Molecular and epidemiological monitoring of acquired HIV-1 drug resistance to integrase inhibitors in the Volga federal district in the period 2021–2024

Objective. To perform molecular genetic monitoring of HIV-1 drug resistance to integrase inhibitor (INIs) and to assess the prevalence of mutations associated with viral resistance to these drugs in the Volga Federal District (VFD) from 2021-2024. Materials and methods. The study analyzed 121 blood plasma samples from HIV-infected patients experiencing virological failure of antiretroviral therapy (ART) with integrase inhibitors. The samples were delivered for HIV-1 drug resistance testing from ten subjects of the Volga Federal District: the Republics of Bashkortostan, Mari El, Mordovia, Udmurtia and Chuvashia, and Kirov, Nizhny Novgorod, Penza, Saratov and Ulyanovsk oblasts. HIV-1 genotyping was performed by fragment sequencing of reverse transcriptase, protease, and integrase regions of the HIV-1 pol gene. Information about the samples was obtained from test requisition forms for HIV-1 drug resistance testing provided by the regional AIDS prevention and control centers of the Volga Federal District. Results. The number of HIV-infected patients receiving INIs-based antiretroviral therapies in VFD is increasing, reaching 22.1 % of all treated patients in 2023. The analysis of HIV-1 resistance to INIs revealed mutation combinations associated with resistance to second–generation INIs: R263RK, E138K+T66A+G118R, E138K+G140A+Q148R, E138K+G140A+S147G, S147G+N155H. The following risk factors for developing INIs resistance were determined: the HIV infection duration more than 15 years from the first positive Western blot result (p = 0.057), the age of HIV-infected patients over 35 years (p = 0.079), and existence of HIV-1 resistance to nucleoside reverse transcriptase (NRTIs), non-nucleoside reverse transcriptase (NNRTIs), or protease inhibitors (PIs) (p 0.0001). Conclusions. The growing proportion of HIV-infected patients receiving INIs-based antiretroviral therapies, including second–generation INIs, in the VFD underscores the necessity for regular molecular and genetic monitoring of HIV-1 resistance to INIs which is essential for further study of the prevalence of resistant viral strains to increase the effectiveness of ART.