Prevalence of drug resistance mutations against dolutegravir, lamivudine, and rilpivirine in ART-naïve residents of South-East Austria

Abstract

Background: Although a lot of progress has been made regarding antiretroviral therapy, no cure for HIV has been found and lifelong treatment is needed. Long-term drug exposure is accompanied by various side effects and toxicities. With the successful introduction of two-drug regimens in recent years, lowered cumulative drug exposure while maintaining viral suppression has been made possible. Objectives: To ensure successful treatment, anti-retroviral therapy (ART) should ideally start as soon as possible after HIV-1 diagnosis. In order to guarantee high efficacy of initial combination regimens, data on local prevalence of drug resistance mutations is of great importance. The aim of this project was to identify transmitted HIV-1 drug resistance mutations (DRMs) against drugs currently recommended for two-drug regimes, dolutegravir (DTG), lamivudine (3TC), and rilpivirine (RPV). In addition, the local transmission network of HIV-1 in South-East Austria was reconstructed. Material and Methods: In this study, 192 HIV patients who had been diagnosed between 2013-2018 living in South-East Austria were included. Conventional Sanger sequencing analysis was performed and sequences were analyzed for DRMs including DTG, 3TC, and RPV. Molecular network analysis was carried out to determine presumed relations and to identify shared DRMs. Results and Conclusion: Of all ART-naïve patients, 16% showed clinically relevant DRMs against DTG, 3TC, and/or RPV. The prevalence of these DRMs was significantly higher in genetic transmission clusters when compared to non-genetically linked individuals. Within clusters, the majority of DRMs were shared, indicating an elevated risk of transmission of resistant HIV-1 strains. However, of all patients with clinically relevant DRMs, only 2% were not eligible for at least one of the currently suggested two-drug regimens.

Date of Award	2022
Original language	English
Awarding Institution	Medical University Graz
Supervisor	Harald Kessler (Supervisor) & Evelyn Stelzl (Co-supervisor)