic analysis revealed 22 Slovenian phylogenetic clusters with no observed transmission of TDR. Low prevalence of TDR indicates that no modification is necessary in the national strategy for resistance testing in newly diagnosed treatment naïve HIV-positive individuals; however, continuing surveillance of TDR is still needed.

Keywords:human immunodeficiency virus, HIV, transmitted drug resistance, TDR, surveillance drug resistance mutation, SDRM, antiretroviral therapy

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