Rezistencija HIV1 virusa na 3 klase lijekova: prvi slučaj

Resistance of Human Immunodeficiency Virus (HIV) to antiretroviral drugs is an important limitation in achieving complete suppression of viral replication and therefore represents an important clinical issue. It refers especially to therapy-naive individuals infected with resistant HIV strains, e.g. individuals with transmitted drug resistance (TDR). Transmitted drug resistance mutations (TDRMs) are clinically relevant and may reduce the efficacy of antiretroviral therapy. In this paper, we report the first case of HIV-1 transmitted triple-class drug resistance in Croatia. The aim of this study was to characterize drug resistance patterns and TDRMs in the newly diagnosed, treatment-naive HIV-1 patient with such a complex resistance pattern. Sanger sequencing (SS) of the sample showed four reverse transcriptase inhibitor (RTI) resistance mutations (E44D, T215E, K103N, L100I) affecting two drug classes and two protease inhibitor resistance mutations (V32I, I47V). To characterize HIV-1 minority drug resistance variants below the detection limit of SS, deep sequencing (DS) analysis was performed. DS analysis identified the same triple class resis- tance pattern that was identified by SS with addition of several other RTI mutations. The patient described in this report is the first patient with HIV-1 triple-class resistance in Croatia and further studies will be directed toward analysing possible local onward transmission of this resistant virus.
Rezistencija virusa humane imunodeficijencije (HIV) na antiretrovirusne lijekove sprječava supresiju virusne replikacije te predstavlja značajan izazov u kliničkoj medicini. Posebno valja istaknuti problem primarne rezistencije (engl. transmitted drug resistance, TDR) koja se odnosi na prethodno neliječene osobe koje su zaražene rezistentnim sojevima HIV-a. Mutacije koje su pov- ezane s primarnom rezistencijom (engl. transmitted drug resistant mutations, TDRM) su klinički značajne i mogu nepovoljno djelovati na učinkovitost antiretrovirusnog liječenja. U ovom je radu opisana prva osoba s primarnom rezistencijom HIV-a na 3 klase antiretrovirusnih lijekova u Hr- vatskoj. Cilj ovog istraživanja bio je analizirati obrasce primarne rezistencije i TDRM u novodi- jagnosticiranog i neliječenog HIV-om zaraženog pojedinca. Primjenom Sangerovog sekvenciranja (SS) dokazali smo četiri mutacije povezane s rezistencijom na inhibitore reverzne transkriptaze (E44D, T215E, K103N, L100I) koje smanjuju osjetljivost na dvije klase lijekova (nukleozidne analoge inhibitore reverzne transkriptaze i nenukleozidne inhibitore reverzne transkriptaze) kao i dvije mutacije (V32I, I47V) povezane s rezistencijom na inhibitore proteaze. U svrhu identifikacije mogućeg postojanja manjinskih rezistentnih varijante ispod granice detekcije SS-a, provedena je analiza dubinskim sekvenciranjem (DS). DS analiza identificirala je isti obrazac rezistencije na 3 klase antiretrovirusnih lijekova identificiran s SS uz nekoliko dodatnih mutacija. U ovom je radu opisan prvi slučaj primarne rezistencije HIV-a na 3 klase antiretrovirusnih lijekova, a buduća istraživanja analizirat će moguće putove transmisije ovog rezistentnog virusa u Hrvatskoj.