Abstract

Widespread introduction of HIV integrase inhibitors into clinical care may result in appearance of drug resistance mutations affecting treatment outcome. The aim of our study was to monitor the resistance patterns of integrase inhibitors beside protease and reverse transcriptase inhibitors in newly diagnosed therapy-naive HIV-positive patients in Hungary between 2017 and 2019.Genotype-based resistance testing of HIV integrase, protease and reverse transcriptase was performed by amplification and Sanger population sequencing from plasma samples. Drug resistance mutations were identified by the algorithm of Stanford HIV Drug Resistance Database.Potentially transmitted, non-polymorphic integrase major mutation was detected in 1 out of 249 samples, while accessory mutations were observed in further 31 patients (12.4%). The overall prevalence of transmitted drug resistance (TDR) mutations related to protease and reverse transcriptase inhibitors was 5.8% (10/173) between the end of 2017 and 2019. Nucleoside reverse transcriptase inhibitor associated resistance mutations were the most frequent indicators of TDR (6/173; 3.5%), followed by resistance mutations associated with protease (3/173; 1.7%) and non-nucleoside reverse transcriptase inhibitors (2/173, 1.2%).The first detection of integrase major mutation and the changing patterns of other resistance mutations in Hungarian untreated HIV-positive population indicate the necessity of continuous molecular surveillance of Hungarian HIV epidemic.

Highlights

  • Combination antiretroviral therapy has reduced HIV-related morbidity and mortality significantly [1]

  • HIV-1 drug resistance analysis of 249 samples revealed a low prevalence of surveillance drug resistance mutations associated with integrase inhibitors in therapy-naive patients (Fig. 1/A)

  • Surveillance drug resistance mutations associated with PR or reverse transcriptase (RT) inhibitors were not detected among patients harbouring HIV-1 strains with major or accessory integrase resistance mutations

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Summary

Introduction

Combination antiretroviral therapy (cART) has reduced HIV-related morbidity and mortality significantly [1]. Effective cART reduces the risk of HIV transmission [3], the emergence of drug resistant variants in the presence of antiretroviral drugs can lead to incomplete viral suppression and therapeutic failure. Acta Microbiologica et Immunologica Hungarica 68 (2021) 2, 87–91 into the host genome. Due to their excellent tolerability, minimal toxicity, high efficacy and ease of use, integrase inhibitors became preferred agents for treatment-naive or experienced patients and serve as novel treatment options in case of acquired and transmitted resistance in combination with other HIV drug classes [5]. These drugs, with a higher genetic barrier to resistance, include dolutegravir (DTG), bictegravir (BIC) and cabotegravir (CAB); they were approved in Europe in 2014, 2018 and 2020, respectively [5, 6]

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