Molekularna heterogenost virusa humane imunodeficijencije tipa 1 i uloga transmisijskih lanaca u lokalnom širenju infekcije u Hrvatskoj

doctoral thesis

• Title (english): Molecular diversity of human immunodeficiency virus type 1 and the role of transmission chains in the local spread of infection in Croatia
• Author: Maja Oroz
• Mentor: Josip Begovac (mentor)
• Mentor: Snježana Židovec-Lepej (komentor)
• Committee member: Tatjana Vilibić Čavlek (predsjednik povjerenstva)
• Committee member: Floriana Jakuš (član povjerenstva)
• Committee member: Alemka Markotić (član povjerenstva)
• Committee member: Branko Kolarić (član povjerenstva)
• Committee member: Adriana Vince (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2020-12-28, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Infectology
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Cilj ove doktorske disertacije bio je istražiti molekularnu epidemiologiju HIV-1 infekcije među prethodno neliječenim HIV-om zaraženim osobama iz Hrvatske. U istraživanje je uključeno 403 ispitanika, odnosno 92,4% svih HIV-om zaraženih osoba koje su ušle u kliničku skrb u Hrvatskoj tijekom vremenskog perioda od 2014. do 2017. godine. Prevalencija primarne rezistencije HIV-1 na inhibitore reverzne transkriptaze (RTI), proteaze (PI) i integraze (InSTI) analizirana je tehnologijom sekvenciranja po Sangeru. Ukupna prevalencija primarne rezistencije na antiretrovirusnu terapiju (ART) iznosila je 16,4%. Prevalencija rezistencija prema pojedinim klasama lijekova, nukleozidnim RTI (NRTI), nenukleozidnim RTI (NNRTI), PI i InSTI iznosila je 11,4%, 6,7%, 2,5% i 1%. U istraživanju je utvrđena i primarna rezistencija na tri klase lijekova kod 2,2% ispitanika. Uz to, 48 ispitanika je nasumično odabrano za analizu mutacija povezanih s primarnom rezistencijom na ART pomoću tehnologije sekvenciranja nove generacije, a dodatne mutacije su pronađene u 6 uzoraka. Filogenetska analiza pokazala je visok postotak klasteriranja (347/403, 86,1%) i identificirala aktivno širenje više mutacija povezanih s rezistencijom u Hrvatskoj, čak i širenje rezistencije na tri klase lijekova. Najveći klaster s mutacijom povezanom s primarnom rezistencijom na ART bio je T215S klaster, formiran od 53 ispitanika, a filodinamičkom analizom je njegov razvoj procijenjen u 1992. godini. Rezultati ove studije ukazuju na kontinuiranu potrebu za nadziranjem primarne rezistencije HIV-1 i razvoja transmisijskih klastera u Hrvatskoj.

Abstract (english)

The aim of this study was to investigate the molecular epidemiology of HIV-1 infection in treatment-naive HIV-1 infected persons from Croatia. Study included 403 persons, representing 92,4% of all HIV-1 positive individuals entering clinical care in Croatia in 2014-2017. The prevalence of transmitted drug resistance (TDR) to reverse transcriptase inhibitors (RTI), protease inhibitors (PI) and integrase strand-transfer inhibitors (InSTI) was assesed by Sanger sequencing. Overall prevalence of TDR was 16,4%. According to drug classes, resistance to nucleoside RTI (NRTI), non-nucleoside RTI (NNRTI), PI and InSTI was found in 11,4%, 6,7%, 2,5% and 1% of individuals, respectively. Triple-class resistance was determined in 2,2% of individuals. In addition, 48 individuals were randomly selected for next generation sequencing and additional TDR mutations were detected in 6 samples. Phylogenetic analysis showed high rate of clustering (347/403, 86,1%) and identified forward transmission of multiple TDR mutations in Croatia, even that of triple-class resistance. The largest cluster harbouring TDR consisted of 53 persons with T215S mutation and phylodinamic analysis estimated to originate in the year 1992. This data shows a continuing need for pre-treatment HIV-1 resistance testing and surveillance of local transmission networks in Croatia.

• Keywords: HIV-1; molekularna epidemiologija; primarna rezistencija HIV-1; transmisijski klasteri; sekvenciranje tehnologijom nove generacije
• Keywords (english): HIV-1; molecular epidemiology; HIV-1 primary resistance; transmission clusters; next-generation sequencing
• Language: croatian
• URN:NBN: urn:nbn:hr:105:291812
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Catalog URL: https://katalog.nsk.hr/F/19IT7Y755V1NXQJPHCLYSQGPF6BLAPPF179HQ7FAXXMYBYGMV5-36292?func=find-e&request=Molekularna+heterogenost+virusa+humane+imunodeficijencije+tipa+1+i+uloga+transmisijskih+lanaca+u+lokalnom+%C5%A1irenju+infekcije+u+Hrvatskoj&find_scan_code=FIND_NAS&adjacent=N&local_base=MF_WEB&x=0&y=0&filter_code_1=WLN&filter_request_1=&filter_code_2=WYR&filter_request_2=&filter_code_3=WYR&filter_request_3=&filter_code_4=WFM&filter_request_4=
• Type of resource: Text
• Extent: 130 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-03-24 12:42:32